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Lin S, Xu Z, Lin Z, Xie B, Feng J. Advances in pathogenesis and treatment of ocular involvement in Behcet's disease. Front Immunol 2023; 14:1206959. [PMID: 37841268 PMCID: PMC10570607 DOI: 10.3389/fimmu.2023.1206959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 09/08/2023] [Indexed: 10/17/2023] Open
Abstract
Behcet's disease (BD) is a chronic multi-systemic disease characterized by relapsing-remitting oral ulcers, genital ulcers, ocular inflammatory involvements, and numerous other systemic features. Ocular involvements are quite common in BD and may cause severe tissue damage and potentially blindness. Even though the pathogenesis of BD remains ambiguous, growing evidences have shown that genetic factors, environmental triggers and immunological abnormalities play significant roles in its development and progression. Novel biotherapies targeting IFN-γ, TNF-α and interleukins have been used in recent years. In this review, we mainly pay attention to the ocular involvement of BD, and discuss the current understanding of mechanisms and advances in therapeutic approaches, especially novel biologics. Finally, we discuss the management in patients with pregnancy.
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Affiliation(s)
- Suibin Lin
- Department of Gynaecology and Obstetrics, Zhangpu Hospital, Zhangzhou, China
| | - Zhirong Xu
- Department of Internal Medicine, Zhangpu Hospital, Zhangzhou, China
| | - Zhiming Lin
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Baozhao Xie
- Department of Rheumatology and Immunology, the Seventh Affiliated Hospital of Guangxi Medical University (Wuzhou Gongren Hospital), Wuzhou, China
| | - Junmei Feng
- Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Rheumatology and Immunology, Nanfang Hospital of Southern Medical University, Guangzhou, China
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Ghaffari Laleh M, Bonyadi M, Shahriyari E, Jabbarpoor Bonyadi MH, Soheilian M, Yaseri M. Lack of Association between Monocyte Chemoattractant Protein-1 (MCP-1) Gene Promoter Polymorphism and Behcet's Disease with and without Ocular Involvement in Iranian Population: A Case-Control Study. Curr Eye Res 2021; 47:312-316. [PMID: 34459335 DOI: 10.1080/02713683.2021.1963785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
PURPOSE This case-control study aimed to evaluate the possible association of MCP-1 - 2518A/G genetic polymorphism with Behcet's disease (BD) in the Iranian patients. MATERIALS AND METHODS This study was performed in 135 Behcet's patients (51 ocular and 84 non-ocular) and 79 healthy individuals. Peripheral blood samples were genotyped for MCP-1 - 2518A/G using the PCR-RFLP technique. RESULTS The statistical analysis of MCP-1 - 2518A/G showed no significant differences in genotype/allele frequencies between Behcet's patients and controls. There was no significant association in genotype/allele frequencies between either ocular or non-ocular BD patients and controls. Also, different genotype/allele frequencies between ocular and non-ocular BD were not statistically significant. CONCLUSIONS In this study, with a threshold P-value of 0.05 and an estimated power of 0.81 to detect a significant association (odds ratio ≥1.2), we did not observe any association of this variant with Behcet's disease.
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Affiliation(s)
- Maryam Ghaffari Laleh
- Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran
| | - Mortaza Bonyadi
- Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran
| | - Elham Shahriyari
- Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran
| | | | - Masoud Soheilian
- Ocular Tissue Engineering Research Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Yaseri
- Department of Biostatistics and Epidemiology, Tehran University of Medical Sciences, Tehran, Iran
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Yan J, Yan Y, Young A, Yan Z, Yan Z. Effectiveness and Safety of Chinese Medicine Decoctions for Behcet's Disease: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:8202512. [PMID: 34335839 PMCID: PMC8313333 DOI: 10.1155/2021/8202512] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 06/22/2021] [Accepted: 07/03/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Behcet's disease (BD) is an autoimmune disease of systemic vasculitis with an unclear pathogenesis. Although western medicines remain the mainstay interventions, effectiveness and safety are significant challenges. Complementary and alternative medicine, including herbal medicine, are gaining more attention. Chinese medicine decoctions, which have been used for centuries, are the most common form of traditional therapies. OBJECTIVE The purpose of the review was to evaluate the effectiveness and safety of Chinese medicine decoctions in the treatment of BD. METHODS Randomized controlled trials (RCTs) for BD treatment with Chinese medicine decoctions were searched in six electronic databases until March 2021. Primary outcomes were total effective rate, recovery rate, and recurrence rate. Secondary outcomes were clinical feature scores (oral ulcers, eye lesions, genital ulcers, skin lesions, arthropathies, fever, and pathergy reactions) and laboratory index levels (erythrocyte sedimentation rate, C-reactive protein, and immunoglobulin A). The risk of bias was assessed with the Cochrane Handbook, and a meta-analysis was performed with RevMan 5.4.1. RESULTS Sixteen RCTs with 924 patients were included in the review. The meta-analysis indicated that Chinese medicine decoctions were effective for BD when compared with control groups for all the primary outcomes and 7/10 of the secondary outcomes. Adverse events were reported in 11 of the 16 RCTs, with the Chinese medicine decoctions possibly having fewer adverse events than western drugs. This review included a range of classical prescriptions. An additional meta-analysis of modified Gancao Xiexin Decoction for BD treatment was conducted. Gancao Xiexin decoction is also discussed as a representative prescription, as well as high-frequency herbs, and warrants further exploration for individualized medicine and pharmacology. CONCLUSION Chinese medicine decoctions have the potential to be effective and safe for treating BD. However, additional well-designed RCTs are needed to confirm the findings because of the unsatisfactory quality of the included studies.
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Affiliation(s)
- Jingxian Yan
- Chinese Medical College, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yi Yan
- Xinglin College, Liaoning University of Traditional Chinese Medicine, Shenyang 110167, China
| | - Andrew Young
- Department of Diagnostic Sciences, Arthur Dugoni School of Dentistry, University of the Pacific, Stockton, CA, USA
| | - Zhiyong Yan
- Department of Surgery, Handan First Hospital, Handan 056000, China
| | - Zhimin Yan
- Department of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing 100081, China
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Shaat RM, El Meadawy S, Rizk EM, Elgawad MSA, Elsaid TO. The significance of α-defensins 1-3 in Behcet’s disease: a case-control study among Egyptian patients. EGYPTIAN RHEUMATOLOGY AND REHABILITATION 2020. [DOI: 10.1186/s43166-020-00026-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Behcet’s disease (BD) is associated with uveitis, oral ulcers, genital ulcers and arthritis. Enhanced activity of innate immunity components, such as neutrophils, natural killer (NK) cells and endothelial cells, is a prominent feature of BD. The aim of this study was to clarify the significance of α-defensins 1-3 in BD and detect their correlation with disease activity, severity and oral ulcer activity.
Results
Significant differences were found between Behcet’s patients and controls as regards serum α-defensins 1-3 (median 10.1, IQR 4–45 μg/ml versus median 7.4, IQR 0.6–13.2 μg/ml, p = 0.001) and salivary α-defensins 1-3 (median 17.4, IQR 5.7–44 μg/ml versus median 8.6, IQR 3.3–11 μg/ml, p < 0.001). Receiver operating characteristic (ROC) showed a fair area under curve (AUC) (AUC = 0.743), with sensitivity of 40% and specificity 100% at cutoff value of 17.3 μg/ml for serum α-defensins 1-3, while salivary α-defensins 1-3 showed excellent AUC (AUC = 0.936), with sensitivity of 93.3% and specificity of 86.7% at cutoff value of 9.8 μg/ml. The levels of serum and salivary α-defensins 1-3 > cutoff value were significantly higher in active severe Behcet’s patients with active oral ulcers (p < 0.001).
Conclusion
α-Defensins 1-3 may be involved in the pathogenesis of BD and could be valuable markers in the determination of disease activity, severity and oral ulcer activity.
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Balbaba M, Ulaş F, Postacı SA, Öz B, Aydın S. Serum Cortistatin Levels in Patients with Ocular Active and Ocular Inactive Behçet Disease. Ocul Immunol Inflamm 2020; 28:601-605. [PMID: 31314641 DOI: 10.1080/09273948.2019.1610461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE To evaluate serum cortistatin (CST) levels in patients with ocular active and ocular inactive Behçet disease (BD) and its relationship with disease activity. METHODS 24 BD patients with ocular active, 24 BD patients with ocular inactive patients and 24 healthy control subjects were included in the study. RESULTS In ocular active and ocular inactive BD patients and healthy control subjects, the mean serum CST levels were 4.38 ± 1.63ng/ml, 5.46 ± 1.81ng/ml and 7.56 ± 1.73ng/ml, respectively. ESR, serum CRP, CST levels and NLR were significantly different between the groups (p < 0.001 for all). The CST levels were similar between ocular active and inactive BD patient groups (p = 0.197). ESR, CRP and NLR were significantly higher in ocular active BD patients compared to ocular inactive BD patients and healthy control subjects (p < 0.05 for all). CONCLUSION Serum CST level was significantly lower in BD patients. CST may be a neuropeptide that plays a role in the pathogenesis of BD.
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Affiliation(s)
- Mehmet Balbaba
- Faculty of Medicine, Department of Ophthalmology, Fırat University , Elazığ, Turkey
| | - Fatih Ulaş
- Faculty of Medicine, Department of Ophthalmology, Abant Izzet Baysal University , Bolu, Turkey
| | - Sevinç Arzu Postacı
- Faculty of Medicine, Department of Ophthalmology, Fırat University , Elazığ, Turkey
| | - Burak Öz
- Faculty of Medicine, Department of Rheumatology, Fırat University , Elazığ, Turkey
| | - Süleyman Aydın
- Faculty of Medicine, Department of Biochemistry, Fırat University , Elazığ, Turkey
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Mendes-Frias A, Santos-Lima B, Furtado DZS, Ruperez FJ, Assunção NA, Matias MJ, Gomes V, Gaifem J, Barbas C, Castro AG, Capela C, Silvestre R. Dysregulation of glycerophospholipid metabolism during Behçet's disease contributes to a pro-inflammatory phenotype of circulating monocytes. J Transl Autoimmun 2020; 3:100056. [PMID: 32743536 PMCID: PMC7388368 DOI: 10.1016/j.jtauto.2020.100056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 05/04/2020] [Indexed: 12/15/2022] Open
Abstract
Behçet's disease (BD) is a relapsing, multisystem and inflammatory condition characterized by systemic vasculitis of small and large vessels. Although the etiopathogenesis of BD remains unknown, immune-mediated mechanisms play a major role in the development of the disease. BD patients present leukocyte infiltration in the mucocutaneous lesions as well as neutrophil hyperactivation. In contrast to neutrophils, whose involvement in the pathogenesis of BD has been extensively studied, the biology of monocytes during BD is less well known. In this study, we analyzed the phenotype and function of circulating monocytes of 38 BD patients from Hospital of Braga. In addition, we evaluated the impact of inflammatory and metabolomic plasma environment on monocyte biology. We observed a worsening of mitochondrial function, with lower mitochondrial mass and increased ROS production, on circulating monocytes of BD patients. Incubation of monocytes from healthy donors with the plasma of BD patients mimicked the observed phenotype, strongly suggesting the involvement of serum mediators. BD patients, regardless of their symptoms, had higher serum pro-inflammatory TNF-α and IP-10 levels and IL-1β/IL-1RA ratio. Untargeted metabolomic analysis identified a dysregulation of glycerophospholipid metabolism on BD patients, where a significant reduction of phospholipids was observed concomitantly with an increase of lysophospholipids and fatty acids. These observations converged to an enhanced phospholipase A2 (PLA2) activation. Indeed, inhibition of PLA2 with dexamethasone or the downstream cyclooxygenase (COX) enzyme with ibuprofen was able to significantly revert the mitochondrial dysfunction observed on monocytes of BD patients. Our results show that the plasma inflammatory environment coupled with a dysregulation of glycerophospholipid metabolism in BD patients contribute to a dysfunction of circulating monocytes.
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Affiliation(s)
- Ana Mendes-Frias
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Bruno Santos-Lima
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Danielle Zildeana Sousa Furtado
- Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, 28660, Madrid, Spain
- Laboratório de Radicais Livres em Sistemas Biológicos e Bioanalítica, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Brazil
| | - Francisco J. Ruperez
- Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, 28660, Madrid, Spain
| | - Nilson Antonio Assunção
- Laboratório de Radicais Livres em Sistemas Biológicos e Bioanalítica, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Brazil
| | - Maria João Matias
- Autoimmune Disease Unit, Department of Internal Medicine, Hospital of Braga, Braga, Portugal
- Clinical Academic Center-Braga, Braga, Portugal
| | - Vânia Gomes
- Autoimmune Disease Unit, Department of Internal Medicine, Hospital of Braga, Braga, Portugal
- Clinical Academic Center-Braga, Braga, Portugal
| | - Joana Gaifem
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Coral Barbas
- Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, 28660, Madrid, Spain
| | - António Gil Castro
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - Carlos Capela
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga, Guimarães, Portugal
- Autoimmune Disease Unit, Department of Internal Medicine, Hospital of Braga, Braga, Portugal
- Clinical Academic Center-Braga, Braga, Portugal
| | - Ricardo Silvestre
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga, Guimarães, Portugal
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Sun F, Cao H, Wang F, Cao G. Behçet's disease with invasive pulmonary aspergillosis and Aspergillus auriculatus infection: A case report. Medicine (Baltimore) 2020; 99:e18938. [PMID: 32028403 PMCID: PMC7015660 DOI: 10.1097/md.0000000000018938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
RATIONALE Behçet's disease (BD) is an inflammatory disease that leads to multisystemic immune dysfunction and that involves pulmonary system alterations. PATIENT CONCERNS A 26-year-old woman presented with dull right chest pain for 30 days and intermittent cough with expectoration for 5 days. She had a history of recurrent oral ulcer and constitutional rash 2 months prior. DIAGNOSES The patient was diagnosed with BD complicated by IPA and Aspergillus auriculatus infection. INTERVENTIONS The patient was administered itraconazole oral solution (200 mg b.i.d) to treat the fungal infection. After a diagnosis of BD was made, she received 40 mg of methylprednisolone sodium succinate daily for 1 week.Then, she also received 24 mg of methylprednisolone sodium succinate daily, which was decreased by 2 mg per half month, until the rash had resolved. The patient continued to receive 200 mg Q. D itraconazole orally for 3 months. Thereafter, itraconazole was stopped, while daily oral administration of 10 mg of methylprednisolone sodium succinate was continued. OUTCOMES The rash was observed to resolve, and CT revealed that the lesions in both the right and left lung were reduced. During a telephone follow-up performed after 6 months, the patient stated that no symptoms had recurred during the follow-up period. LESSONS This case illustrates that for patients with BD, ignoring extrapulmonary symptoms often leads to a delayed diagnosis. Physicians should perform a thorough medical history and physical examination of these patients, as the information obtained in this manner may provide important clues for disease diagnosis and treatment.
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Affiliation(s)
| | - Hui Cao
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China
| | - Fan Wang
- Department of Respiratory Disease
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Yıldız M, Köker O, Adrovic A, Şahin S, Barut K, Kasapçopur Ö. Pediatric Behçet's disease - clinical aspects and current concepts. Eur J Rheumatol 2020; 7:S38-S47. [PMID: 31556871 PMCID: PMC7004268 DOI: 10.5152/eurjrheum.2019.19121] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 07/30/2019] [Indexed: 12/14/2022] Open
Abstract
Behçet's Disease was first described by a Turkish dermatologist, Hulusi Behçet, in 1937 as a triple symptom complex; aphthous stomatitis, genital ulcers, and uveitis. Today, in light of current trials and experiments, we know that the disease may have a wider involvement with a multisystemic recurrent course, causing significant morbidity and mortality. However, there are still unanswered questions, particularly about Pediatric Behçet's Disease. Although several immunological and genetic associations have been demonstrated, the real etiologic mechanism of the disease is unclear. The diagnosis is difficult due to its rarity in childhood, the lack of validation of the diagnostic criteria obtained from adult studies, and the inadequacy of large case-controlled studies. Also, the management is challenging and controversial due to the various geographic distribution of clinical spectrum. New therapeutic options under development in light of pathogenetic hypothesis seem to be promising.
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Affiliation(s)
- Mehmet Yıldız
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Oya Köker
- Department of Pediatric Rheumatology, İstanbul University, İstanbul School of Medicine, İstanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Sezgin Şahin
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Özgür Kasapçopur
- Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
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Russo FY, Ralli M, De Seta D, Mancini P, Lambiase A, Artico M, de Vincentiis M, Greco A. Autoimmune vertigo: an update on vestibular disorders associated with autoimmune mechanisms. Immunol Res 2019; 66:675-685. [PMID: 30270399 DOI: 10.1007/s12026-018-9023-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The role of the immune system in mediating cochleovestibular pathologies has received increasing attention in recent years. Autoimmune vertigo may be an invalidating condition and may worsen the quality of life of affected patients, especially in the cases of delayed diagnosis. Since the etiopathogenesis is still not clear, also the treatment is not yet completely delineated. According to the clinical presentation, autoimmune vertigo can present as an isolated disorder or in association with systemic autoimmune diseases. The main feature in autoimmune vertigo is the presence of an abnormal immune response, in either absence or presence of systemic autoimmune disease, directed against delicate components of the inner ear. This may determine a functional or anatomical alteration, with an inflammatory reaction often devastating for hearing and balance. Being the exact pathogenesis unknown, the diagnosis of autoimmune vertigo is based either on clinical criteria or on a positive response to steroids. The earlier the diagnosis is made, the sooner the therapy can be installed, giving a chance to the recovery of inner ear damages. Corticosteroids represent the most effective and universally accepted treatment, even if other immunomodulatory drugs are now having a more extensive use. HIGHLIGHTS: Vertigo is relatively frequent in autoimmune diseases; however, it is often misdiagnosed or attributed to central nervous system alterations rather to specific inner ear involvement. Vertigo and other audiovestibular symptoms may be the first manifestation of an autoimmune disease and if correctly addressed could significantly contribute to early diagnosis of the underlying autoimmune disease. Early diagnosis of immune-related vertigo can lead to prompt initiation of targeted therapy with elevate chances of preventing irreversible damages to the inner ear. The presence of alternating phases of well-being and disabling symptoms in patients with vertigo should always been considered, as they could suggest an underlying autoimmune condition.
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Affiliation(s)
- Francesca Yoshie Russo
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Massimo Ralli
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Daniele De Seta
- Department of Oral and Maxillo-facial Surgery, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy.
| | - Patrizia Mancini
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Alessandro Lambiase
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Marco Artico
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Marco de Vincentiis
- Department of Oral and Maxillo-facial Surgery, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Antonio Greco
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
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Yalçindag N, Köse HC. Comparison of the Treatment Results for Behçet Uveitis in Patients Treated with Infliximab and Interferon. Ocul Immunol Inflamm 2019; 28:305-314. [PMID: 31268743 DOI: 10.1080/09273948.2019.1606256] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose: To compare the efficacy and safety of infliximab and interferon in patients with refractory Behçet uveitis.Methods: Medical records of 20 patients treated with infliximab (IFX) and 33 patients treated with interferon (IFN) were retrospectively analyzed by evaluating the number of uveitis attacks, visual acuity and ocular inflammation at 6 and 12 months after initiation of treatment.Results: Mean duration of treatment was 22 ± 18 months in IFX group and 30.3 ± 22.5 months in IFN group. Sixteen patients of IFX group (80%) and 28 patients of IFN group (85%) achieved remission. In both groups, the mean best-corrected visual acuity and all inflammatory parameters improved. In terms of these parameters, there was no significant difference between the two groups.Conclusion: Infliximab and interferon improve control of ocular inflammation and efficiently decrease the relapse rate. Our results determined no significant difference between two agents in controlling intraocular inflammation.
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Affiliation(s)
- Nilüfer Yalçindag
- Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Helin Ceren Köse
- Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey
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11
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Nieto IG, Alabau JLC. Immunopathogenesis of Behçet Disease. Curr Rheumatol Rev 2019; 16:12-20. [PMID: 30987569 DOI: 10.2174/1573397115666190415142426] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 04/02/2019] [Accepted: 04/04/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Behçet's Disease (BD, OMIM 109650) is a chronic relapsing inflammatory disease of unknown etiology with unpredictable exacerbations and remissions. First described in 1937 by the Turkish dermatologist HulusiBehçet, as a trisympton complex (oral and genital ulcers and uveitis), it is now recognized as a multisystemic disease. The syndrome can manifest in diverse ways and can involve nearly every organ system. Several studies have implicated T cells and monocytes in the pathogenesis of BD especially when these cells are stimulated by heat shock proteins and streptococcal antigen. This article presents a review of the relevant published literature about the immunopathogenesis of BD. RESULT The authors used MeSH terms "Behçet's disease" with "pathophysiology," "pathogenesis," "genetic", "epigenetic", "immunogenetic" or "immune response" to search the PubMed database. All the relevant studies identified were included.
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Affiliation(s)
- Israel Gañán Nieto
- Department of Immunology. Hospital Universitario Ramon y Cajal, Ctra. Colmenar Viejo, Km 9,100. C.P. 28034. Madrid, Spain
| | - José Luis Castañer Alabau
- Department of Immunology. Hospital Universitario Ramon y Cajal, Ctra. Colmenar Viejo, Km 9,100. C.P. 28034. Madrid, Spain
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12
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Reduced Risk of BK Polyomavirus Infection in HLA-B51–positive Kidney Transplant Recipients. Transplantation 2019; 103:604-612. [DOI: 10.1097/tp.0000000000002376] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Karaca I, Palamar M, Guven Yilmaz S, Ates H. Evaluation of Ocular Surface and Meibomian Glands Alterations with Meibography in Patients with Inactive Behçet’s Uveitis. Curr Eye Res 2018; 44:356-359. [DOI: 10.1080/02713683.2018.1555261] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Irmak Karaca
- Department of Ophthalmology, Ege University School of Medicine, Izmir, Turkey
| | - Melis Palamar
- Department of Ophthalmology, Ege University School of Medicine, Izmir, Turkey
| | - Suzan Guven Yilmaz
- Department of Ophthalmology, Ege University School of Medicine, Izmir, Turkey
| | - Halil Ates
- Department of Ophthalmology, Ege University School of Medicine, Izmir, Turkey
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Salmaninejad A, Gowhari A, Hosseini S, Aslani S, Yousefi M, Bahrami T, Ebrahimi M, Nesaei A, Zal M. Genetics and immunodysfunction underlying Behçet's disease and immunomodulant treatment approaches. J Immunotoxicol 2018; 14:137-151. [PMID: 28693405 DOI: 10.1080/1547691x.2017.1346008] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD.
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Affiliation(s)
- Arash Salmaninejad
- a Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.,b Medical Genetics Research Center, Student Research Committee, Department of Medical Genetics, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran.,c Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Arezoo Gowhari
- d Department of Immunology, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran
| | - Seyedmojtaba Hosseini
- b Medical Genetics Research Center, Student Research Committee, Department of Medical Genetics, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran
| | - Saeed Aslani
- c Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Meysam Yousefi
- b Medical Genetics Research Center, Student Research Committee, Department of Medical Genetics, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran
| | - Tayyeb Bahrami
- e Genetics Research Center , University of Social Welfare and Rehabilitation Sciences , Tehran , Iran
| | - Masoume Ebrahimi
- f Department of Biology, Faculty of Sciences , University of Guilan , Rasht , Iran
| | - Abolfazl Nesaei
- g Department of Basic Sciences , Gonabad University of Medical Sciences , Gonabad , Iran
| | - Masoud Zal
- h Department of Medical Genetics , Shahid Beheshti University of Medical Sciences , Tehran , Iran
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Kacem O, Kaabachi W, Dhifallah IB, Hamzaoui A, Hamzaoui K. Elevated expression of TSLP and IL-33 in Behçet's disease skin lesions: IL-37 alleviate inflammatory effect of TSLP. Clin Immunol 2018; 192:14-19. [PMID: 29631029 DOI: 10.1016/j.clim.2018.03.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 03/25/2018] [Accepted: 03/27/2018] [Indexed: 01/14/2023]
Abstract
The release of TSLP and IL-33 affect the skin integrity, which unsettled transcription factor regulators. We investigate TSLP and IL-33 in Behçet disease (BD) and we prove the effect of the anti-inflammatory cytokine IL-37 in BD skin lesions on TSLP production. TSLP, IL-33 and GATA-3/T-bet, were measured using PCR in BD skin lesions. We tested the suppressive effect of IL-37 on skin samples stimulated with a cytokine mixture inducing TSLP expression. TSLP and IL-33 were increased in BD patients particularly in patients having skin manifestations and correlate with indexed skin lesions. TSLP expression in BD with skin lesions correlates significantly with the transcription factors GATA3/Tbet ratio. The anti-inflammatory mediator IL-37 acted as a suppressor of TSLP-skin synthesis. The microenvironment in cutaneous lesions of BD patients' skin lesions is dominated by the expression of IL-33 and TSLP along an inflammatory Th2-type current. IL-37 acts as a booster to restore homeostasis.
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Affiliation(s)
- Olfa Kacem
- Université de Tunis El Manar, Faculty of Medicine of Tunis, Tunisia; Unit Research "12SP15": "Homeostasis and Cell Dysfuncyion", Tunisia
| | - Wajih Kaabachi
- Unit Research "12SP15": "Homeostasis and Cell Dysfuncyion", Tunisia
| | | | - Agnes Hamzaoui
- Université de Tunis El Manar, Faculty of Medicine of Tunis, Tunisia; Unit Research "12SP15": "Homeostasis and Cell Dysfuncyion", Tunisia; Division of Pulmonology, Department of Paediatric and Respiratory Diseases, Abderrahmane Mami Hospital, Ariana, Tunisia
| | - Kamel Hamzaoui
- Université de Tunis El Manar, Faculty of Medicine of Tunis, Tunisia; Unit Research "12SP15": "Homeostasis and Cell Dysfuncyion", Tunisia.
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Association of MICA Alleles and Human Leukocyte Antigen B in Turkish Patients Diagnosed With Behçet's Disease. Arch Rheumatol 2018; 33:352-357. [PMID: 30632534 DOI: 10.5606/archrheumatol.2018.6704] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 12/25/2017] [Indexed: 12/14/2022] Open
Abstract
Objectives This study aims to investigate whether or not MHC class I polypeptide-related sequence A (MICA) polymorphisms are associated with the susceptibility to Behçet's disease (BD) in a Turkish population. Patients and methods The study included 38 Turkish BD patients (20 males, 18 females; mean age 34±10.9 years) and 51 ethnically matched healthy controls (30 males, 21 females; mean age 36±12.8 years). MICA and human leukocyte antigen B (HLA-B) alleles were determined in all subjects by using the Luminex technology. LABType sequence-specific oligonucleotide MICA test (One Lambda) and sequence-specific oligonucleotide B locus tests (Gene-Probe) were used for the typing studies. Results A total of 16 MICA alleles were found in BD patients as well as in control subjects. The gene frequency of MICA*006 was significantly higher in the BD patients compared to controls (14.5% vs. 0.9%; odds ratio [OR]: 17.092 95% confidence interval [CI] [2.155~135.554]; p<0.05). When haplotypes were evaluated, an association was found between the haplotypes HLA-B*51-MICA*006 (11.8% and 0.9%; OR: 13.567 95% CI [1.679~109.577]; p<0.001) and HLA-B*51-MICA*009 (27.6% and 13.7%; OR: 2.4 95% CI [1.127~5.109]; p<0.05). Frequencies of HLA-B*49-MICA*004 (0% and 6.8%) and HLA-B*52- MICA*009 (0% and 10.7%) were significantly higher in controls compared to BD patients (p<0.05). Conclusion Our study shows that the MICA*006 (MICA-A6) and the MICA*009 alleles are associated with BD susceptibility in HLA-B*51 positive Turkish population, particularly in HLA-B*51 patients with MICA*006, which might be considered as a diagnostic biomarker for BD in the future.
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Atıl A, Deniz A. Could be serum uric acid a risk factor for thrombosis and/or uveitis in Behcet's disease? Vascular 2018; 26:378-386. [PMID: 29360007 DOI: 10.1177/1708538117742831] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction Serum uric acid level increases in many inflammatory conditions. Uric acid triggers the vascular inflammation and artery damage, which causes to an increased risk of endothelial dysfunction and atherosclerosis. It is not clear in the literature whether uric acid contributes to uveitis by similar mechanisms. We investigated whether uric acid level increases in Behcet's disease patients with thrombosis or anterior uveitis. Patients and methods We reviewed the medical records of 914 Behcet's disease. After screening for exclusion criteria, there were 50 Behcet's disease patients with thrombotic complication and as the control group 202 BD patients without any vascular complication were included to the study. In the Anterior uveitis group, there were 53 Behcet's disease patients. The Control group consisted of 39 Behçet's disease patients without eye findings. Results Mean uric acid value was 4.96 ± 1.06 mg/dl in Behcet's disease patients with thrombosis whereas 4.08 ± 0.94 mg/dl in controls, indicating a significant difference ( p < 0.001). There was no significant difference between the mean ages of the patients in both groups. The mean age of the BD group without eye findings was 39.31 ± 10.47 years and that of the Behcet's disease with Anterior Uveitis group was 37.72 ± 9.65 years ( p = 0.453). The mean serum UA in the BD group without eye findings was 4.21 ± 1.21 mg/dl, while in the BD with Anterior Uveitis group it was 4.57 ± 1.37 mg/dl ( p = 0.201). Conclusion The extent of increase in uric acid level was greater in Behcet's disease patients that have a thrombotic complication compared to those without thrombotic complication. Uric acid seems to play a role in the pathogenesis of thrombosis. It is concluded that the elevation of serum uric acid level in patients with anterior uveitis with Behcet's disease is not statistically significant.
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Affiliation(s)
- Avcı Atıl
- 1 Department of Dermatology and Venereology, Kayseri Education and Research Hospital, Kayseri, Turkey
| | - Avcı Deniz
- 2 Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
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Avci A, Avci D, Erden F, Ragip E, Cetinkaya A, Ozyurt K, Atasoy M. Can we use the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume values for the diagnosis of anterior uveitis in patients with Behcet's disease? Ther Clin Risk Manag 2017; 13:881-886. [PMID: 28769565 PMCID: PMC5529084 DOI: 10.2147/tcrm.s135260] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Introduction The purpose of this study was to compare the value of hematological parameters, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV), as indicators of anterior uveal segment involvement in patients with Behcet’s disease (BD). Patients and methods Hospital-based records of a total of 912 patients with BD from the dermatology clinic and healthy volunteers from the checkup clinic were assessed retrospectively. After applying the exclusion criteria of the study, 71 of the BD patients with anterior uveitis, 69 of the BD patients without ophthalmological pathology and 151 healthy volunteers were included in the study. MPV, PLR, and NLR values of patients and healthy volunteers were compared. Results All MPV, PLR, and NLR values of patients who had anterior uveitis were significantly higher than those of other patients and healthy volunteers. Statistically, considering area under curves (ratio): NLR was 0.725 (0.653–0.797), P<0.001; PLR was 0.600 (0.523–0.676), P=0.012, and MPV was 0.358 (0.279–0.437), P<0.001. Conclusion MPV, PLR, and NLR are all valuable for assessment of anterior uveal segment involvement in patients with BD. However, the NLR seems to be better than the PLR and MPV for indicating anterior uveitis due to BD.
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Affiliation(s)
- Atil Avci
- Department of Dermatology and Venereology, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Deniz Avci
- Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Fatma Erden
- Department of Dermatology and Venereology, Cubuk State Hospital, Ankara, Turkey
| | - Ertas Ragip
- Department of Dermatology and Venereology, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Ali Cetinkaya
- Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Kemal Ozyurt
- Department of Dermatology and Venereology, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Mustafa Atasoy
- Department of Dermatology and Venereology, Kayseri Training and Research Hospital, Kayseri, Turkey
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Choi B, Sayeed HM, Islam SMS, Sohn S. Role of N-acetyl galactosamine-4-SO 4, a ligand of CD206 in HSV-induced mouse model of Behçet's disease. Eur J Pharmacol 2017; 813:42-49. [PMID: 28709621 DOI: 10.1016/j.ejphar.2017.07.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 07/06/2017] [Accepted: 07/07/2017] [Indexed: 01/22/2023]
Abstract
CD206 is a macrophage mannose receptor involved in variety of autoimmune and inflammatory diseases. This study aimed to identify the pathogenic role of CD206 in a herpes simplex virus (HSV) induced Behçet's disease (BD) mouse model. CD206 positive cells were detected in peripheral blood mononuclear cells and quantified by flow cytometry. Levels of cytokines were measured by ELISA. CD206 was found to be down-regulated both in vitro (10-6M) and in vivo (200μg/mouse) after treatment with N-acetylgalactosamine (GalNAc), a ligand for CD206. The down-regulation of CD206 was correlated with improvement in BD symptoms. Colchicine (2μg/mouse) or pentoxifylline (400μg/mouse) treated mice displayed improvement in BD symptoms with fewer CD206 positive cells. The prevalence of CD206-positive cells differed between ligand-responsive and non-responsive BD mice. Inhibition of CD206 was associated with down-regulated serum level of interleukin-17 in GalNAc-treated BD mice. These results suggest that the expression of CD206 is correlated with HSV-induced BD symptoms in mice, implicating that CD206 might have a pathogenic role in BD.
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Affiliation(s)
- Bunsoon Choi
- Department of Microbiology, Ajou University School of Medicine, Suwon 443-380, Republic of Korea
| | - Hasan M Sayeed
- Department of Biomedical Science, Ajou University School of Medicine, Suwon 443-380, Republic of Korea
| | - S M Shamsul Islam
- Department of Biomedical Science, Ajou University School of Medicine, Suwon 443-380, Republic of Korea
| | - Seonghyang Sohn
- Department of Microbiology, Ajou University School of Medicine, Suwon 443-380, Republic of Korea; Department of Biomedical Science, Ajou University School of Medicine, Suwon 443-380, Republic of Korea.
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Abstract
Behçet disease is currently considered an "autoinflammatory disease" triggered by infection and environmental factors in genetically predisposed individuals. Although the disease is characterized by recurrent oral and genital aphthous ulcers and ocular involvement, it can affect multiple organ systems. Complex aphthosis is characterized by recurrent oral and/or genital aphthous ulcers. It is important to evaluate the patient with complex aphthosis for Behçet disease and related systemic disorders. We discuss the etiopathogenesis, clinical features, diagnostic criteria, and treatment approaches for complex aphthosis and Behçet disease in light of the current literature.
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Affiliation(s)
- Isil Bulur
- Eskişehir Osmangazi University, Faculty of Medicine, Department of Dermatology, Eskisehir, Turkey.
| | - Meltem Onder
- Gazi University Faculty of Medicine, Department of Dermatology Emeritus Prof, Ankara, Turkey; Dermatology and Laser Center, Reduitstrasse 13, Landau, Germany.
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Alipour S, Nouri M, Sakhinia E, Samadi N, Roshanravan N, Ghavami A, Khabbazi A. Epigenetic alterations in chronic disease focusing on Behçet's disease: Review. Biomed Pharmacother 2017; 91:526-533. [PMID: 28482290 DOI: 10.1016/j.biopha.2017.04.106] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Revised: 04/18/2017] [Accepted: 04/23/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE 'Epigenetics' is specified as the inheritable changes in gene expression with no alterations in DNA sequences. Epigenetics is a rapidly overspreading scientific field, and the study of epigenetic regulation in chronic disease is emerging. This study aims to evaluate epigenetic changes including DNA methylation, histone modification, and non-coding RNAs (ncRNAs) in inflammatory disease, with focus on Behçet's disease. In this review, first we describe the history and classification of epigenetic changes, and then the role of epigenetic alterations in chronic diseases is explained. METHODS Systematic search of MEDLINE, Embase, and Cochrane Library was conducted for all comparative studies since 2000 to 2015 with the limitations of the English language. RESULTS For a notable period of time, researchers have mainly focused on the epigenetic pathways that are involved in the modulation of inflammatory and anti-inflammatory genes. Recent studies have proposed a central role for chronic inflammation in the pathogenesis of chronic disease, including Behçet's disease. CONCLUSION Studies have been reported on the epigenetic of BD showed the role of alterations in the methylation level of IRS elements; histone modifications such as H3K4me27 and H3K4me3; up regulation of miR-182 and miR-3591-3p; down regulation of miR-155, miR-638 and miR-4488 in the pathogenesis of the disease.
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Affiliation(s)
- Shahriar Alipour
- Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Iran; Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Iran
| | - Mohammad Nouri
- Dept. of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ebrahim Sakhinia
- Dept. of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nasser Samadi
- Dept. of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Roshanravan
- Nutrition Research Center, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abed Ghavami
- Nutrition Research Center, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Khabbazi
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Iran.
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Abstract
Abstract
Background: Behcet’s disease (BD) is a chronic, inflammatory multisystemic condition of unknown etiology. Although the cause of BD is not clear, it is believed to be the result of an autoimmune process triggered by an infectious or environmental agent (possibly local to a geographic region) in a genetically predisposed individual.
Objective: To detail current knowledge of the role of microorganisms in the pathogenesis of BD and review the infectious etiology of this disease.
Methods: The review based on publication in SCOPUS, Science direct, and PubMed.
Results: A microbial infection has been implicated in the development of the disease to explain the strong inflammatory reactions observed, the activation of monocytes and macrophages, and the induction of proinflammatory cytokines and chemokines detected. Common factors linking some of the possible pathogenetic agents are extrinsically induced tissue stress or heat shock proteins, which react with host tissues and elicit significant T-helper type 1 cell responses.
Conclusion: Based on collected data, we conclude that the microorganisms discussed seem to participate and, at least in part, act as triggers during the course of BD. By clarifying the microbial associations of BD and finding its etiology, particularly the causative antigens leading to BD, it would be easier to suggest more effective treatment and preventive strategies for this disease.
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Affiliation(s)
- Fatemeh Dabbagh
- Department of Pharmaceutical Biotechnology, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran Iran (Islamic Republic of)
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran (Islamic Republic of)
| | - Afshin Borhani Haghighi
- Department of Neurology, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran (Islamic Republic of)
| | - Younes Ghasemi
- Department of Pharmaceutical Biotechnology, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran Iran (Islamic Republic of)
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran (Islamic Republic of)
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Gholijani N, Ataollahi MR, Samiei A, Aflaki E, Shenavandeh S, Kamali-Sarvestani E. An elevated pro-inflammatory cytokines profile in Behcet's disease: A multiplex analysis. Immunol Lett 2016; 186:46-51. [PMID: 27939191 DOI: 10.1016/j.imlet.2016.12.001] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 12/01/2016] [Indexed: 12/31/2022]
Abstract
The serum levels of sixteen cytokines related to innate immunity, Th1, Th2 and Th17 cells in the sera of 44 patients with Behcet's Disease (BD) and 44 healthy controls have been investigated using the cytokine array technique. Among the cytokines related to innate immunity, the levels of IL-1α, IL-1 β, IL-6, IL-12, IL-15 and TNF-α were statistically higher in BD patients than healthy controls. In the case of Th1- and Th17-related cytokines, IL-2, IFN-γ, IL-17 and IL-23 were significantly higher in patients. From Th2-related cytokines, only IL-13 showed statistically higher levels in patients than controls. Among different evaluated cytokines, the differences in IL-1 α, IL-1 β, IL-6 and Ʃinnate-related cytokines were more prominent between cases and controls. In addition, the results showed that Ʃinnate- and ƩTh17-related cytokines are better indicators of cytokines imbalances in BD than each one of the innate- and Th17-related cytokines. Moreover, disease activity score and clinical activity index can also be affected by the levels of pro-inflammatory (IL-6) and anti-inflammatory (IL-4) cytokines. In conclusion, the results revealed that imbalances in the expression of innate immunity- as well as Th1- and Th17-related cytokines may play not only a pivotal role in BD pathogenesis but also can be important in disease severity.
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Affiliation(s)
| | | | - Afshin Samiei
- Autoimmune Diseases Research Center, Shiraz, Iran; Department of Immunology, Shiraz, Iran
| | - Elham Aflaki
- Autoimmune Diseases Research Center, Shiraz, Iran; Department of Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saeedeh Shenavandeh
- Department of Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran
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Diwo E, Gueudry J, Saadoun D, Weschler B, LeHoang P, Bodaghi B. Long-term Efficacy of Interferon in Severe Uveitis Associated with Behçet Disease. Ocul Immunol Inflamm 2016; 25:76-84. [DOI: 10.1080/09273948.2016.1206204] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Eléonore Diwo
- Ophthalmology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Julie Gueudry
- Ophthalmology Department, Charles Nicolle Hospital, Rouen, France
| | - David Saadoun
- Internal Medicine Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Bertrand Weschler
- Internal Medicine Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Phuc LeHoang
- Ophthalmology Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Bahram Bodaghi
- Ophthalmology Department, Pitié-Salpêtrière Hospital, Paris, France
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Takeuchi M, Karasawa Y, Harimoto K, Tanaka A, Shibata M, Sato T, Caspi RR, Ito M. Analysis of Th Cell-related Cytokine Production in Behçet Disease Patients with Uveitis Before and After Infliximab Treatment. Ocul Immunol Inflamm 2016; 25:52-61. [PMID: 27070371 DOI: 10.3109/09273948.2016.1158276] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To examine antigen-stimulated cytokine production by Behçet disease patients (BD) before and after infliximab infusion. METHODS PBMCs were obtained before and after infliximab infusion in BD patients with or without recurrent uveitis during at least 1 year of infliximab therapy, and from healthy subjects. PBMCs were cultured with IRBP, and Th-related cytokines in cultures were measured. RESULTS Levels of IL-4, IL-6, IL-10 IL-17A, IL-17F, IL-31, IFN-γ, and TNFα were higher in BD before infliximab infusion than in healthy subjects, and these levels were the highest in BD with recurrent uveitis. After infliximab infusion, these cytokine levels were reduced to a greater extent in BD without recurrent uveitis than in BD with recurrence. CONCLUSIONS Th-related cytokines produced by IRBP-stimulated PBMCs were elevated in BD, and infliximab infusion suppressed these cytokines to a greater extent in BD without recurrent uveitis than in those with recurrence.
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Affiliation(s)
- Masaru Takeuchi
- a Department of Ophthalmology , National Defense Medical College , Saitama , Japan
| | - Yoko Karasawa
- a Department of Ophthalmology , National Defense Medical College , Saitama , Japan
| | - Kohzou Harimoto
- a Department of Ophthalmology , National Defense Medical College , Saitama , Japan
| | - Atsushi Tanaka
- a Department of Ophthalmology , National Defense Medical College , Saitama , Japan
| | - Masaki Shibata
- a Department of Ophthalmology , National Defense Medical College , Saitama , Japan
| | - Tomohito Sato
- a Department of Ophthalmology , National Defense Medical College , Saitama , Japan
| | - Rachel R Caspi
- c Laboratory of Immunology, National Eye Institute, National Institutes of Health , Bethesda , Maryland , USA
| | - Masataka Ito
- b Department of Developmental Anatomy and Regenerative Biology , National Defense Medical College , Saitama , Japan
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27
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Seo J, Ahn Y, Zheng Z, Kim BO, Choi MJ, Bang D, Kim DY. Clinical significance of serum YKL-40 in Behçet disease. Br J Dermatol 2016; 174:1337-44. [PMID: 26708309 DOI: 10.1111/bjd.14376] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Serum YKL-40 is an inflammatory biomarker of endothelial dysfunction and may play a role in the inflammatory process of Behçet disease (BD). OBJECTIVES Serum YKL-40 levels were evaluated in patients with BD in order to identify associations with other inflammatory cytokines and establish laboratory parameters. Serum YKL-40 levels were also compared with BD clinical features and disease activity. METHODS In total, 112 patients with BD and 45 age- and sex-matched healthy volunteers were included. Disease activity was assessed with BD Current Activity Form score and Electronic Medical Record-based Activity Index (EMRAI) score. RESULTS Serum YKL-40 levels were significantly higher in patients with BD (median 41·88, range 12·52-171·30 ng mL(-1) ) than in healthy volunteers (median 20·92, range 5·01-64·20 ng mL(-1) ; P < 0·01). The cut-off value for YKL-40 (30·005 ng mL(-1) ) was determined from the receiver operating characteristic curve. EMRAI scores and the proportion of patients in the active phase of BD presenting with two or more major criteria were significantly higher in patients with elevated YKL-40 levels (P = 0·04 and P = 0·04, respectively). A statistically significant elevation in YKL-40 levels was observed in patients with active BD compared with patients with inactive BD (P = 0·05). Serum YKL-40 values were positively correlated with interleukin-6 and EMRAI scores (both P = 0·04), indicating that serum YKL-40 levels are increased in patients with BD and positively correlate with disease activity. CONCLUSIONS YKL-40 may play a role in the pathophysiology of BD and provide a useful marker for monitoring patients with BD.
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Affiliation(s)
- J Seo
- Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Y Ahn
- Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Z Zheng
- Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.,Department of Dermatology, Yanbian University Hospital, Yanji, China
| | - B O Kim
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea
| | - M J Choi
- Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - D Bang
- Department of Dermatology, Catholic Kwandong University, International St. Mary's Hospital, Incheon, Korea
| | - D Y Kim
- Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
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ERDEM CEMAL, BOZKURT YASEMIN, ERMAN BURAK, GÜL AHMET, DEMIR ALPER. MATHEMATICAL MODELING OF BEHÇET'S DISEASE: A DYNAMICAL SYSTEMS APPROACH. J BIOL SYST 2015. [DOI: 10.1142/s0218339015500126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Behçet's Disease (BD) is a multi-systemic, auto-inflammatory disorder that is characterized by recurrent episodes of inflammatory manifestations affecting skin, mucosa, eyes, blood vessels, joints and several other organs. BD is classified as a multifactorial disease with an important contribution of genetics. Genetic studies suggest that there is a strong association of BD with a Class I major histocompatibility complex antigen, named HLA-B*51, along with several other weaker associations with genes encoding proteins involved in inflammation. However, pathogenic mechanisms associated with these genetic variations and their interactions with the environment have not been elucidated yet. In this paper, we present a mathematical model for BD based on a dynamical systems perspective that captures especially the relapsing nature of the disease. We propose a disease progression mechanism and construct a model, in the form of coupled ordinary differential equations (ODEs), which reveals the occurrence pattern of the disease in the population. According to our model, the disease has three distinct modes describing different phenotypes of people carrying HLA-B*51 tissue antigen, namely, the Healthy Carrier, the Potential Patient and the Active Patient. We herein present an exemplary mathematical model for BD, for the first time in the literature, that concisely captures the actions of many cell types together with genetic and environmental effects. The proposed model provides insight into this complex inflammatory disease which may lead to identification of new tools for its treatment and prevention.
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Affiliation(s)
- CEMAL ERDEM
- Computational and Quantitative Biology Lab, Koc University, Istanbul, Turkey
| | - YASEMIN BOZKURT
- Computational and Quantitative Biology Lab, Koc University, Istanbul, Turkey
| | - BURAK ERMAN
- Computational and Quantitative Biology Lab, Koc University, Istanbul, Turkey
| | - AHMET GÜL
- Istanbul Faculty of Medicine, Division of Rheumatology, Istanbul University, Istanbul, Turkey
| | - ALPER DEMIR
- Computational and Quantitative Biology Lab, Koc University, Istanbul, Turkey
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Wang C, Ye Z, Kijlstra A, Zhou Y, Yang P. Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells. Clin Exp Immunol 2014; 177:521-30. [PMID: 24749687 DOI: 10.1111/cei.12352] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2014] [Indexed: 12/18/2022] Open
Abstract
Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.
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Affiliation(s)
- C Wang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China
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Park SR, Park KS, Park YJ, Bang D, Lee ES. CD11a, CD11c, and CD18 gene polymorphisms and susceptibility to Behçet's disease in Koreans. ACTA ACUST UNITED AC 2014; 84:398-404. [PMID: 25155097 DOI: 10.1111/tan.12420] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Revised: 05/04/2014] [Accepted: 07/14/2014] [Indexed: 11/29/2022]
Abstract
Lesions of Behçet's disease (BD) show vascular infiltrates of immune cells expressing integrins. β2 integrins (CD11/CD18) play a major role in cell migration to the inflammatory lesion and also induce cytokine production. Thus, genetic polymorphisms of CD11/CD18 may be associated with the pathogenesis of BD. In this study, nine single nucleotide polymorphisms (SNPs) of the CD11a, CD11c, and CD18 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype analysis in 305 BD patients and 266 healthy controls. The frequencies of genotype rs11574944 CC and haplotype rs11574944C-rs2230433G-rs8058823A in CD11a were significantly lower in BD patients. The frequencies of genotype rs2230429 CC, rs2929 GG, and haplotype rs2230429C-rs2929G in CD11c were higher in BD patients. The frequencies of genotype rs235326CC and haplotype rs2070946A-rs235326C-rs760456G-rs684G in CD18 were significantly higher in the BD patients than in the controls. Other SNPs in CD11a, CD11c, and CD18 gene were not significantly different. Therefore, the major genotype and haplotype of CD11a/CD18 may play a role in decreasing the susceptibility of BD, whereas the major genotype and haplotype of CD11c/CD18 may play a role in increasing the susceptibility of BD.
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Affiliation(s)
- S R Park
- School of Biological Science and Chemistry, Sungshin Women's University, Seoul, Korea
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Immunopathogenesis of ocular Behçet's disease. J Immunol Res 2014; 2014:653539. [PMID: 25061613 PMCID: PMC4100451 DOI: 10.1155/2014/653539] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Accepted: 06/10/2014] [Indexed: 12/12/2022] Open
Abstract
Behçet's disease (BD) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. The ocular involvement of BD, or Behçet's uveitis (BU), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is unclear, researches have revealed that immunological aberrations may be the cornerstone of BD development. General hypothesis of BD pathogenesis is that inflammatory response is initiated by infectious agents or autoantigens in patients with predisposing genetic factors and perpetuated by both innate and acquired immunity. In addition, a network of immune mediators plays a substantial role in the inflammatory cascade. Recently, we found that the immunopathogenesis of BU is distinct from other autoimmune uveitides regarding intraocular effector cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine environment. In addition, accumulating evidence indicates the involvement of Th17 cells in BD and BU. Recent studies on genetics and biologics therapies in refractory BU also support the immunological association with the pathogenesis of BU. In this review, we provide an overview of novel findings regarding the immunopathogenesis of BU.
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Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2014; 1843:2563-2582. [PMID: 24892271 DOI: 10.1016/j.bbamcr.2014.05.014] [Citation(s) in RCA: 1413] [Impact Index Per Article: 128.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 05/22/2014] [Accepted: 05/23/2014] [Indexed: 12/14/2022]
Abstract
Inflammation occurs as a result of exposure of tissues and organs to harmful stimuli such as microbial pathogens, irritants, or toxic cellular components. The primary physical manifestations of inflammation are redness, swelling, heat, pain, and loss of function to the affected area. These processes involve the major cells of the immune system, including monocytes, macrophages, neutrophils, basophils, dendritic cells, mast cells, T-cells, and B-cells. However, examination of a range of inflammatory lesions demonstrates the presence of specific leukocytes in any given lesion. That is, the inflammatory process is regulated in such a way as to ensure that the appropriate leukocytes are recruited. These events are in turn controlled by a host of extracellular molecular regulators, including members of the cytokine and chemokine families that mediate both immune cell recruitment and complex intracellular signalling control mechanisms that characterise inflammation. This review will focus on the role of the main cytokines, chemokines, and their receptors in the pathophysiology of auto-inflammatory disorders, pro-inflammatory disorders, and neurological disorders involving inflammation.
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Affiliation(s)
- Mark D Turner
- Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton, Nottingham NG11 8NS, United Kingdom.
| | - Belinda Nedjai
- Leukocyte Biology Section, National Heart and Lung Institute, Imperial College, South Kensington, London SW7 2AZ, United Kingdom
| | - Tara Hurst
- Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton, Nottingham NG11 8NS, United Kingdom
| | - Daniel J Pennington
- Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, Whitechapel, London E1 2AT, United Kingdom
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Emmi G, Silvestri E, Squatrito D, D'Elios MM, Ciucciarelli L, Prisco D, Emmi L. Behçet's syndrome pathophysiology and potential therapeutic targets. Intern Emerg Med 2014; 9:257-65. [PMID: 24415351 DOI: 10.1007/s11739-013-1036-5] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2013] [Accepted: 12/13/2013] [Indexed: 12/14/2022]
Abstract
Behçet syndrome is a systemic inflammatory disorder characterized by multiorgan involvement such as oral and genital ulcers, uveitis, skin lesions as well as by less frequent, but often more severe, central nervous system and vascular manifestations. The pathogenetic mechanisms are still incompletely known; however the interaction between a specific genetic background and environmental or infectious factors certainly contributes to the immune dysregulation that characterizes this disease. The discovery of new immunological pathways in Behçet syndrome pathogenesis may help us to set up new treatments. In this review, we will focus our attention on the possible mechanisms underlying Behçet syndrome pathogenesis and their potential role as novel therapeutic targets.
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Affiliation(s)
- Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence, L.go G. Brambilla 3, 50134, Florence, Italy,
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Sakly K, Lahmar R, Nefzi F, Hammami S, Harzallah O, Sakly N, Sakly W, Hassine M, Mahjoub S, Ghedira I, Feki S. Phenotypic abnormalities of peripheral blood mononuclear cells in patients with Behçet's disease and association with HLA-B51 expression. Immunol Invest 2014; 43:463-78. [PMID: 24661088 DOI: 10.3109/08820139.2014.886260] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The aim of this study was to investigate the subclasses and the immunophenotypic profile of peripheral mononuclear cells in patients with Behçet's disease (BD) and to assess associations between the expression of HLA-B51 antigen and that of other cell markers. Thirty healthy volunteer blood donors and forty patients with BD were enrolled into this study. Phenotyping was performed using two color flow cytometry. HLA-B51 typing was performed using the complement dependent microlymphocytotoxicity assay. Unlike controls, patients with BD presented a modified immunophenotypic profile of lymphocytes. Compared to those in the remission phase, patients with active BD showed an increased mean of MFI ratio of CD56 on CD16+CD56+ cells (32.47 ± 14.26 versus 23.87 ± 10.3; p = 0.032), increased absolute numbers of CD4(-)CD8(bright) and CD4(+)CD8(+) cells (657.1 ± 463.6 cells/µL versus 319.24 ± 116.4 cells/µL; p = 0.017 and 40.77 ± 36.41 cells/µL versus 10.77 ± 9.78 cells/µL; p < 0.0001, respectively) and an elevated mean of MFI ratio of CD19 on B cells (252.3 ± 56.7 versus 205.67 ± 32.3; p = 0.021). However, expression of HLA-B51 was not associated with any specific immunophenotypic profile. In conclusion, abnormal immunophenotypic profile of peripheral lymphocytes was found in patients with BD, especially in active phase, reflecting an immune dysregulation. Moreover, HLA-B51 expression was not found to be related to the expression of other cell markers.
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Affiliation(s)
- K Sakly
- Research Unit 03/UR/07 "Autoimmunity and Allergy", Faculty of Pharmacy, University of Monastir , Monastir , Tunisia
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Magen E, Delgado JS. Helicobacter pylori and skin autoimmune diseases. World J Gastroenterol 2014; 20:1510-1516. [PMID: 24587626 PMCID: PMC3925859 DOI: 10.3748/wjg.v20.i6.1510] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2013] [Revised: 11/04/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behçet’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review.
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Hamzaoui K, Hamzaoui A. Immunological responses in patients with Behçet’s disease: advances in understanding. EXPERT REVIEW OF OPHTHALMOLOGY 2014. [DOI: 10.1586/eop.12.30] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Alibaz-Oner F, Karatay E, Akpinar IN, Ergun T, Direskeneli H. Evaluation of asymptomatic venous disease by venous Doppler ultrasonography in patients with Behcet's disease without overt thrombosis. Clin Rheumatol 2013; 33:277-80. [DOI: 10.1007/s10067-013-2382-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 08/19/2013] [Accepted: 08/26/2013] [Indexed: 01/30/2023]
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Hamzaoui K, Berraies A, Kaabachi W, Ammar J, Hamzaoui A. Pulmonary manifestations in Behçet disease: impaired natural killer cells activity. Multidiscip Respir Med 2013; 8:29. [PMID: 23556512 PMCID: PMC3637264 DOI: 10.1186/2049-6958-8-29] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 02/28/2013] [Indexed: 11/24/2022] Open
Abstract
Background Behçet’s disease (BD) is a systemic vasculitis with unknown aetiology, where, besides genetic predisposition, an immune dysregulation involving T and B lymphocytes and hyperactive neutrophils contribute to disease pathogenesis. The aim of this study was to determine the cytotoxicity of natural killer (NK) cells in bronchoalveolar lavage (BAL) from BD patients with pulmonary manifestations. Methods BAL was performed in 27 patients with BD and pulmonary manifestations, 14 patients with Rheumatoid Arthritis (RA) and 23 healthy controls (HC). Related orphan receptor C (RORC) and forkheadbox P3 (FOXP3) mRNA transcript were determined in BAL by reverse transcription–polymerase chain reaction (RT-PCR). NK cells, NK cell cytotoxicity, and lymphokine-activated killer (LAK) activity against K562 cells were measured by flow cytometry. Proportions of NK precursors and expression of genes for IL-2 receptor β (IL-2Rβ; CD122), perforin, and granzyme in NK cells were measured by flow cytometry or RT-PCR. Results The analysis of transcription factors revealed an increase in the RORC/FOXP3 ratio (Th17/Treg cells) in BAL from BD patients. Percentages of NK were significantly lower in BD than in RA patients and healthy controls. Purified NK cells derived from BD patients were found to have lower cytotoxicity and LAK activity than those from controls. This defect of NK cells in BD patients was related to down-regulation of perforin and granzyme expression in NK cells. Conclusion In BD patients, the increased RORC/FOXP3 ratio indicated an inflammatory state of the lung. NK cells were decreased together with an impairment of their activity due to a defective expression of granzyme and perforin. These abnormalities possibly contribute to immune system dysregulation found in BAL of BD patients with pulmonary manifestations.
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Affiliation(s)
- Kamel Hamzaoui
- Department of Basic Sciences, Division of Histology and Immunology, Medicine School of Tunis, Tunis El Manar University, 15 Rue DjebelLakdar, Tunis, 1007, Tunisia.
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Redondo-Pachón MD, Enríquez R, Sirvent AE, Andrada E, Noguera-Pons R, Millán I, Amorós F. Tocilizumab treatment for nephrotic syndrome due to amyloidosis in Behcet's disease. Ren Fail 2013; 35:547-50. [PMID: 23472940 DOI: 10.3109/0886022x.2013.773913] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Renal involvement is an unusual but significant Behcet´s disease (BD) complication and AA amyloidosis appears to be the most common etiology. IL-6 is a pro-inflammatory cytokine with an important role in AA amyloidosis development. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that has emerged as an effective and specific treatment in AA amyloidosis secondary to chronic inflammatory disorders. We report on a patient diagnosed with BD who developed nephrotic syndrome caused by renal AA amyloidosis with an excellent response to TCZ therapy.
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40
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Kiss E, Dohán J, Németh J, Poór G. Behcet’s disease: a hardly diagnosed orphan disorder. Orv Hetil 2013; 154:93-101. [DOI: 10.1556/oh.2013.29528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Behcet’s disease is a multisystem autoimmune disease with variable clinial manifestations. The diagnosis may pose a difficult challenge for the clinician, who has to be familiar with the wide spectrum and combination of the symptoms of Behcet’s disease. It is considered a rare disease in Hungary, and there are only few reports on Behcet’s disease in the Hungarian literature. However, the past history of Hungary, the worldwide growing incidence of the disease, and the authors’ experience raise the possibility that the occurrence of the disease is higher than previously thought. In this review the authors present and discuss literature data on the pathogenesis and pathomechanism, as well as their own experience concerning the symptomatology of Behcet’s disease in order to promote diagnosis and offer adequate therapy for the patients. The authors presume that the importance of the disease is underestimated in Hungary due to a considerable number of unrecognized cases and they propose to establish a national registry for Behcets disease. Orv. Hetil., 2013, 154, 93–101.
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Affiliation(s)
- Emese Kiss
- Országos Reumatológiai és Fizioterápiás Intézet Budapest Frankel Leó út 38–40. 1023
- Semmelweis Egyetem, Általános Orvostudományi Kar III. Belklinika, II. Reumatológiai Tanszéki Csoport (ORFI) Budapest
| | - Judit Dohán
- Semmelweis Egyetem, Általános Orvostudományi Kar Szemészeti Klinika Budapest Tömő u. 25–29. 1083
| | - János Németh
- Semmelweis Egyetem, Általános Orvostudományi Kar Szemészeti Klinika Budapest Tömő u. 25–29. 1083
| | - Gyula Poór
- Országos Reumatológiai és Fizioterápiás Intézet Budapest Frankel Leó út 38–40. 1023
- Semmelweis Egyetem, Általános Orvostudományi Kar III. Belklinika, II. Reumatológiai Tanszéki Csoport (ORFI) Budapest
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Cho S, Kim J, Cho SB, Zheng Z, Choi M, Kim D, Bang D. Immunopathogenic characterization of cutaneous inflammation in Behçet’s disease. J Eur Acad Dermatol Venereol 2012; 28:51-7. [DOI: 10.1111/jdv.12054] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Shimizu J, Izumi T, Suzuki N. Aberrant Activation of Heat Shock Protein 60/65 Reactive T Cells in Patients with Behcet's Disease. Autoimmune Dis 2012; 2012:105205. [PMID: 23082245 PMCID: PMC3467778 DOI: 10.1155/2012/105205] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2012] [Accepted: 08/23/2012] [Indexed: 11/18/2022] Open
Abstract
Behcet's disease (BD) is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. We found that heat shock proteins (HSPs) reactive T cells were prevalent in patients with BD. Here, we summarize current findings on HSP reactive T cells and their contribution to the pathogenesis in patients with BD.
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Affiliation(s)
- Jun Shimizu
- Department of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
| | - Tomoko Izumi
- Department of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
- Department of Medicine, Self-Defense Forces Central Hospital, Tokyo 154-8532, Japan
| | - Noboru Suzuki
- Department of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
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Mumcu G, Cimilli H, Karacayli Ü, Inanc N, Türe-Özdemir F, Eksioglu-Demiralp E, Ergun T, Direskeneli H. Salivary levels of HNP 1-3 are related to oral ulcer activity in Behçet's disease. Int J Dermatol 2012; 52:1198-201. [PMID: 22861387 DOI: 10.1111/j.1365-4632.2012.05504.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Saliva contains antimicrobial peptides derived from oral epithelium as well as neutrophils in the innate immune response. The aim of this study was to examine the association between salivary human neutrophil peptide (HNP) 1-3 levels originating from neutrophils and oral ulcers in patients with Behçet's disease (BD). METHODS Ninety-five patients with BD (F/M: 39/56; mean age: 38.7 ± 11.9 years) and 53 healthy controls (HC; F/M: 23/30; mean age: 35.2 ± 10.1 years) were included in the study. The disease control group (F/M: 20/33; mean age: 33.7 ± 10.7 years) was comprised of patients with oral infection regarding endodontic infection (n = 32) and pericoronitis (n = 21). Salivary HNP 1-3 levels of groups were measured in unstimulated samples by ELISA (Hycult, the Netherlands). RESULTS A statistically significant increase was found in salivary HNP 1-3 levels of patients with BD (2268.28 ± 1216.38 μg/ml) compared with HC (1836.49 ± 857.76 μg/ml), patients with endodontic infection (849.9 ± 376.1 μg/ml), and patients with pericoronitis (824.3 ± 284.02 μg/ml; P = 0.024, 0.000 and 0.000, respectively). The ratio of active oral ulcer (100%, n = 14) was higher in low HNP 1-3 levels (≤ 1000 μg/ml) than the others (66.7%, n = 54) in active patients with BD (P = 0.008). Moreover, salivary HNP 1-3 levels were significantly lower in patients with endodontic infection and patients with pericoronitis compared with those in the HC group and patients with BD (P = 0.000). CONCLUSION A decrease in salivary HNP 1-3 levels might be a biological factor for predisposition to oral ulcers in patients with BD and oral infection in healthy patients.
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Affiliation(s)
- Gonca Mumcu
- From the Department of Health Informatics and Technologies, Faculty of Health Sciences Department of Endodontics, Faculty of Dentistry, Marmara University, Istanbul Department of Oral and Maxillofacial Surgery, Gulhane School of Medicine, Ankara Department of Rheumatology Institute of GastroenterologyDepartments of Haematology-Immunology Dermatology, Faculty of Medicine, Marmara University, Istanbul, Turkey
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Yu M, Shi A, Jin B, Jiang X, Liang H, Ouyang C. Superior vena cava occlusion caused by Behçet disease. J Vasc Surg 2012; 55:1488-91. [DOI: 10.1016/j.jvs.2011.10.035] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Revised: 10/10/2011] [Accepted: 10/12/2011] [Indexed: 11/16/2022]
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Development of Immunopathogenesis Strategies to Treat Behçet's Disease. PATHOLOGY RESEARCH INTERNATIONAL 2012; 2012:261989. [PMID: 22550612 PMCID: PMC3324914 DOI: 10.1155/2012/261989] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Accepted: 01/25/2012] [Indexed: 12/14/2022]
Abstract
Behçet disease is a chronic relapsing vasculitis with unclear etiology and immunopathogenesis. Antigenic stimuli, antigen presenting cells, T cells, monocyte, and neutrophil and endothelial cells are major parts of the pathology of the disease. Understanding of the new pathogenic mechanisms based on molecular structure of the disease helps us in improving the novel therapeutic modalities. These drugs target specific and nonspecific inhibition of the immun system. These therapies include biologic agents, new topical and systemic immunosuppressants, tolerizing agents, and immunoablation. Novel treatment will be promising to treat the especially recalcitrant cases to conventional therapy. In this paper, new aspect of the immunopathogenesis of Behçet's diseases and novel treatment modalities will be discussed.
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Hamzaoui K, Abid H, Berraies A, Ammar J, Hamzaoui A. NOD2 is highly expressed in Behçet disease with pulmonary manifestations. JOURNAL OF INFLAMMATION-LONDON 2012; 9:3. [PMID: 22330585 PMCID: PMC3310749 DOI: 10.1186/1476-9255-9-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Accepted: 02/13/2012] [Indexed: 01/28/2023]
Abstract
Background Excessive Th1 cells and TLRs functions are involved in the pathogenesis of Behcet's disease (BD) in response to bacterial antigens. NOD2, an intracellular pathogen recognition sensor, modulates innate defence to muropeptides derived from various bacterial species. To further define a role for NOD2 in BD, we analysed NOD2 transcriptional responses in BAL-MNC from BD patients with pulmonary manifestations. Methods We analysed NOD1, NOD2, T-bet and TLRs mRNA expression with real-time polymerase chain-reaction in BAL cells obtained from 23 BD patients with pulmonary manifestations and their matched controls. Results We found that NOD2 mRNA expression was highly up-regulated in BAL cells from BD and sarcoidosis patients compared to healthy control group (P = 0.001). In BD patients, significant correlation was found between NOD2 and T-bet mRNA expression (r = 0.602; P = 0.0009). In BAL from BD patients, NOD2 and T-bet mRNA expression were significantly correlated with BAL-lymphocytes (r = 0.485, P = 0.010; r = 0684, P = 0.0001 respectively). NOD2 in BD was also correlated with TLR 2(r = 0.444; P = 0.021) and TLR 4 (r = 0.574; P = 0.001) mRNA expression. Conclusion Our results indicate that BAL-MNC from BD patients expressed NOD2 as a result of lung inflammation. TLRs and NOD2 synergize for the induction of proinflammatory cytokines. BAL inflammatory cells showed an increased Th1 situation as indicated by increased T-bet mRNA expression.
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Affiliation(s)
- Kamel Hamzaoui
- Division of Histology and Immunology, Department of Basic Sciences, Medicine School of Tunis, Tunis El Manar University, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia.
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Ahn JK, Cha HS, Lee J, Jeon CH, Koh EM. Correlation of DEFA1 gene copy number variation with intestinal involvement in Behcet's disease. J Korean Med Sci 2012; 27:107-9. [PMID: 22219625 PMCID: PMC3247767 DOI: 10.3346/jkms.2012.27.1.107] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Accepted: 11/02/2011] [Indexed: 01/15/2023] Open
Abstract
Copy number variation has been associated with various autoimmune diseases. We investigated the copy number (CN) of the DEFA1 gene encoding α-defensin-1 in samples from Korean individuals with Behcet's disease (BD) compared to healthy controls (HC). We recruited 55 BD patients and 35 HC. A duplex Taqman® real-time PCR assay was used to assess CN. Most samples (31.1%) had a CN of 5 with a mean CN of 5.4 ± 0.2. There was no significant difference in the CN of the DEFA1 gene between BD patients and HC. A high DEFA1 gene CN was significantly associated with intestinal involvement in BD patients. Variable DEFA1 gene CNs were observed in both BD patients and HC and a high DEFA1 gene CN may be associated with susceptibility to intestinal involvement in BD.
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Affiliation(s)
- Joong Kyong Ahn
- Department of Internal Medicine, Kangbuk Samsung Hospital, Seoul, Korea
| | - Hoon-Suk Cha
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jaejoon Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hong Jeon
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Eun-Mi Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Potential Infectious Etiology of Behçet's Disease. PATHOLOGY RESEARCH INTERNATIONAL 2011; 2012:595380. [PMID: 22254152 PMCID: PMC3255303 DOI: 10.1155/2012/595380] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 10/24/2011] [Indexed: 12/12/2022]
Abstract
Behçet's disease is a multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. The cause of Behçet's disease remains unknown, but epidemiologic findings suggest that an autoimmune process is triggered by an environmental agent in a genetically predisposed individual. An infectious agent could operate through molecular mimicry, and subsequently the disease could be perpetuated by an abnormal immune response to an autoantigen in the absence of ongoing infection. Potentia bacterial are Saccharomyces cerevisiae, mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphylococcus aureus, and Mycoplasma fermentans, but the most commonly investigated microorganism is Streptococcus sanguinis. The relationship between streptococcal infections and Behçet's disease is suggested by clinical observations that an unhygienic oral condition is frequently noted in the oral cavity of Behçet's disease patients. Several viral agents, including herpes simplex virus-1, hepatitis C virus, parvovirus B19, cytomegalovirus, Epstein-Barr virus and varicella zoster virus, may also have some role.
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Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behçet's disease. Autoimmun Rev 2011; 11:687-98. [PMID: 22197900 DOI: 10.1016/j.autrev.2011.11.026] [Citation(s) in RCA: 199] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2011] [Accepted: 11/27/2011] [Indexed: 01/01/2023]
Abstract
Behçet's disease (BD) is a recurrent systemic inflammatory disorder of unknown origin characterized by oral and genital mucous ulcer, uveitis, and skin lesions. Involvement of large vessels, central nervous system (CNS), gastrointestinal tract and thrombotic events are less frequent but can be life threatening. The aim of this review is to provide new insights into the pathogenesis of BD. Over the past year substantial advances have been done in the understanding of the genetic [1,2] and immunology [3] of BD. BD is at the crossroad between autoimmune and autoinflammatory syndromes. In common with autoimmune diseases BD shares class I MHC association. However, in contrast to autoimmune disorders, BD has clinical features that seem to be mostly autoinflammatory. The pathogenesis of BD is still unknown, but major determinants of the genetic and immune system abnormalities have been reported recently. Triggering infectious factors are supposed to participate in the outbreak of BD in genetically predisposed patients. Two recent large genome-wide association study (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. New insights into the perturbations of T cell homeostasis of BD recently emerged. We have recently demonstrated the promotion of Th17 responses and the suppression of regulatory T cells (Tregs) that were driven by interleukin (IL)-21 production and that correlates with BD activity. Inflammatory cells within BD inflammatory lesions included mostly neutrophils, Th1 and Th17 cells, and cytotoxic CD8+ and γδ T cells. Altogether, the recent progresses in the knowledge of BD pathogenesis pave the way for innovative therapy.
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Affiliation(s)
- Marc Pineton de Chambrun
- Department of Internal Medicine and Laboratory I3 Immunology, Immunopathology, Immunotherapy, UMR CNRS 7211, INSERM U959, Groupe Hospitalier La Pitié-Salpetrière, Université Pierre et Marie Curie, Paris 6, Paris, France
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Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet's disease. Arch Oral Biol 2011; 57:642-6. [PMID: 22153317 DOI: 10.1016/j.archoralbio.2011.11.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2011] [Revised: 09/11/2011] [Accepted: 11/04/2011] [Indexed: 11/20/2022]
Abstract
BACKGROUND Oral ulcer is the cardinal clinical sign and increased neutrophilic activity is a part of the pathogenesis in Behcet's disease (BD). Saliva, as a part of the innate immune response, contains antimicrobial peptides (AMPs) that are derived from both oral epithelial cells and neutrophils. The aim of this study was to investigate the associations between salivary levels of AMPs HNP 1-3, LL-37 and S100 and disease course in patients with Behcet's disease (BD). METHODS Fifty-three patients with BD and 44 healthy controls (HC) were included in the study. Disease severity score reflecting organ involvement was calculated. Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva samples by ELISA. RESULTS Salivary HNP 1-3 and S100 levels in BD patients (2715.2 ± 1333.4 μg/ml and 430.6 ± 203.9 ng/ml) were significantly higher compared to HC (1780.6 ± 933.2 μg/ml and 365.3 ± 84.7 ng/ml) (p = 0.000 and p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC (190.9 ± 189.1 vs 143.1 ± 128.9 ng/ml), no significant difference was observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the severity of BD (mild disease: 1975.1 ± 1174.2 μg/ml and 115.9 ± 109.4 ng/ml vs severe disease: 2955.7 ± 1305.6 μg/ml and 215.3 ± 203.8 ng/ml, p=0.020 and p=0.031, respectively). Salivary LL-37 levels also correlated with the number of monthly oral ulcers (r = 0.5 p = 0.000). CONCLUSION An increase in salivary HNP 1-3 and S100 levels might be associated with enhanced local and systemic innate responses in BD.
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