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Nguyen JT, Jessri M, Costa-da-Silva AC, Sharma R, Mays JW, Treister NS. Oral Chronic Graft-Versus-Host Disease: Pathogenesis, Diagnosis, Current Treatment, and Emerging Therapies. Int J Mol Sci 2024; 25:10411. [PMID: 39408739 PMCID: PMC11476840 DOI: 10.3390/ijms251910411] [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: 08/13/2024] [Revised: 09/16/2024] [Accepted: 09/23/2024] [Indexed: 10/20/2024] Open
Abstract
Chronic graft-versus-host disease (cGvHD) is a multisystem disorder that occurs in recipients of allogeneic hematopoietic (alloHCT) stem cell transplants and is characterized by both inflammatory and fibrotic manifestations. It begins with the recognition of host tissues by the non-self (allogeneic) graft and progresses to tissue inflammation, organ dysfunction and fibrosis throughout the body. Oral cavity manifestations of cGVHD include mucosal features, salivary gland dysfunction and fibrosis. This review synthesizes current knowledge on the pathogenesis, diagnosis and management of oral cGVHD, with a focus on emerging trends and novel therapeutics. Data from various clinical studies and expert consensus are integrated to provide a comprehensive overview.
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Affiliation(s)
- Joe T. Nguyen
- Nguyen Laboratory, Head and Neck Cancer Section, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Oral Immunobiology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; (A.C.C.-d.-S.); (R.S.); (J.W.M.)
| | - Maryam Jessri
- Metro North Hospital and Health Service, Queensland Health, Brisbane, QLD 4029, Australia;
- Department of Oral Medicine and Pathology, School of Dentistry, The University of Queensland, Herston, QLD 4072, Australia
| | - Ana C. Costa-da-Silva
- Oral Immunobiology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; (A.C.C.-d.-S.); (R.S.); (J.W.M.)
| | - Rubina Sharma
- Oral Immunobiology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; (A.C.C.-d.-S.); (R.S.); (J.W.M.)
| | - Jacqueline W. Mays
- Oral Immunobiology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; (A.C.C.-d.-S.); (R.S.); (J.W.M.)
| | - Nathaniel S. Treister
- Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02114, USA
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Tollemar V, Garming Legert K, Sugars RV. Perspectives on oral chronic graft-versus-host disease from immunobiology to morbid diagnoses. Front Immunol 2023; 14:1151493. [PMID: 37449200 PMCID: PMC10338056 DOI: 10.3389/fimmu.2023.1151493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 06/12/2023] [Indexed: 07/18/2023] Open
Abstract
Chronic Graft-versus-Host Disease (cGVHD) is a major long-term complication, associated with morbidity and mortality in patients following allogenic hematopoietic cell transplantation (HCT) for immune hematopoietic disorders. The mouth is one of the most frequently affected organs after HCT (45-83%) and oral cGVHD, which may appear as the first visible sign. Manifestations present with mucosal lichenoid lesions, salivary gland dysfunction and limited oral aperture. Diagnosis of oral cGVHD severity is based on mucosal lesions with symptoms of sensitivity and pain and reduced oral intake. However, diagnostic difficulties arise due to subjective definitions and low specificity to cover the spectrum of oral cGVHD. In recent years there have been significant improvements in our understanding of the underlying oral cGVHD disease mechanisms. Drawing upon the current knowledge on the pathophysiology and biological phases of oral cGVHD, we address oral mucosa lichenoid and Sjogren's Syndrome-like sicca syndromes. We consider the response of alloreactive T-cells and macrophages to recipient tissues to drive the pathophysiological reactions and biological phases of acute inflammation (phase 1), chronic inflammation and dysregulated immunity (phase 2), and subsequent aberrant fibrotic healing (phase 3), which in time may be associated with an increased malignant transformation rate. When formulating treatment strategies, the pathophysiological spectrum of cGVHD is patient dependent and not every patient may progress chronologically through the biological stages. As such there remains a need to address and clarify personalized diagnostics and management to improve treatment descriptions. Within this review, we highlight the current state of the art knowledge on oral cGVHD pathophysiology and biological phases. We address knowledge gaps of oral cGVHD, with a view to facilitate clinical management and improve research quality on lichenoid biology and morbid forms of oral cGVHD.
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Affiliation(s)
| | | | - Rachael V. Sugars
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
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Deng X, Wang Y, Jiang L, Li J, Chen Q. Updates on immunological mechanistic insights and targeting of the oral lichen planus microenvironment. Front Immunol 2023; 13:1023213. [PMID: 36700192 PMCID: PMC9870618 DOI: 10.3389/fimmu.2022.1023213] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 12/19/2022] [Indexed: 01/12/2023] Open
Abstract
Oral lichen planus (OLP) is a chronic immune inflammatory disease that is an oral potentially malignant disorder (OPMD), occurs in the oral mucosa and affects approximately 0.5% to 4% of the general population. There are usually five types of OLP: reticular/papular, plaque-like, atrophic/erythematous, erosive/ulcerative, and bullous. Furthermore, the chance of causing oral squamous cell carcinoma (OSCC) is 1.4%. Although the etiology of OLP is still unknown, accumulating evidence supports that immune dysregulation may play a vital role in the pathogenesis of OLP, especially the massive production of various inflammatory cells and inflammatory mediators. In this review, we focus on the relationship between OLP and its immune microenvironment. We summarize current developments in the immunology of OLP, summarizing functional cell types and crucial cytokines in the OLP immune microenvironment and the underlying mechanisms of key signaling pathways in the OLP immune microenvironment. We highlight the application potential of targeted immune microenvironment therapy for OLP.
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Affiliation(s)
| | | | - Lu Jiang
- *Correspondence: Jing Li, ; Lu Jiang,
| | - Jing Li
- *Correspondence: Jing Li, ; Lu Jiang,
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Langerhans Cells, T Cells, and B Cells in Oral Lichen Planus and Oral Leukoplakia. Int J Dent 2022; 2022:5430309. [PMID: 35360707 PMCID: PMC8964229 DOI: 10.1155/2022/5430309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 03/05/2022] [Indexed: 11/18/2022] Open
Abstract
Although oral lichen planus (OLP) and oral leukoplakia (LPL) have different pathogenetic profiles, both may involve chronic inflammation. The aim of this observational study was to evaluate the inflammatory cell profiles of OLP and LPL. The inflammatory cell infiltrates in patients with OLP and LPL were analyzed for the presence of Langerhans cells (LCs; CD1a), T cells (CD3), and B cells (CD20), as well as for the proliferation marker Ki-67. Biopsied specimens from patients with OLP (N = 14) and LPL without dysplasia (N = 13) were immunohistochemically stained with antibodies directed against CD1a, CD3, CD20, and Ki-67, followed by quantitative analyses. A significant increase in the number of CD3+ cells and CD20+ cells was found in the submucosa of OLP, as compared to LPL (p < 0.01). Likewise, the number of CD3+ cells was significantly higher in the epithelium of OLP than of LPL (p < 0.05). No differences were found in the expression of Ki-67 and the number of CD1a+ cells between the two groups. Although an immune response is elicited in both conditions, there are differences at the cellular level between OLP and LPL. A more robust immune activation involving T cells and B cells is seen in OLP. The role of B cells in OLP needs to be further elucidated. Although the number of B cells in LPL is low, their role in the inflammatory response cannot be ruled out.
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Kumar TA, Veeravarmal V, Nirmal RM, Amsaveni R, Nassar MHM, Kesavan G. Expression of Cluster of Differentiation 1a-Positive Langerhans Cells in Oral Lichen Planus. Indian J Dermatol 2019; 64:41-46. [PMID: 30745634 PMCID: PMC6340233 DOI: 10.4103/ijd.ijd_350_16] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background/Purpose: Lichen planus is a T-cell-mediated mucocutaneous disorder characterized histopathologically by a band of chronic inflammatory cells in the subepithelial zone and degeneration of basal layer. The present study was aimed to evaluate the distribution and quantitative assessment of cluster of differentiation 1a (CD1a)-positive Langerhans cells (LCs) in oral lichen planus (OLP), thus to determine the role of LCs pertaining to the changes occurring in OLP. Materials and Methods: Five cases of normal oral mucosa and 20 cases of OLP were immunostained with CD1a antibody; the positive cells were counted manually in the photomicrographs and statistically analyzed using t-test, Mann–Whitney test, and Wilcoxon signed-rank test. Results: The average percentage of CD1a-positive LCs in normal subjects was 0.9%, and in the OLP cases higher percentage was observed (3.93%). The statistical comparison of these two parameters was significant (P=0.018). The degree of basal cell degeneration and density of subepithelial infiltrate on statistical comparison with the concentration of CD1a-positive LCs showed significant results. Conclusion: LCs play a pivotal role in the recruitment of CD4+ and CD8+ cells to the subepithelial region and basal keratinocytes apoptosis. A small number of study subjects, assessment of only CD1a molecule and LCs in the epidermis only were a few of the drawbacks of the study.
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Affiliation(s)
- Thankanadar Arul Kumar
- Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
| | - Veeran Veeravarmal
- Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
| | - Ramdas Madhavan Nirmal
- Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
| | - Ramamoorthy Amsaveni
- Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
| | - Mohamed Hanifa Mohamed Nassar
- Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
| | - Ganesan Kesavan
- Department of Oral Pathology, Madha Dental College and Hospital, Chennai, Tamil Nadu, India
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Nasiri S, Bidari Zerehpoosh F, Abdollahimajd F, Younespour S, Esmaili Azad M. A comparative immunohistochemical study of epidermal and dermal/perifollicular Langerhans cell concentration in discoid lupus erythematosus and lichen planopilaris: a cross-sectional study. Lupus 2018; 27:2200-2205. [PMID: 30376791 DOI: 10.1177/0961203318808587] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND There are times when differentiation between discoid lupus erythematosus (DLE) and lichen planopilaris (LPP) becomes quite challenging clinicopathologically. OBJECTIVES The aim of this study was to evaluate and compare the concentration, distribution pattern and role of Langerhans cells (LCs), identified by CD1a staining in DLE and LPP. METHODS Twenty-five specimens of skin biopsies from patients diagnosed with LPP and DLE were included. Immunohistochemistry (IHC) staining was performed against CD1a antigen to assess and compare the concentration and distribution pattern of LCs. RESULTS Compared with LPP, the mean number of epidermal CD1a+ cells per three high power fields was significantly lower in DLE ( p = 0.003). On the other hand, DLE cases had a significantly higher mean number of dermal/perifollicular CD1a+ cells in three high power fields than LPP cases ( p = 0.01). LIMITATIONS A small sample size and limited IHC markers. CONCLUSIONS There are differences in the density and distribution pattern of LCs in LPP and DLE in the epidermis and perifollicular regions. Our findings of a statistically significant decrease in LC concentration in the epidermis of DLE cases and also in the perifollicular region of LPP may serve as helpful clues in further characterization of these entities, especially in equivocal cases. However, more extensive studies are required to better understand the underlying immunopathogenesis of these diseases in providing further clues to a specific diagnosis.
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Affiliation(s)
- S Nasiri
- 1 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - F Bidari Zerehpoosh
- 2 Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - F Abdollahimajd
- 1 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - S Younespour
- 3 National Institute for Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - M Esmaili Azad
- 1 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Tollemar V, Tudzarovski N, Boberg E, Törnqvist Andrén A, Al-Adili A, Le Blanc K, Garming Legert K, Bottai M, Warfvinge G, Sugars R. Quantitative chromogenic immunohistochemical image analysis in cellprofiler software. Cytometry A 2018; 93:1051-1059. [DOI: 10.1002/cyto.a.23575] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Revised: 07/14/2018] [Accepted: 07/16/2018] [Indexed: 02/06/2023]
Affiliation(s)
- V. Tollemar
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine; Karolinska Institutet; Huddinge Sweden
| | - N. Tudzarovski
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine; Karolinska Institutet; Huddinge Sweden
| | - E. Boberg
- Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine; Karolinska Institutet; Stockholm Sweden
| | - A. Törnqvist Andrén
- Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine; Karolinska Institutet; Stockholm Sweden
| | - A. Al-Adili
- Department of Oral and Maxillofacial Surgery; Karolinska University Hospital; Stockholm Sweden
| | - K. Le Blanc
- Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine; Karolinska Institutet; Stockholm Sweden
| | - K. Garming Legert
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine; Karolinska Institutet; Huddinge Sweden
| | - M. Bottai
- Unit of Biostatistics, Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - G. Warfvinge
- Department of Oral Pathology, Faculty of Odontology; Malmö University; Malmö Sweden
| | - R.V. Sugars
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine; Karolinska Institutet; Huddinge Sweden
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Marshall A, Celentano A, Cirillo N, Mirams M, McCullough M, Porter S. Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus. J Oral Sci 2018; 59:373-382. [PMID: 28904313 DOI: 10.2334/josnusd.16-0334] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP. In the present study, we used a reverse transcriptase-polymerase chain reaction assay to assess whether CD40-a receptor found mainly on antigen presenting cells-and the costimulatory molecule CD86 were expressed in oral keratinocytes (three strains of primary normal oral keratinocytes and the H357 cell line) in the presence or absence of IFN-γ. To further characterize the involvement of CD40 in OLP, expression and distribution of receptor and ligand (CD40/CD154) in tissues from OLP were evaluated by immunohistochemistry. The present results are the first to show that both CD40 and CD86 are constitutively expressed at low levels in oral keratinocytes and that their expression was enhanced by IFN-γ stimulation. The intensity of CD40 staining in OLP tissues was strong. Taken together, the results strongly suggest that CD40 and CD86 play a role in the pathophysiology of oral inflammatory diseases such as OLP.
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Affiliation(s)
| | - Antonio Celentano
- Department of Neuroscience, Reproductive and Odontostomatological Sciences, University Federico II of Naples.,Melbourne Dental School and Oral Health Cooperative Research Centre, The University of Melbourne
| | - Nicola Cirillo
- Melbourne Dental School and Oral Health Cooperative Research Centre, The University of Melbourne
| | - Michiko Mirams
- Melbourne Dental School and Oral Health Cooperative Research Centre, The University of Melbourne
| | - Michael McCullough
- Melbourne Dental School and Oral Health Cooperative Research Centre, The University of Melbourne
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Kulkarni G, Sakki EP, Kumar YV, Kolimi S, Perika R, Karthik KV, Kumar KM, Kalyan VS. Expression of CD1a by Langerhan's Cells in Oral Lichen Planus - A Retrospective Analysis. J Clin Diagn Res 2016; 10:ZC28-31. [PMID: 27504405 DOI: 10.7860/jcdr/2016/19189.7966] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Accepted: 05/05/2016] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Langerhan's Cells (LCs) are dendritic cells of the oral epithelium which play a role in a series of oral lesions from gingivitis to oral cancer. Oral Lichen Planus (OLP) is an oral mucosal T-lymphocyte mediated immunologic reaction to an unidentified putative antigen or allergen. AIM The aim of this study was to quantify the presence of immature LCs in OLP comparing them with normal epithelium. MATERIALS AND METHODS A retrospective study using 30 of OLP cases were conducted. Immunohistochemistry was performed using polyclonal anti-CD1a antibodies to identify LCs in 10 cases of normal tissue and 30 samples of OLP. The distribution of LCs among lesional tissue and normal mucosa was analysed using Mann-Whitney U test. RESULTS LC population in OLP was significantly higher when compared to the normal epithelium (p<0.001). CONCLUSION The increase in LCs indicates the active role played during the antigen detection in OLP and subsequent presentation to T-lymphocytes.
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Affiliation(s)
- Ganesh Kulkarni
- Senior Lecturer, Department of Oral Pathology, Malla Reddy Institute of Dental Sciences , Hyderabad, Telangana, India
| | - Esther Priyadarshini Sakki
- Senior Lecturer, Department of Oral Pathology, Meghana Institute of Dental sciences , Nizamabad, Telangana, India
| | - Yennavaram Vijay Kumar
- Associate Professor, Department of Public Health Dentistry, MNR Dental College and Hospital , Sangareddy, Telangana, India
| | - Sadananda Kolimi
- Assistant Professor, Department of Periodontics, Government Dental College and Research Institute , VIMS, Bellary, Karnataka, India
| | - Ravi Perika
- Senior Lecturer, Department of Oral Pathology, Malla Reddy Institute of Dental Sciences , Hyderabad, Telangana, India
| | - Kalepu Venkata Karthik
- Senior Lecturer, Department of Oral Pathology, SVS Institute of Dental Sciences , Mahbubnagar, Telangana, India
| | - Kandukuri Mahesh Kumar
- Assistant Professor, Department of Pathology, Malla Reddy Institute of Medical Sciences , Hyderabad, Telangana, India
| | - Venumbaka Siva Kalyan
- Reader, Department of Public Health Dentistry, Mamatha Dental College , Khammam, Telangana, India
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Pérez CA, Rabanales R, Rojas-Alcayaga G, Larrondo M, Escobar AF, López MN, Salazar-Onfray F, Alfaro JI, González FE. Dendritic cell chimerism in oral mucosa of transplanted patients affected by graft-versus-host disease. J Oral Pathol Med 2015; 45:127-35. [PMID: 26102283 DOI: 10.1111/jop.12338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2015] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Graft-versus-host disease (GVHD) is one of the main complications after haematopoietic stem cell transplantation. Clinical features of GVHD include either an acute (aGVHD) or a chronic (cGVHD) condition that affects locations such as the oral mucosa. While the involvement of the host's dendritic cells (DCs) has been demonstrated in aGVHD, the origin (donor/host) and mechanisms underlying oral cGVHD have not been completely elucidated. In this study, we intend to determine the origin of DCs present in mucosal tissue biopsies from the oral cavity of transplanted patients affected by cGVHD. METHODS We purified DCs, from oral biopsies of three patients with cGVHD, through immunobeads and subsequently performed DNA extraction. The origin of the obtained DCs was determined by PCR amplification of 13 informative short tandem repeat (STR) alleles. We also characterised the DCs phenotype and the inflammatory infiltrate from biopsies of two patients by immunohistochemistry. RESULTS Clinical and histological features of the biopsies were concordant with oral cGVHD. We identified CD11c-, CD207- and CD1a-positive cells in the epithelium and beneath the basal layer. Purification of DCs from the mucosa of patients affected by post-transplantation cGVHD was >95%. PCR-STR data analysis of DCs DNA showed that 100% of analysed cells were of donor origin in all of the evaluated patients. CONCLUSION Our results demonstrate that resident DCs isolated from the oral tissue of allotransplanted patients affected by cGVHD are originated from the donor. Further research will clarify the role of DCs in the development and/or severity of oral cGVHD.
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Affiliation(s)
- Claudio A Pérez
- Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, Santiago, Chile
| | - Ramón Rabanales
- Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, Santiago, Chile
| | - Gonzalo Rojas-Alcayaga
- Department of Oral Pathology and Medicine, Faculty of Dentistry, University of Chile, Santiago, Chile
| | - Milton Larrondo
- Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, Santiago, Chile
| | - Alejandro F Escobar
- Research Institute of Dental Sciences, Faculty of Dentistry, University of Chile, Santiago, Chile
| | - Mercedes N López
- Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, Santiago, Chile.,Disciplinary Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.,Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile
| | - Flavio Salazar-Onfray
- Disciplinary Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.,Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile
| | - Jorge I Alfaro
- Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, Santiago, Chile
| | - Fermín E González
- Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.,Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile
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Grossmann SDMC, Oliveira CDNAD, Souto GR, Góes C, Mesquita RA. Oral lichenoid lesion: A review of the literature. World J Stomatol 2015; 4:103. [DOI: 10.5321/wjs.v4.i2.103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 01/26/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
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Abstract
Oral lichen planus (OLP) is commonly found in middle-aged women. Although the cause is unknown, research points to several complex immunologic events and cells that are responsible for the inflammatory destruction and chronicity of these lesions. Biopsy for histologic diagnosis is recommended. The mainstay of treatment remains topical corticosteroids; however, newer therapies such as immunomodulating agents are available for recalcitrant lesions. In cases of lichenoid mucositis or reactions, treatment should be directed at identifying and removing the presumed cause. Given the apparent risk of squamous cell carcinoma in these patients, frequent follow-up and repeat biopsy are vital.
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Affiliation(s)
- Scott S De Rossi
- Department of Oral Health and Diagnostic Sciences, College of Dental Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA; Department of Otolaryngology/Head & Neck Surgery, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA; Department of Dermatology, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
| | - Katharine Ciarrocca
- Department of Oral Rehabilitation, College of Dental Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA
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13
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Gale G, Ostman S, Saalman R, Telemo E, Jontell M, Hasséus B. Immunophenotype in orofacial granulomatosis with and without Crohn's disease. Med Oral Patol Oral Cir Bucal 2014; 19:e584-591. [PMID: 25350593 PMCID: PMC4259375 DOI: 10.4317/medoral.20187] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Accepted: 08/22/2014] [Indexed: 01/29/2023] Open
Abstract
Objectives: The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn’s disease (OFG+CD).
Study Design: Biopsy specimens with granulomas were obtained from patients with OFG-S (n=11) and OFG+CD (n=11) and immunostained with antibodies against CD1a, CD3, CD4, CD8, CD11c, CD20, CD68 and mast cell tryptase, followed by quantitative analysis.
Results: Analyses of the connective tissue revealed a significantly higher number of CD3-expressing T cells and CD11c-expressing dendritic cells in the connective tissue of patients with OFG-S compared to patients with OFG+CD. Mast cells displayed a high level of activation, although no significant difference was detected when comparing the two groups.
Conclusions: The results show a different composition of the inflammatory infiltrate in patients with OFG-S compared to patients with OFG+CD. The present observations support that partly divergent immune mechanisms are involved in these two different subcategories of OFG.
Key words:Granulomas, autoimmunity, T cells, B cells, dendritic cells, children, adults.
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Affiliation(s)
- Gita Gale
- Department of Oral Medicine and Pathology, Institute of Odontology The Sahlgrenska Academy, University of Gothenburg, Box 450, SE405 30 Gothenburg, Sweden,
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15
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Lu R, Zhang J, Sun W, Du G, Zhou G. Inflammation-related cytokines in oral lichen planus: an overview. J Oral Pathol Med 2013; 44:1-14. [PMID: 24329772 DOI: 10.1111/jop.12142] [Citation(s) in RCA: 128] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2013] [Indexed: 12/11/2022]
Abstract
Cytokines are powerful mediators which play a central role in both innate and adapted immune responses. Aberrant productions of cytokines may lead to the onset of immune deficiency, allergy or autoimmunity, which are involved in the mechanisms of various immune-mediated inflammatory diseases. Oral lichen planus (OLP) is a chronic inflammation disease affecting the oral mucosa with unknown aetiology. Previous studies have described the abnormal expression patterns of various inflammation-related cytokines, such as IL-1, 2, 4, 5, 6, 8, 10, 12, 17, 18, TGF-β, IFN-γ and TNF-α, in lesions, saliva, serum and peripheral blood mononuclear cells from patients with OLP, which may reflect the immune dysregulation status and emerge as central players in the immunopathogenesis of OLP. Besides, the gene polymorphisms of several cytokines such as IFN-γ, TNF-α, IL-4, IL-10 have been found to be involved in the susceptibility of OLP. In this review, we gave a brief introduction of the characteristics and biological functions of these inflammation-related cytokines and summarized for the first time the current knowledge on the involvement of inflammation-related cytokines in OLP. Further research on the exact roles of these cytokines will aid the understanding of the pathogenesis and the identification of novel therapeutic approaches of OLP.
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Affiliation(s)
- Rui Lu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, PR China; Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, China
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Payeras MR, Cherubini K, Figueiredo MA, Salum FG. Oral lichen planus: focus on etiopathogenesis. Arch Oral Biol 2013; 58:1057-69. [PMID: 23660124 DOI: 10.1016/j.archoralbio.2013.04.004] [Citation(s) in RCA: 156] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 03/09/2013] [Accepted: 04/11/2013] [Indexed: 02/07/2023]
Abstract
Lichen planus is a chronic mucocutaneous inflammatory disease, which frequently affects the oral mucosa of white females over 40 years old. Its aetiology remains uncertain and the pathogenesis is still the object of much speculation. The present paper presents the most well known antigens, and describes the action of different cells and proteins associated with the development of that disease, as well as the possible agents involved with its malignant transformation. Different external agents, especially virus, and internal agents, like stress, and the heat shock protein antigen expression, associated or not, can alter the basal keratinocytes of the oral mucosa making them susceptible to apoptosis by CD8(+) cytotoxic T cell as well as activate matrix metalloproteinase and mast cell degranulation, which produce a great range of inflammatory mediators and cytokines determining the clinical onset of the disease. Regarding carcinogenesis, since it is a complex process and presents multifactorial origin, it is believed that there may be a synergism between intrinsic, such as inflammation mediators, and extrinsic agents (tobacco, alcohol, viral infections) for the OLP malignant transformation to occur. However, further studies are needed to better understand the origin, pathogenesis and process of malignant transformation of OLP.
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Affiliation(s)
- Márcia Rodrigues Payeras
- Oral Medicine Division, Pontifical Catholic University of Rio Grande do Sol, Av. Ipiranga 6690, Porto Alegre, RS, Brazil.
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17
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Simark-Mattsson C, Eklund C. Reduced immune responses to purified protein derivative and Candida albicans in oral lichen planus. J Oral Pathol Med 2013; 42:691-7. [PMID: 23607487 DOI: 10.1111/jop.12069] [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] [Accepted: 03/22/2013] [Indexed: 12/31/2022]
Abstract
BACKGROUND Impairment of cellular immunity is reported in lichen planus, an autoimmune disease affecting mucosae and skin. Our aim was to investigate immune responses directed against a set of microbial antigens in patients with oral lichen planus and in matched controls. METHODS Venous blood was obtained, and the mononuclear cells were enriched by density gradient centrifugation. The proliferation of peripheral blood mononuclear cells was assessed, following stimulation with purified protein derivative (PPD), Candida albicans, phytohemagglutinin or when cells were left unstimulated, after three or six days of cell culture. The production of interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), G-CSF, GM-CSF, MCP-1, MIP-ß was assessed in supernatants using the Bio-plex(®) assay and was complemented with ELISA for selected cytokines. RESULTS Patients with oral lichen planus demonstrated reduced proliferative responses against PPD (P < 0.05) and C. albicans (P < 0.05). The majority of investigated cytokines, including the pro-inflammatory, IFN-γ and TNF-α were expressed at reduced levels in PPD-stimulated supernatants from patients with oral lichen planus. CONCLUSIONS Collectively, the findings suggested that memory lymphocytes from patients with oral lichen planus (OLP) may have an impaired functional ability to react against certain recall antigens, as part of a generalized response, which may reflect immune regulatory processes. Further studies are needed to clarify the mechanisms of down-regulation in OLP pathogenesis and progression.
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Affiliation(s)
- Charlotte Simark-Mattsson
- Department of Cariology, Institute of Odontology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Public Dental Health Service Västra Götaland, University Clinics, Gothenburg, Sweden
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18
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19
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Mattila R, Rautava J, Syrjänen S. Human papillomavirus in oral atrophic lichen planus lesions. Oral Oncol 2012; 48:980-984. [DOI: 10.1016/j.oraloncology.2012.04.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Revised: 04/05/2012] [Accepted: 04/23/2012] [Indexed: 01/18/2023]
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Öhman J, Magnusson B, Telemo E, Jontell M, Hasséus B. Langerhans cells and T cells sense cell dysplasia in oral leukoplakias and oral squamous cell carcinomas--evidence for immunosurveillance. Scand J Immunol 2012; 76:39-48. [PMID: 22469080 DOI: 10.1111/j.1365-3083.2012.02701.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Leukoplakias (LPLs) are lesions in the oral mucosa that may develop into oral squamous cell carcinoma (OSCC). The objective of this study was to assess presence and distribution of dendritic Langerhans cells (LCs) and T cells in patients with LPLs with or without cell dysplasia and in oral squamous cell carcinoma (OSCC). Biopsy specimens from patients with leukoplakias (LPLs) with or without dysplasia and oral squamous cell carcinoma (OSCC) were immunostained with antibodies against CD1a, Langerin, CD3, CD4, CD8 and Ki67, followed by quantitative analysis. Analyses of epithelium and connective tissue revealed a significantly higher number of CD1a + LCs in LPLs with dysplasia compared with LPLs without dysplasia. Presence of Langerin + LCs in epithelium did not differ significantly between LPLs either with or without dysplasia and OSCC. T cells were found in significantly increased numbers in LPLs with dysplasia and OSCC. The number of CD4+ cells did not differ significantly between LPLs with and without dysplasia, but a significant increase was detected when comparing LPLs with dysplasia with OSCC. CD8+ cells were significantly more abundant in OSCC and LPLs with dysplasia compared with LPLs without dysplasia. Proliferating cells (Ki67+) were significantly more abundant in OSCC compared to LPLs with dysplasia. Confocal laser scanning microscopy revealed colocalization of LCs and T cells in LPLs with dysplasia and in OSCC. LCs and T cells are more numerous in tissue compartments with dysplastic epithelial cells and dramatically increase in OSCC. This indicates an ongoing immune response against cells with dysplasia.
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Affiliation(s)
- J Öhman
- Department of Oral Medicine and Pathology, Institute of Odontology, Gothenburg, Sweden.
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Hymes SR, Alousi AM, Cowen EW. Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host disease. J Am Acad Dermatol 2012; 66:515.e1-18; quiz 533-4. [PMID: 22421123 DOI: 10.1016/j.jaad.2011.11.960] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2011] [Revised: 11/09/2011] [Accepted: 11/12/2011] [Indexed: 01/04/2023]
Abstract
Approximately 25,000 allogeneic hematopoietic cell transplants are performed worldwide each year for a variety of malignant and non-malignant conditions. Graft-versus-host disease represents one of the most frequent complications and is a major source of long-term morbidity and mortality. Whereas acute graft-versus-host disease is induced by recognition of host tissues as foreign by immunocompetent donor cells, the pathogenesis of chronic graft-versus-host disease is not as well understood, and continues to be a major treatment challenge. Part I of this two-part series reviews the epidemiologic factors, classification, pathogenesis, and clinical manifestations of acute and chronic graft-versus-host disease. Part II discusses the topical, physical, and systemic treatment options available to patients with graft-versus-host disease.
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Affiliation(s)
- Sharon R Hymes
- Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
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22
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Pimentel VN, de Matos LS, Soares TCB, Adam R, Metze K, Correa MEP, de Souza CA, Cintra ML. Perforin and granzyme B involvement in oral lesions of lichen planus and chronic GVHD. J Oral Pathol Med 2011; 39:741-6. [PMID: 20618609 DOI: 10.1111/j.1600-0714.2010.00917.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Oral lesions of lichen planus and chronic graft-vs.-host disease (cGVHD) have similar clinical and histological features, but distinct etiology. Apoptosis induced by cytotoxic T lymphocyte has been proposed as a mechanism of keratinocytes death. Cytotoxicity can be mediated by granules containing granzyme B and perforin. Since common features can reflect similarities in immunological mechanisms, we studied the role of those molecules in both diseases. METHODS We analyzed 29 cases of oral lichen planus and 27 of oral cGVHD. The sections were studied on H&E, perforin and granzyme B staining. RESULTS The total means (epithelium plus connective tissue number) of the granzyme B- and perforin-positive cells were significantly higher in cGVHD than in oral lichen planus lesions (P<0.05). Also, it was found that the higher the number of perforin+ cells, the higher the number of granzyme-B+ cells in the epithelium and in the connective tissue for both groups (P < 0.05). In oral lichen planus, the number of single apoptotic bodies had a positive correlation with connective tissue granzyme immunostaining and a negative correlation with perforin (P<0.01). On the contrary, in oral cGVHD, the number of apoptotic body clusters presented a positive correlation with connective tissue perforin (P<0.01). CONCLUSIONS Our findings indicate that apoptosis in oral lichen planus seems to be correlated with granzyme B release, while in oral cGVHD, perforin seems to be more important. Although these diseases present clinical and histological similarities, subtle differences seem to exist in their pathogenetic mechanisms.
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Ding G, Wang W, Liu Y, Zhang C, Wang S. Mesenchymal stem cell transplantation: A potential therapy for oral lichen planus. Med Hypotheses 2011; 76:322-4. [DOI: 10.1016/j.mehy.2010.09.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2010] [Accepted: 09/19/2010] [Indexed: 01/01/2023]
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Mukae S, Okazaki Y, Tsuda H, Nagai K, Matsumoto N, Ochiai T, Oki H, Komiyama K. Detection of fascin and CCR-7 positive mature dendritic cells in oral lichen planus. J Oral Pathol Med 2009; 38:334-42. [PMID: 19243493 DOI: 10.1111/j.1600-0714.2008.00741.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Dendritic cells (DC) play a crucial role in the pathogenesis of oral lichen planus (OLP) with respect to antigens presented to T cells. We performed immunohistochemical analysis to elucidate the process of activation of DC in OLP. METHODS Thirty biopsy specimens were obtained from the patients with OLP. The expressions of CD1a, Langerin, S-100, fascin, chemokine receptor-7 (CCR-7), D2-40, cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) in DC from OLP and disease free control were investigated using specific antibodies. The distribution and number (1 mm(2)) of DC were assessed in the intra-epithelium and the submucosa specimens. Correlation between the number of DC and epithelium thickness was also determined. RESULT Immature DC (Langerin(+), CD1a(+), and S-100(+)) were identified in the epithelia from OLP patients and control, though the numbers of Langerin(+) and CD1a(+) positive cells were decreased in the OLP samples as compared to the control. Mature DC (fascin(+)) were identified in the submucosa specimens, not found in the epithelium from OLP or control. Double immunostaining revealed DC positive for fascin and CCR-7 in the submucosa, which had migrated into D2-40(+) lymph vessels. Furthermore, keratinocytes expressed both Prostaglandin E(2) (PGE(2)) converting enzymes, COX-2, and mPGES-1, indicating PGE(2) synthesis in the epithelial layer of the OLP specimens. CONCLUSION Our results indicate that DC change from immature to mature in the epithelium and are then drawn out to the submucosa. We demonstrate that mature DC localized in the submucosa, it consequently migrates into lymph vessels. This maturation process of DC is an important immunopathological feature of OLP.
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Affiliation(s)
- Shotaro Mukae
- Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan
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Orti-Raduan ÉSL, Nunes AJF, Oliveira DT, Lara VS, De Assis Taveira LA. Quantitative analysis of Langerhans’ cells in oral chronic graft-vs.-host disease. J Oral Pathol Med 2008; 38:132-7. [DOI: 10.1111/j.1600-0714.2008.00712.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Musso T, Scutera S, Vermi W, Daniele R, Fornaro M, Castagnoli C, Alotto D, Ravanini M, Cambieri I, Salogni L, Elia AR, Giovarelli M, Facchetti F, Girolomoni G, Sozzani S. Activin A induces Langerhans cell differentiation in vitro and in human skin explants. PLoS One 2008; 3:e3271. [PMID: 18813341 PMCID: PMC2533393 DOI: 10.1371/journal.pone.0003271] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2008] [Accepted: 09/01/2008] [Indexed: 12/30/2022] Open
Abstract
Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFbeta. In vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFbeta. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFbeta family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFbeta. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFbeta, responsible for LC differentiation during inflammatory/autoimmune conditions.
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Affiliation(s)
- Tiziana Musso
- Department of Public Health and Microbiology, University of Torino, Turin, Italy
| | - Sara Scutera
- Department of Public Health and Microbiology, University of Torino, Turin, Italy
| | - William Vermi
- Department of Pathology, University of Brescia, Brescia, Italy
| | - Roberta Daniele
- Section of General Pathology and Immunology, Department of Biomedical Sciences and Biotecnology, University of Brescia, Brescia, Italy
- Deparment of Dermatology, University of Verona, Verona, Italy
| | - Michele Fornaro
- Department of Clinical and Biological Sciences, San Luigi Hospital, University of Torino, Orbassano, Italy
| | - Carlotta Castagnoli
- Department of Plastic Surgery and Burn Unit Skin Bank, CTO Hospital, Turin, Italy
| | - Daniela Alotto
- Department of Plastic Surgery and Burn Unit Skin Bank, CTO Hospital, Turin, Italy
| | - Maria Ravanini
- Department of Pathology, University of Brescia, Brescia, Italy
| | - Irene Cambieri
- Department of Plastic Surgery and Burn Unit Skin Bank, CTO Hospital, Turin, Italy
| | - Laura Salogni
- Section of General Pathology and Immunology, Department of Biomedical Sciences and Biotecnology, University of Brescia, Brescia, Italy
| | - Angela Rita Elia
- Medicine and Experimental Oncology, and Clinical and Biological Sciences, University of Torino, Center for Experimental Research and Medical Studies (CERMS), S. Giovanni Battista Hospital, Turin, Italy
| | - Mirella Giovarelli
- Medicine and Experimental Oncology, and Clinical and Biological Sciences, University of Torino, Center for Experimental Research and Medical Studies (CERMS), S. Giovanni Battista Hospital, Turin, Italy
| | - Fabio Facchetti
- Department of Pathology, University of Brescia, Brescia, Italy
| | | | - Silvano Sozzani
- Section of General Pathology and Immunology, Department of Biomedical Sciences and Biotecnology, University of Brescia, Brescia, Italy
- * E-mail:
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Abstract
Hematopoietic cell transplantation is used to treat malignancies, hematologic and immune deficiency states, marrow failure syndromes, and autoimmune diseases. Graft-versus-host disease (GVHD) is a clinical syndrome seen following allogeneic transplantation where donorderived immunocompetent T cells and inflammatory responses attack host tissues. GVHD can cause significant morbidity and even result in mortality. The oral cavity is a frequently involved site with clinical changes resembling autoimmune collagen vascular diseases. Recognition, diagnosis, and monitoring of oral GVHD can help with diagnosis and grading of GVHD and judging responses to therapy. Topical and local management of symptomatic oral GVHD can reduce oral symptoms that can interfere with oral function and quality of life, and can reduce the need for more intensive immunosuppressive systemic therapies.
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Affiliation(s)
- Mark M Schubert
- Oral Medicine Service, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, 825 Eastlake Avenue East, Seattle, WA 98109, USA.
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Abstract
OBJECTIVE The objective of the present study was to compare a new type of symptomatic lichenoid reaction, specifically located on the mucosal side of the lips, and associated with microorganisms, with a matched group presenting with reticular oral lichen planus (OLP) of the buccal mucosa. PATIENTS AND METHODS The mean age for both groups was 66 years with a predominance of women (62%). The lichenoid reaction group (n = 25) presented with a reticular reaction pattern embracing various degrees of erythema. Patients presenting with OLP had similar lesions confined to the buccal mucosa but not on the mucosal side of the lips. RESULTS In both groups, 80% were on any type of medication. However, 56% of the patients with lichenoid reactions medicated with more than three drugs compared with 29% (P < 0.05) in the OLP group. The former group more often used medicaments prescribed for cardiovascular diseases (48%vs 25%). Twenty-two of the patients with lichenoid reactions were treated with chlorhexidine. In 80% of these patients (n = 18), the lesions improved or completely healed, indicating a microbial association. CONCLUSION Lichenoid reactions present on the mucosal side of the lips may be initiated by microbial plaque precipitated on the buccal surfaces of the anterior teeth.
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Affiliation(s)
- K Bäckman
- Clinic of Oral Medicine, Public Dental Health, Göteborg, Sweden
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Gustafson J, Eklund C, Wallström M, Zellin G, Magnusson B, Hasséus B. Langerin-expressing and CD83-expressing cells in oral lichen planus lesions. Acta Odontol Scand 2007; 65:156-61. [PMID: 17514517 DOI: 10.1080/00016350601137251] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE Dendritic Langerhans cells (LCs) have been attributed a role in the pathogenesis of lichen planus as autoantigen-presenting cells initiating expansion of autoreactive T cells. Langerin and CD83, which are cell molecules expressed on LCs, are associated with antigen presentation. The present study examined expression of Langerin and CD83 molecules on LCs in patients with oral lichen planus (OLP). MATERIAL AND METHODS Biopsies were obtained from seven patients with OLP. Oral mucosa from seven healthy subjects served as controls. Monoclonal antibodies (mAbs) were used in standard immunohistochemical procedures to visualize CD1a-, Langerin-, and CD83-molecule-expressing cells. RESULTS CD1a+ and Langerin+ cells were found in significantly higher frequencies in OLP epithelium compared with healthy oral epithelium (p<0.01 and p<0.05, respectively); however, the frequency of CD83+ cells did not differ (p>0.05). The connective tissue in OLP lesions showed significantly higher frequencies of CD1a+, Langerin+, and CD83+ cells compared with healthy connective tissue (p<0.01, p<0.01, and p<0.05). CD1a+ and Langerin+ cells in OLP and healthy epithelium had a dendritic morphology. CONCLUSIONS The study shows increased numbers of CD1a- and Langerin-expressing LCs in OLP compared with healthy controls. In the connective tissue, CD83+ cells with dendritic morphology were localized to regions of lymphocyte clusters. The presence of CD83+ dendritic cells in areas of lymphocyte clusters in the connective tissue of OLP lesions indicates the possibility of ongoing autoantigen presentation.
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Affiliation(s)
- Jenny Gustafson
- Section of Oral Immunology/Clinic for Oral Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
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Abstract
The mucosal lining of the respiratory and digestive systems contains the largest and most complex immune system in the body, but surprisingly little is known of the immune system that serves the oral mucosa. This review focuses on dendritic cells, particularly powerful arbiters of immunity, in response to antigens of microbial or tumor origin, but also of tolerance to self-antigens and commensal microbes. Although first discovered in 1868, the epidermal dendritic Langerhans cells remained enigmatic for over a century, until they were identified as the most peripheral outpost of the immune system. Investigators' ability to isolate, enrich, and culture dendritic cells has led to an explosion in the field. Presented herein is a review of dendritic cell history, ontogeny, function, and phenotype, and the role of different dendritic cell subsets in the oral mucosa and its diseases. Particular emphasis is placed on the mechanisms of recognition and capture of microbes by dendritic cells. Also emphasized is how dendritic cells may regulate immunity/tolerance in response to oral microbes.
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Affiliation(s)
- C W Cutler
- Department of Periodontics, 110 Rockland Hall, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8703, USA.
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Ebrahimi M, Wahlin YB, Coates PJ, Sjöström B, Nylander K. Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation. J Oral Pathol Med 2006; 35:46-50. [PMID: 16393253 DOI: 10.1111/j.1600-0714.2005.00376.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. METHODS Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. RESULTS In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. CONCLUSIONS Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms has been seen, indicating that this could lead to neoplastic transformation.
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Soares AB, Faria PR, Magna LA, Correa MEP, de Sousa CA, Almeida OP, Cintra ML. Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients. J Oral Pathol Med 2005; 34:368-73. [PMID: 15946186 DOI: 10.1111/j.1600-0714.2005.00322.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.
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Affiliation(s)
- A B Soares
- Department of Oral Pathology, State University of Campinas, Campinas-SP, Brazil.
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Demarosi F, Lodi G, Carrassi A, Soligo D, Sardella A. Oral malignancies following HSCT: graft versus host disease and other risk factors. Oral Oncol 2005; 41:865-77. [PMID: 16084755 DOI: 10.1016/j.oraloncology.2005.02.001] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2005] [Accepted: 02/02/2005] [Indexed: 01/18/2023]
Abstract
Allogenic hematopoietic stem cell transplantation (HSCT), a procedure that is widely used in the treatment of a large number of malignant and non-malignant hematological diseases, is still associated with a wide range of complications, one of the most important of which is graft versus host disease (GVHD). The patients undergoing allogenic HSCT are also at high risk of developing secondary neoplasms, particularly leukemias and lymphomas. Solid tumors are less frequent, and the incidence appears to increase over time; the most frequent solid tumors are squamous cell carcinomas. We found that almost all studies of solid cancers occurring after transplantation are based on relatively small numbers of cases which have been monitored for short periods, and little information is available on individual cancers. In particular, reports of oral cancers in HSCT are very few. Potential risk factors associated with the development of secondary solid cancers after HSCT have been well described. They include graft versus host disease (GVHD), preoperative regimens, with either radio-chemotherapy or chemotherapy alone, conditioning regimes, immunosuppressive GVHD prophylaxis, viral infection and chronic stimulation as a result of viral antigens, antigenic stimulation from histocompatibility differences between recipient and donor, primary diagnosis, interaction of any of these factors with genetic predisposition, and other factors such as sex and age. All patients treated with HSCT should therefore be closely followed over the long term with the aim of identifying the onset of secondary tumors as early as possible.
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Affiliation(s)
- Federica Demarosi
- Universita degli Studi di Milano, Dipartimento di Medicina, Chirurgia e Odontoiatria, Via Beldiletto 1/3, 20142 Milano, Italy.
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Santoro A, Majorana A, Roversi L, Gentili F, Marrelli S, Vermi W, Bardellini E, Sapelli P, Facchetti F. Recruitment of dendritic cells in oral lichen planus. J Pathol 2005; 205:426-34. [PMID: 15714455 DOI: 10.1002/path.1699] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Using immunohistochemistry the presence of different dendritic cell (DC) subsets was analysed in 16 biopsies from patients with oral lichen planus (OLP). A significant increase of CD1a+/Langerin+ Langerhans cells, DC-SIGN+ DC and CD123+/BDCA2+ plasmacytoid DCs (PDCs) was found in the epithelium and in the stroma of OLP biopsies compared to normal oral mucosa. A proportion of DCs were mature DC-LAMP+ and expressed S100 or CD11c, typically found in the interdigitating DCs of nodal T-cell areas. Double staining revealed that mature DCs co-expressed CCR7, thus indicating the development of a nodal migratory phenotype upon maturation. Significant recruitment of PDCs producing IFN-alpha was demonstrated by the expression of MxA within the lichenoid inflammatory infiltrate and close cell-to-cell contacts between PDCs and mature DCs were observed, with a significant correlation between the numbers of these two populations. Moreover, PDCs were also found to contain Granzyme-B, an associated-cytotoxic granule protein, inducing target cell apoptosis. Taken together, these results suggest that PDCs may promote maturation of DCs and amplify the cytotoxicity of lymphoid cells. Finally, the recruitment of different subtypes of DC, such as Langerhans cells, stromal DC-SIGN+ DCs and PDCs, associated with a significant proportion of mature DCs, acquiring a CCR7+ 'migratory' phenotype, indicate that they may play a pivotal role in the development of the lichenoid inflammatory infiltrate that occurs typically in OLP.
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MESH Headings
- Antigens, CD/analysis
- Antigens, CD1/analysis
- Antigens, Surface/analysis
- Cell Adhesion Molecules/analysis
- Dendritic Cells/chemistry
- Dendritic Cells/pathology
- Epithelial Cells/chemistry
- Epithelial Cells/pathology
- Fluorescent Antibody Technique/methods
- Humans
- Immunohistochemistry/methods
- Interleukin-3 Receptor alpha Subunit
- Langerhans Cells/chemistry
- Langerhans Cells/pathology
- Lectins, C-Type/analysis
- Lichen Planus, Oral/metabolism
- Lichen Planus, Oral/pathology
- Lysosomal Membrane Proteins
- Mannose-Binding Lectins/analysis
- Membrane Glycoproteins
- Mouth Mucosa/chemistry
- Mouth Mucosa/pathology
- Nerve Tissue Proteins/analysis
- Phenotype
- Receptors, CCR7
- Receptors, Cell Surface/analysis
- Receptors, Chemokine/analysis
- Receptors, Immunologic
- Receptors, Interleukin-3/analysis
- Stromal Cells/chemistry
- Stromal Cells/pathology
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Affiliation(s)
- Amerigo Santoro
- Department of Pathology, University of Brescia, Spedali Civili Brescia, Brescia, Italy
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DeRossi SS, Ciarrocca KN. Lichen planus, lichenoid drug reactions, and lichenoid mucositis. Dent Clin North Am 2005; 49:77-89, viii. [PMID: 15567362 DOI: 10.1016/j.cden.2004.08.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Lichen planus is a common mucocutaneous disease affecting a significant portion of the general population. This article reviews the most current concepts on the epidemiology, etiology, pathogenesis, clinical presentations, and treatment of oral lichen planus, lichenoid drug reactions, and lichenoid mucositis.
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Affiliation(s)
- Scott S DeRossi
- Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA 19104, USA.
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Eckardt A, Starke O, Stadler M, Reuter C, Hertenstein B. Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. Oral Oncol 2004; 40:811-4. [PMID: 15288836 DOI: 10.1016/j.oraloncology.2004.02.003] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2004] [Accepted: 02/05/2004] [Indexed: 10/26/2022]
Abstract
Oral involvement of chronic graft-versus-host disease (GvHD) is a most distressing and disabling complication of hematopoietic cell transplantation, for which systemic immunosuppression as well as topical corticosteroid treatment may offer only limited symptomatic relief. Here we report encouraging preliminary results with the application of tacrolimus (FK-506) as a 0.1% ointment in three patients with severe oral chronic GvHD, heavily pretreated without success, who experienced rapid, consistent, complete or at least marked, subjective and objective improvement with topical tacrolimus.
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Affiliation(s)
- André Eckardt
- Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
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Yamanaka Y, Akiyama M, Shibaki A, Kikuchi T, Shimizu H. Annular lichen planus: study of the cellular mechanisms of annularity. Dermatology 2004; 208:335-8. [PMID: 15178917 DOI: 10.1159/000077843] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2003] [Accepted: 12/12/2003] [Indexed: 11/19/2022] Open
Abstract
Annular lichen planus is a rare, unique subtype of lichen planus. We report a 34-year-old Japanese male who had multiple, dark red to purple, annular macules with slightly raised borders. Histopathological examination of a skin biopsy specimen from the peripheral region of the macule showed the typical features of lichen planus. Immunohistochemical stainings revealed that a number of CD1a-positive, S-100-protein-positive Langerhans cells were present at the border zone of the annular lesion and most of the infiltrating cells were CD4-positive, CD8-negative lymphocytes. Conversely, inside the annular lesion, the number of Langerhans cells was decreased, and an equal number of CD4-positive cells and CD8-positive cells was present in the sparse infiltration. These results suggest that activation of Langerhans cells initiated a lichenoid tissue reaction but a subsequent depletion of Langerhans cells suppressed the lymphocyte infiltration. These sequential events might be involved in the formation of the unique annular structure in this condition.
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Affiliation(s)
- Yasuko Yamanaka
- Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. ACTA ACUST UNITED AC 2004; 98:60-8. [PMID: 15243472 DOI: 10.1016/j.tripleo.2003.11.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES The aim of this study was to investigate the relationship between oral lichen planus and dry mouth by comparing xerostomia scores of individuals with oral lichen planus to those of healthy matched controls. STUDY DESIGN Patients who had attended 1 of 2 centers for the management of oral lichen planus (n=116), along with age- and sex-matched control subjects (n=348), were sent a questionnaire. Nonresponders were invited to complete the questionnaire by telephone in lieu of mailing a reply. A standardized medical history was obtained for all subjects. RESULTS The difference between patients with oral lichen planus and control subjects for all xerostomia questions was statistically significant. In the lichen planus group, the mean xerostomia score was 20.4, whereas for control patients, the mean score was 14.7 (P <.001). Stepwise conditional logistic regression analysis for the matched case-control groups was performed. CONCLUSION The results demonstrate an association between oral lichen planus and xerostomia in some individuals.
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Affiliation(s)
- Angus N Colquhoun
- Department of Stomatology, University of Otago, PO Box 647, Dunedin, New Zealand.
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