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Kakodkar P, Shekari N, Mainra R, Webster D, Pearce T, Wu F, Mostafa A. Vaccine-induced donor-specific HLA antibodies: a case report highlighting sensitization risks in renal transplant waitlisted patients. Front Immunol 2025; 16:1567377. [PMID: 40160827 PMCID: PMC11949935 DOI: 10.3389/fimmu.2025.1567377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 02/27/2025] [Indexed: 04/02/2025] Open
Abstract
Background In renal transplant waitlisted patients, vaccinations remain the standard of care for infection prevention. The vaccine and its adjuvant sensitizer can be potential sources for the induction of donor-specific antibodies (DSA) against human leukocyte antigens (HLA). These novel HLA antibodies can result in a positive flow cell crossmatch (FCXM), which can make a previously compatible live donor incompatible. Case report We present an adult renal transplant waitlisted patient who has had multiple negative T-cell and B-cell FCXM with no detection of DSA at baseline. The patient then received a single dose of pneumococcal conjugate (PCV13) and a second dose of recombinant zoster vaccine (RZV). After these vaccinations, the patient's FCXM was positive for both T-cells and B-cells and the HLA class I antibodies (A1, 23, 24, 80; B44, 45, 76) showed a calculated panel reactive antibody (cPRA) of 51%. A1 and B44 DSA were detected which predicted incompatibility with the patient's planned live donor renal transplant. The patient had to enter the kidney-paired donation program instead and receive their transplantation after 16 months. Conclusion RZV or PCV13 vaccines or their adjuvant components can potentially cause allosensitization in renal transplant waitlisted patients. The detection of DSA can result in reduced access to compatible transplants. With advances in HLA immunogenetics, better tools can monitor HLA-specific memory B-cells to provide crucial insights into the primary mechanism of action of HLA DSA antibody formation and suggest interventions to mitigate this memory B-cell activation.
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Affiliation(s)
- Pramath Kakodkar
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Nooshin Shekari
- Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada
| | - Rahul Mainra
- Division of Nephrology, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Destinie Webster
- Histocompatibility and Immunogenetics Laboratory, St. Paul’s Hospital, Saskatoon, SK, Canada
| | - Twyla Pearce
- Histocompatibility and Immunogenetics Laboratory, St. Paul’s Hospital, Saskatoon, SK, Canada
| | - Fang Wu
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Ahmed Mostafa
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- Histocompatibility and Immunogenetics Laboratory, St. Paul’s Hospital, Saskatoon, SK, Canada
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2
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Velikova T, Gerasoudis S, Batselova H. Vaccination for solid organ transplanted patients: Recommendations, efficacy, and safety. World J Transplant 2024; 14:92172. [PMID: 39697451 PMCID: PMC11438943 DOI: 10.5500/wjt.v14.i4.92172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 05/12/2024] [Accepted: 07/10/2024] [Indexed: 09/20/2024] Open
Abstract
Solid organ transplant recipients face unique challenges in managing their immunosuppressed status, making vaccination a critical consideration. This review aimed to comprehensively analyze current recommendations, evaluate the efficacy of vaccinations in this population, and assess safety concerns. We explored the latest evidence on vaccine types, timing, and potential benefits for transplant patients, highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 vaccines. By synthesizing available data, this review underscored the pressing need to optimize vaccination strategies, ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.
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Affiliation(s)
- Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
| | | | - Hristiana Batselova
- Department of Epidemiology and Disaster Medicine, Medical University, University Hospital “St George”, Plovdiv 4000, Bulgaria
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3
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Dukat-Mazurek A, Karolak W, Zielińska H, Moszkowska G, Wojarski J, Lipka K, Fercho J, Gallas M, Rystwej D, Sunesson F, Akily L, Karlsen W, Sawczuk M, Stachowicz-Chojnacka K, Nojek R, Żegleń S. Anti-HLA Immunization in Patients After Lung Transplantation: A Comparative Study Before and During the Pandemic. Transplant Proc 2024; 56:885-891. [PMID: 38729828 DOI: 10.1016/j.transproceed.2024.03.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 03/29/2024] [Indexed: 05/12/2024]
Abstract
Anti-human leukocyte antigen (anti-HLA) sensitization in lung transplant recipients (LTRs) can significantly impact graft survival and patient outcomes. The global pandemic, induced by the SARS-CoV-2 virus, brought about numerous challenges in the medical sphere, including potential alterations in HLA immunization patterns among LTRs. A retrospective analysis of LTRs group transplanted from July 2018 to 1 March 2020 (pre-pandemic) was compared with patients transplanted from 1 March 2020 to December 2022 (during the pandemic). Totally 92 patients were controlled. Patients were also divided into 2 groups: vaccinated and non-vaccinated. The results of cytotoxic crossmatch, results of anti-HLA antibody testing, presence of DSA before and after transplantation, and early and late graft function were compared between groups. In the pandemic and vaccinated groups, an increase was observed in the number of positive crossmatch tests performed with a pool of B lymphocytes. However, the presence of dithiothreitol abolished the positive reaction in 90% of cases. We also observed an increased percentage of patients immunized based on the results of solid phase tests both in the pandemic group and in the group of patients who received vaccination against the SARS-CoV-2 virus. It might be that the pandemic/vaccination has influenced the prevalence of anti-HLA immunization in LTRs. Further studies are essential to establish causative factors and develop targeted interventions for this population of patients.
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Affiliation(s)
| | - Wojtek Karolak
- Department of Cardiac Surgery, Medical University of Gdansk, Poland
| | - Hanna Zielińska
- Department of Medical Immunology, Medical University of Gdansk, Poland
| | | | - Jacek Wojarski
- Department of Cardiac Surgery, Medical University of Gdansk, Poland
| | - Karolina Lipka
- Department of Cardiac Surgery, Medical University of Gdansk, Poland
| | - Justyna Fercho
- Department of Neurosurgery, Medical University of Gdansk, Poland
| | - Marta Gallas
- Department of Cardiac Surgery, Medical University of Gdansk, Poland
| | - Dariusz Rystwej
- Faculty of Health Sciences with the Institute of Maritime and Tropical Medicine, Medical University of Gdansk, Poland
| | - Fanny Sunesson
- Emergency Department of Surgery (KAVA), Centralsjukhuset Kristianstad (CSK), Sweden
| | - Lin Akily
- Department of Pneumonology and Allergology, Medical University of Gdansk, Poland
| | - William Karlsen
- Department of Pneumonology and Allergology, Medical University of Gdansk, Poland
| | - Marcin Sawczuk
- Department of Pneumonology and Allergology, Medical University of Gdansk, Poland
| | | | - Rafał Nojek
- Department of Applied Computer Science, AGH University of Science and Technology in Krakow, Poland
| | - Sławomir Żegleń
- Department of Pneumonology and Allergology, Medical University of Gdansk, Poland.
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Xu Q, Zeevi A, Ganoza A, Cruz RJ, Mazariegos GV. Current approaches for risk assessment of intestinal transplant patients: A view from the histocompatibility laboratory. Hum Immunol 2024; 85:110768. [PMID: 38433035 DOI: 10.1016/j.humimm.2024.110768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/12/2024] [Accepted: 02/21/2024] [Indexed: 03/05/2024]
Abstract
Despite its recent decline in volumes, intestinal transplantation remains an important option for patients with irreversible intestinal failures. The long-term outcome of an intestinal transplant has stagnated. The major cause of graft loss is rejection, resulting from mismatches in human leukocyte antigens (HLA) and the presence of antibodies to mismatched donor-specific HLA antigens (DSA). Literature has reported that DSAs, either preformed before transplantation or developed de novo after transplantation, are harmful to intestinal grafts, especially for those without combined liver grafts. A comprehensive assessment of DSA by the histocompatibility laboratory is critical for successful intestinal transplantation and its long-term survival. This paper briefly reviews the history and current status of different methods for detecting DSA and their clinical applications in intestinal transplantation. The focus is on applying different antibody assays to manage immunologically challenging intestinal transplant patients before and after transplantation. A clinical case is presented to illustrate the complexity of HLA tests and the necessity of multiple assays. The review of risk assessment by the histocompatibility laboratory also highlights the need for close interaction between the laboratory and the intestinal transplant program.
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Affiliation(s)
- Qingyong Xu
- Department of Pathology, University of Pittsburgh, USA.
| | - Adriana Zeevi
- Department of Pathology, University of Pittsburgh, USA
| | | | - Ruy J Cruz
- Department of Surgery, University of Pittsburgh, USA; Gastrointestinal Rehabilitation and Transplant Center, Starzl Transplantation Institute, USA
| | - George V Mazariegos
- Department of Surgery, University of Pittsburgh, USA; Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, USA
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Al Attas RA, AlDhafir R, Mohammed A, AlAbduladheem D, Awaji M, AlAjlan K, AlOtaibi A, Bamrdouf R, Alabadi A. Impact of COVID-19 pandemic on transplant laboratories: How to mitigate? Heliyon 2024; 10:e26419. [PMID: 38404840 PMCID: PMC10884516 DOI: 10.1016/j.heliyon.2024.e26419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 02/13/2024] [Accepted: 02/13/2024] [Indexed: 02/27/2024] Open
Abstract
A positive flow cytometry crossmatch (FCXM) due to donor specific antibodies (DSA) constitutes a risk for kidney transplantation; such a finding may indicates an unacceptable donor for this patient. However, positive FCXM in the absence of DSA is considered discordant and need further investigations. During COVID-19 pandemic, we observed 22% discordant results out of 445 FCXM performed during eight months period in our laboratory and another 7% were invalid due to high background negative control (NC). No study has addressed the impact of COVID-19 pandemic on FCXM and the overall pre-kidney transplant workups or described a solution to deal with these non-specific reactivities. Herein, we analyzed all FCXM results in SARS-CoV-2 seropositive patients and addressed how this pandemic affected significantly the pre-kidney transplant workups, highlighting both technical and financial implications. We also shared our modified FCXM procedures using dithiotheritol (DTT) sera treatment or blocking donor cells with negative control human serum (NCS) which we found to be successful to abrogate 98% of all discordant FCXM results and to validate all invalid results due to high background NC. In conclusion, COVID-19 pandemic has affected our HLA laboratory significantly by creating many false positive or invalid crossmatch results. Transplant laboratories must consider this before test interpretations and immune risk assessments. We recommend the use of DTT serum treatment to remove nonspecific bindings in the sera of kidney transplant candidates and the use of NCS-blocked donor cells to correct high background when performing FCXM in transplant candidates or donors with recent history of SARS-CoV-2 immunization respectively.
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Affiliation(s)
- Rabab Ali Al Attas
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Raha AlDhafir
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Amani Mohammed
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Dalal AlAbduladheem
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Mohammad Awaji
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Kenana AlAjlan
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Ahmed AlOtaibi
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Rafah Bamrdouf
- Histocompatibility& Immunoigenetics (HIL), Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
| | - Abdulnaser Alabadi
- Multiorgan Transplant Division, King Fahad Specialist Hospital-Dammam (KFSH-D), Saudi Arabia
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6
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Abu-Khader A, Hu Q, Kamar F, Galaszkiewicz I, Wang W, Khan F, Berka N. Low incidence of de novo HLA antibodies after COVID-19 vaccination: A cohort study of patients awaiting kidney transplantation. Transpl Infect Dis 2023; 25:e14105. [PMID: 37650468 DOI: 10.1111/tid.14105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 06/17/2023] [Accepted: 07/05/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Antibodies against human leukocyte antigen (anti-HLA Abs) are associated with an increased risk of allograft loss. Herein, we report the prospective follow-up for anti-HLA Abs formation in 103 patients with end-stage kidney disease on the waiting list for transplantation who underwent COVID-19 vaccination. PATIENTS AND METHODS Sera were tested before and after vaccination using Luminex technology. The cohort comprised of 62 males and 41 females with a mean age of 56 ± 14 years. The patients received BNT162b2 (80.4%), mRNA-1273 (18.5%), AZD1222 (0.40%), or ChAdOx1-S (0.80%) vaccine. Patients were tested before and within 119 ± 50, 95 ± 46 and 25 ± 26 days after the first, second, and third dose of the vaccine, respectively. RESULTS No significant change in calculated panel reactive antibody (cPRA) after vaccination was seen. Although 98.1% of patients had no change in anti-HLA Abs profile or cPRA after vaccination, two patients (1.9%) developed de novo anti-HLA Abs against class I or II HLA antigens. In those two patients, the cPRA changed from 0% and 63% at baseline to 9% and 90% after vaccination, respectively. Both patients received the BNT162b2 mRNA-based vaccine. The earliest detected anti-HLA Abs was 18 days after the first dose. CONCLUSION In rare cases, new anti-HLA antibodies were observed after COVID-19 vaccination, with potential implications for transplantation. The low incidence of this phenomenon is outweighed by the clinical benefits of vaccination.
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Affiliation(s)
- Ahmad Abu-Khader
- Transplant Immunology and Histocompatibility Laboratory, Department of Pathology, University of Texas Southwestern Medical Center, Texas, USA
| | - Qian Hu
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada
- Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Fareed Kamar
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Iwona Galaszkiewicz
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada
| | - Wenjie Wang
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Faisal Khan
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada
- Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Noureddine Berka
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada
- Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
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7
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Choi S, Lee H, Eum SH, Min JW, Yoon HE, Yang CW, Chung BH. Severity of COVID-19 Pneumonia in Kidney Transplant Recipients According to SARS-CoV-2 Vaccination. Infect Chemother 2023; 55:505-509. [PMID: 38183395 PMCID: PMC10771954 DOI: 10.3947/ic.2023.0083] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/20/2023] [Indexed: 01/08/2024] Open
Abstract
We reviewed 24 kidney transplantat recipients (KTRs) who had radiologically confirmed coronavirus disease 2019 (COVID-19) pneumonia. Enrolled KTRs were divided into a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-vaccination (+) group (n = 18) and a vaccination (-) group (n = 6). Clinical outcomes of the two groups including death, pulmonary outcome, and renal outcome were compared. COVID-19 pneumonia was worse in vaccination (-) KTRs. Two out of six vaccination (-) KTRs needed continuous renal replacement therapy (CRRT) and mechanical ventilator (MV) and expired. In contrast, only one KTR expired and required CRRT and MV out of 18 vaccination (+) KTRs. Our results suggest that SARS-CoV-2 vaccination attenuates severity of COVID-19 pneumonia in KTRs.
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Affiliation(s)
- Seunghyeok Choi
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hanbi Lee
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang Hun Eum
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji-Won Min
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hye Eun Yoon
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Woo Yang
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Byung Ha Chung
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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8
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DeFilippis EM, Kransdorf EP, Jaiswal A, Zhang X, Patel J, Kobashigawa JA, Baran DA, Kittleson MM. Detection and management of HLA sensitization in candidates for adult heart transplantation. J Heart Lung Transplant 2023; 42:409-422. [PMID: 36631340 DOI: 10.1016/j.healun.2022.12.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 12/13/2022] [Accepted: 12/17/2022] [Indexed: 12/28/2022] Open
Abstract
Heart transplantation (HT) remains the preferred therapy for patients with advanced heart failure. However, for sensitized HT candidates who have antibodies to human leukocyte antigens , finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting HT has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. This State-of-the-Art review discusses the assessment of human leukocyte antigens antibodies, potential desensitization strategies including mechanisms of action and specific protocols, the approach to a potential donor including the use of complement-dependent cytotoxicity, flow cytometry, and virtual crossmatches, and peritransplant induction management.
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Affiliation(s)
- Ersilia M DeFilippis
- Center for Advanced Cardiac Care, Division of Cardiology, Columbia University Irving Medical Center, New York, New York
| | - Evan P Kransdorf
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Abhishek Jaiswal
- Hartford HealthCare Heart and Vascular Institute, Hartford Hospital, Hartford, Connecticut
| | - Xiaohai Zhang
- HLA and Immunogenetics Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jignesh Patel
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jon A Kobashigawa
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - David A Baran
- Cleveland Clinic, Heart Vascular and Thoracic Institute, Weston, Florida
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9
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Puttarajappa CM, Tevar AD, Hoffman W, Degenholtz H, Schinstock CA, Gunabushanam V, Zeevi A, Xu Q, Hariharan S. Virtual crossmatch for deceased donor kidney transplantation in the United States: A survey of histocompatibility lab directors and transplant surgeons. Hum Immunol 2023; 84:214-223. [PMID: 36581507 PMCID: PMC9991979 DOI: 10.1016/j.humimm.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/22/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022]
Abstract
Virtual crossmatch (VXM) is used as an alternative to or in conjunction with a cell-based physical crossmatch (PXM) for assessing HLA (human leukocyte antigen) compatibility prior to deceased donor kidney transplantation (DDKT). Data on practice patterns and perceptions regarding VXM use in the US are limited. We performed a survey of US HLA directors and transplant surgeons regarding HLA testing and crossmatch strategies. 53 (56 %) HLA directors and 68 surgeons (representing ∼ 23 % of US transplant centers) completed the survey. Both groups agreed that VXM could reduce cold ischemia time (CIT), costs and improve allocation efficiency. VXM use increased following the 2021 kidney allocation change. Reducing CIT was the primary reason for favoring VXM over PXM. Preference for VXM reduced as candidates' panel reactive antibodies increased. Regulations, program policies and limitations of HLA technology were cited as important reasons for preferring PXM over VXM. Surgeons reported similar perceptions, but findings are limited by the low response rate. Finally, half the labs reported lacking specific protocols for VXM use. In conclusion, improved HLA technology and protocols along with changes to institutional procedures and policy regulations are needed for safer expansion of VXM in DDKT.
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Affiliation(s)
- Chethan M Puttarajappa
- Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, USA.
| | - Amit D Tevar
- Department of Surgery, University of Pittsburgh, Pittsburgh, USA
| | | | - Howard Degenholtz
- Department of Health Policy and Management, University of Pittsburgh, Pittsburgh, USA
| | | | | | - Adriana Zeevi
- Department of Pathology, University of Pittsburgh, Pittsburgh, USA
| | - Qingyong Xu
- Department of Pathology, University of Pittsburgh, Pittsburgh, USA
| | - Sundaram Hariharan
- Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, USA
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10
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Roll GR, Bray RA, Cooper M, Eagar TN, Gebel HM, Vranic GM, Hitchman KM, Houp J, Kamoun M, Killian J, Kim J, Kumar V, Levine M, Lovasik BP, Lunow-Luke T, Parsons RF, Pattanayak V, Ranch D, Shah A, Stock PG, Timofeeva OA, Trofe-Clark J, Wongjirad C, Yeh H, Yi S, Rajalingam R. COVID-19 infection and vaccination rarely impact HLA antibody profile in waitlisted renal transplant Candidates- a multicenter cohort. Hum Immunol 2023; 84:278-285. [PMID: 36868898 PMCID: PMC9946887 DOI: 10.1016/j.humimm.2023.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 02/18/2023] [Accepted: 02/20/2023] [Indexed: 02/25/2023]
Abstract
Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers' cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs.
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Affiliation(s)
- Garrett R. Roll
- Department of Surgery, University of California San Francisco, San Francisco, CA, United States
| | - Robert A. Bray
- Histocompatibility and Molecular Immunogenetics Laboratory, Emory University, Atlanta, GA, United States
| | - Matthew Cooper
- Medstar-Georgetown Transplant Institute, Washington, DC, United States
| | - Todd N. Eagar
- Immunogenetics and Transplantation Laboratory Houston Methodist, Houston, TX, United States
| | - Howard M. Gebel
- Histocompatibility and Molecular Immunogenetics Laboratory, Emory University, Atlanta, GA, United States
| | - Gayle M. Vranic
- Medstar-Georgetown Transplant Institute, Washington, DC, United States
| | - Kelley M.K. Hitchman
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, San Antonio, San Antonio, TX, United States
| | - Julie Houp
- Department of Laboratory Medicine, University of Alabama Medical Center, Birmingham, AL, United Kingdom
| | - Malek Kamoun
- Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, United States
| | - John Killian
- Department of Surgery, University of Alabama Medical Center, Birmingham, AL, United Kingdom
| | - Jim Kim
- Department of Surgery, University of Southern California, Los Angeles, CA, United States
| | - Vineeta Kumar
- Department of Medicine, Division of Nephrology, University of Alabama, Birmingham, AL, United Kingdom
| | - Matthew Levine
- Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, United States
| | - Brendan P. Lovasik
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States
| | - Tyler Lunow-Luke
- Department of Surgery, University of California San Francisco, San Francisco, CA, United States
| | - Ronald F. Parsons
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States
| | - Vikram Pattanayak
- Department of Pathology, Massachusetts General Hospital, Boston MA, United States
| | - Daniel Ranch
- Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Anushi Shah
- Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Peter G. Stock
- Department of Surgery, University of California San Francisco, San Francisco, CA, United States
| | - Olga A. Timofeeva
- Department of Pathology, MedStar Georgetown University Hospital, Washington, DC, United States
| | - Jennifer Trofe-Clark
- Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, United States
| | - Chelsey Wongjirad
- Department of Surgery, University of Southern California, Los Angeles, CA, United States
| | - Heidi Yeh
- Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Stephanie Yi
- Department of Surgery, Houston Methodist, Houston, TX, United States
| | - Raja Rajalingam
- Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, United States.
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11
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Awaji M, Alajlan K, Shaikh A, Alkebasi S, Kutty C, Alshami A, Attas RAA. HLA Sensitization in the Era of COVID-19: Single-Center Experience. Transplant Proc 2022; 54:2658-2662. [PMID: 36372565 PMCID: PMC9537251 DOI: 10.1016/j.transproceed.2022.10.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/28/2022] [Accepted: 10/03/2022] [Indexed: 11/07/2022]
Abstract
It is well known that several viral infections are capable of triggering the formation of HLA antibodies; however, an association between SARS-CoV-2 and the development of anti-HLA antibodies is not yet confirmed. In this study, we compared the prevalence of HLA antibody before and after COVID-19 infection in a cohort of 3 groups included 58 healthy nonsensitized employees (HNEs), 130 kidney transplant recipients (KTRs), and 62 kidney transplant candidates. There were no significant changes observed in HLA class I antibodies in any of the groups, but evaluation of antibodies to HLA class II revealed a significant change in the KTR group (P = .0184) after acquiring COVID-19 infection and in the HNE group (P = .0043) when compared to the reported prevalence in a similar population. Although we observed the emergence of convalescent de novo donor-specific antibodies in 2 patients, we did not encounter any rejection episodes in the KTR group. Finally, the results of flow cytometry crossmatch in the HNE group were not consistent with the state of antibodies. In conclusion, COVID-19 infection has the potential to produce class II antibodies but with little effect on preexisting sensitization. These antibodies are likely to be transient and not necessarily causing positive crossmatch with the corresponding antigens at the proper mean fluorescent intensity and therefore should not affect access to transplantation. There is a need for further evaluation to ascertain the genuineness of these antibodies and their exact effect on transplant readiness and outcomes.
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Affiliation(s)
- Mohammad Awaji
- Histocompatibility & Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Kenana Alajlan
- Histocompatibility & Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Alaa Shaikh
- Molecular Diagnostics Laboratory, Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Shaima Alkebasi
- Histocompatibility & Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Clara Kutty
- Histocompatibility & Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Alanoud Alshami
- Division of Pediatric Nephrology and Kidney Transplant, Multiorgan Transplant Center, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Rabab Ali Al Attas
- Histocompatibility & Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia,Address correspondence to Rabab Ali Al Attas MD, F (ACHI), D (ABMLI), Consultant Immunopathologist & Immunogeneticist, Director, Histocompatibility & Immunogenetics Lab & Head, Immunology/Serology Laboratory, Department of Pathology and Lab Medicine, King Fahad Specialist Hospital-Dammam, Al Muraikibat, Amer Bin Thabit St., Building 6, Office 2, PO BOX 15215, Dammam 31444, MBC 35, Saudi Arabia. Tel: (+966) 138043333, ext. 6737, Fax: (+966) 138042222
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12
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Wijtvliet VPWM, Verheyden S, Depreter B, Heylen C, Coeman E, Abrams S, De Winter BY, Massart A, Hellemans R, Pipeleers L, Claas FHJ, Ariën KK, Wissing KM, Abramowicz D, Ledeganck KJ. SARS-CoV-2 mRNA vaccination is not associated with the induction of anti-HLA or non-HLA antibodies. Transpl Immunol 2022; 74:101670. [PMID: 35835296 PMCID: PMC9271456 DOI: 10.1016/j.trim.2022.101670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/07/2022] [Accepted: 07/08/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND SARS-CoV-2 vaccination is strongly recommended in kidney transplant recipients (KTR) and dialysis patients. Whether these vaccinations may trigger alloantibodies, is still debated. METHODS In the current study we evaluated the effect of SARS-CoV-2 mRNA vaccines on anti-Human Leukocyte Antigen (HLA) and 60 anti-non-HLA antibody profiles in clinically stable KTR and dialysis patients. In total, we included 28 KTR, 30 patients on haemodialysis, 25 patients on peritoneal dialysis and 31 controls with a positive seroresponse 16-21 days after the first dose of either the SARS-CoV-2 mRNA BNT162b2 or mRNA-1273 vaccine. Both anti-HLA and anti-non-HLA antibodies were determined prior to vaccination and 21 to 35 days after the second vaccine dose. RESULTS Overall, the proportion of patients with detectable anti-HLA antibodies was similar before and after vaccination (class I 14% vs. 16%, p = 0.48; class II 25% before and after vaccination). After vaccination, there was no pattern in 1) additionally detected anti-HLA antibodies, or 2) the levels of pre-existing ones. Additional anti-non-HLA antibodies were detected in 30% of the patients, ranging from 1 to 5 new anti-non-HLA antibodies per patient. However, the clinical significance of anti-non-HLA antibodies is still a matter of debate. To date, only a significant association has been found for anti-non-HLA ARHGDIB antibodies and long-term kidney graft loss. No additionally developed anti-ARHGDIB antibodies or elevated level of existing anti-ARHGDIB antibodies was observed. CONCLUSION The current data indicate that SARS-CoV-2 mRNA vaccination does not induce anti-HLA or anti-non-HLA antibodies, corroborating the importance of vaccinating KTR and dialysis patients.
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Affiliation(s)
- Veerle P W M Wijtvliet
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium; Department of Nephrology and Hypertension, Antwerp University Hospital, Edegem, Belgium.
| | - Sonja Verheyden
- Department of Hematology, HLA and Molecular Hematology Laboratory, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
| | - Barbara Depreter
- Department of Hematology, HLA and Molecular Hematology Laboratory, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
| | | | | | - Steven Abrams
- Department of Family Medicine and Population Health, Global Health Institute, University of Antwerp, Antwerp, Belgium; I-BioStat, Data Science Institute, Hasselt University, Diepenbeek, Belgium
| | - Benedicte Y De Winter
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium
| | - Annick Massart
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium; Department of Nephrology and Hypertension, Antwerp University Hospital, Edegem, Belgium
| | - Rachel Hellemans
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium; Department of Nephrology and Hypertension, Antwerp University Hospital, Edegem, Belgium
| | - Lissa Pipeleers
- Department of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Frans H J Claas
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium; Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
| | - Kevin K Ariën
- Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Karl Martin Wissing
- Department of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Daniel Abramowicz
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium; Department of Nephrology and Hypertension, Antwerp University Hospital, Edegem, Belgium
| | - Kristien J Ledeganck
- Laboratory of Experimental Medicine and Pediatrics and member of the Infla-Med Centre of Excellence, University of Antwerp, Edegem, Belgium
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13
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McCune TR, Bray RA, Baran DA, Toepp AJ, Forte SJ, Gilgannon LT, Williams T, Chen S, Sadr H, Gebel HM, Herre JM. Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients. Transpl Immunol 2022; 75:101722. [PMID: 36152939 PMCID: PMC9492402 DOI: 10.1016/j.trim.2022.101722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/12/2022] [Accepted: 09/14/2022] [Indexed: 11/25/2022]
Abstract
This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS).
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Affiliation(s)
- Thomas R McCune
- Eastern Virginia Medical School, Division of Nephrology, Norfolk, VA 23501-1980, USA; Sentara Norfolk General Hospital, Kidney/Pancreas Transplant Program, Norfolk, VA 23507, USA; Eastern Virginia Medical School, Department of Internal Medicine, Norfolk, VA 23501-1980, USA.
| | - Robert A Bray
- Emory Univ Hosp, Dept of Pathology Rm F149, 1364 Clifton Rd NE, Atlanta, GA 30322, USA.
| | - David A Baran
- Eastern Virginia Medical School, Division of Cardiology, Norfolk, VA 23501-1980, USA; Sentara Norfolk General Hospital, Advanced Heart Failure and Transplantation, Norfolk, VA 23507-1999, USA; Eastern Virginia Medical School, Department of Internal Medicine, Norfolk, VA 23501-1980, USA
| | - Angela J Toepp
- Sentara Healthcare, Quality Research Institute, Virginia Beach, VA 23462, USA; Enterprise Analytics, Sentara Healthcare, Norfolk, VA 23501, USA.
| | - Steven J Forte
- Eastern Virginia Medical School, School of Medicine, Norfolk, VA 23501-1980, USA.
| | - Lauren T Gilgannon
- Eastern Virginia Medical School, School of Medicine, Norfolk, VA 23501-1980, USA.
| | - Troy Williams
- Enterprise Analytics, Sentara Healthcare, Norfolk, VA 23501, USA.
| | - Shirui Chen
- Eastern Virginia Medical School, Division of Nephrology, Norfolk, VA 23501-1980, USA
| | - Hooman Sadr
- Sentara Norfolk General Hospital, Kidney/Pancreas Transplant Program, Norfolk, VA 23507, USA
| | - Howard M Gebel
- Emory Univ Hosp, Dept of Pathology Rm F149, 1364 Clifton Rd NE, Atlanta, GA 30322, USA.
| | - John M Herre
- Eastern Virginia Medical School, Division of Cardiology, Norfolk, VA 23501-1980, USA; Sentara Norfolk General Hospital, Advanced Heart Failure and Transplantation, Norfolk, VA 23507-1999, USA; Eastern Virginia Medical School, Department of Internal Medicine, Norfolk, VA 23501-1980, USA.
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14
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Kim JK, Bae H, Ko GY, Lee J, Jung J, Jekarl DW, Choi AR, Lee S, Chung BH, Yang CW, Park SC, Oh EJ. Successful ABO-incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch-positive donor-specific class I HLA antibodies following COVID-19 vaccination. HLA 2022; 100:52-58. [PMID: 35484951 DOI: 10.1111/tan.14649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/29/2022] [Accepted: 04/26/2022] [Indexed: 11/28/2022]
Abstract
The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABO-incompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferon-gamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to two months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Jae Kwon Kim
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyunjoo Bae
- Department of Biomedical Science, Graduate School, the Catholic University of Korea, Seoul, Korea
| | - Geon Young Ko
- Department of Biomedical Science, Graduate School, the Catholic University of Korea, Seoul, Korea
| | - Jihyun Lee
- Department of Biomedical Science, Graduate School, the Catholic University of Korea, Seoul, Korea
| | - Jin Jung
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Research and Development Institute for In Vitro Diagnostic Medical Devices of Catholic University of Korea, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong Wook Jekarl
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Research and Development Institute for In Vitro Diagnostic Medical Devices of Catholic University of Korea, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ae-Ran Choi
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sangyoon Lee
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Byung Ha Chung
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Woo Yang
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sun Cheol Park
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun-Jee Oh
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Research and Development Institute for In Vitro Diagnostic Medical Devices of Catholic University of Korea, College of Medicine, The Catholic University of Korea, Seoul, Korea
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15
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Grupper A, Katchman H. SARS-CoV-2 Vaccines: Safety and Immunogenicity in Solid Organ Transplant Recipients and Strategies for Improving Vaccine Responses. CURRENT TRANSPLANTATION REPORTS 2022; 9:35-47. [PMID: 35096509 PMCID: PMC8783189 DOI: 10.1007/s40472-022-00359-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2021] [Indexed: 12/20/2022]
Abstract
Purpose of Review While solid organ transplant (SOT) recipients are at the highest risk for severe complications and increased mortality from COVID19 disease, their vaccination against SARS-CoV-2 remains challenging due to fear of immune-mediated adverse events and suboptimal immune response. Our current review is aimed to summarize current knowledge about the safety and efficacy of SARS-CoV-2 vaccines, describe factors that are correlated with immune response, and discuss strategies to improve vaccine immunogenicity in SOT recipients. Recent Findings SARS-CoV-2 vaccines are safe in SOT recipients and not related to rejection or other major adverse events. The immune response to two doses of vaccine is suboptimal and correlated to age and magnitude of immunosuppression. Administration of a third vaccine dose brings to significant amplification of immune response. Summary This review strengthens the existing recommendation of vaccination by three doses of vaccine in all SOT recipients and completion of vaccination before transplantation if possible.
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16
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Abu-Khader A, Wang W, Berka M, Galaszkiewicz I, Khan F, Berka N. SARS Cov-2 vaccination induces de novo donor-specific HLA antibodies in a renal transplant patient on waiting list: A case report. HLA 2021; 99:25-30. [PMID: 34791833 PMCID: PMC8661878 DOI: 10.1111/tan.14492] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/08/2021] [Accepted: 11/13/2021] [Indexed: 01/11/2023]
Abstract
The ability of COVID‐19 vaccination to induce anti‐HLA antibodies (Abs) formation in renal transplant candidates is not well studied. A 42‐year‐old man on a renal transplant waitlist, with no sensitization history, was tested for DSA before and after COVID‐19 vaccination. Patient has consistently tested negative for COVID‐19 virus. Eighteen days after receiving first dose of mRNA‐based vaccine, flow cytometry crossmatch (FCXM) was strongly positive with de novo donor‐specific Ab (dnDSA) against B57 and de novo non‐DSA against B58. Before vaccination, preliminary FCXM was negative with no anti‐HLA Abs. This event prompted the transplant team to cancel the surgery. COVID‐19 vaccination could be associated with anti‐HLA Abs formation in renal patients on waitlists that could affect future transplantability.
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Affiliation(s)
- Ahmad Abu-Khader
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada.,Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada
| | - Wenjie Wang
- Department of Medicine, University of Calgary, Alberta, Canada
| | - Meriam Berka
- Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada
| | - Iwona Galaszkiewicz
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada
| | - Faisal Khan
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada.,Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada
| | - Noureddine Berka
- Histocompatibility and Immunogenetics Laboratory, Alberta Precision Laboratories, Alberta, Canada.,Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada
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