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Fang X, Cui S, Lee H, Min JW, Lim SW, Oh EJ, Yang CW, Shin YJ, Chung BH. Combined Use of Tocilizumab and Mesenchymal Stem Cells Attenuate the Development of an Anti-HLA-A2.1 Antibody in a Highly Sensitized Mouse Model. Int J Mol Sci 2024; 25:1378. [PMID: 38338657 PMCID: PMC10855827 DOI: 10.3390/ijms25031378] [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: 12/08/2023] [Revised: 01/10/2024] [Accepted: 01/15/2024] [Indexed: 02/12/2024] Open
Abstract
Sensitization to HLA can result in allograft loss for kidney transplantation (KT) patients. Therefore, it is required to develop an appropriate desensitization (DSZ) technique to remove HLA-donor-specific anti-HLA antibody (DSA) before KT. The aim of this research was to investigate whether combined use of the IL-6 receptor-blocking antibody, tocilizumab (TCZ), and bone-marrow-derived mesenchymal stem cells (BM-MSCs) could attenuate humoral immune responses in an allo-sensitized mouse model developed using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and treated with TCZ, BM-MSC, or both TCZ and BM-MSC. We compared HLA.A2-specific IgG levels and subsets of T cells and B cells using flow cytometry among groups. HLA.A2-specific IgG level was decreased in all treated groups in comparison with that in the allo-sensitized control (Allo-CONT) group. Its decrease was the most significant in the TCZ + BM-MSC group. Regarding the B cell subset, combined use of TCZ and BM-MSC increased proportions of pre-pro B cells but decreased proportions of mature B cells in BM (p < 0.05 vs. control). In the spleen, an increase in transitional memory was observed with a significant decrease in marginal, follicular, and long-lived plasma B cells (p < 0.05 vs. control) in the TCZ + BM-MSC group. In T cell subsets, Th2 and Th17 cells were significantly decreased, but Treg cells were significantly increased in the TCZ+BM-MSC group compared to those in the Allo-CONT group in the spleen. Regarding RNA levels, IL-10 and Foxp3 showed increased expression, whereas IL-23 and IFN-γ showed decreased expression in the TCZ + BM-MSC group. In conclusion, combined use of TCZ and BM-MSC can inhibit B cell maturation and up-regulate Treg cells, finally resulting in the reduction of HLA.A2-specific IgG in a highly sensitized mouse model. This study suggests that the combined use of TCZ and BM-MSC can be proposed as a novel strategy in a desensitization protocol for highly sensitized patients.
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Affiliation(s)
- Xianying Fang
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
| | - Sheng Cui
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
| | - Hanbi Lee
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Ji Won Min
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
- Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, Bucheon-si 14647, Republic of Korea
| | - Sun Woo Lim
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
| | - Eun-Jee Oh
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
- Department of Laboratory Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Chul Woo Yang
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Yoo Jin Shin
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
| | - Byung Ha Chung
- Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (X.F.); (S.C.); (H.L.); (J.W.M.); (S.W.L.); (E.-J.O.); (C.W.Y.)
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Lee H, Lee H, Eum SH, Ko EJ, Min JW, Oh EJ, Yang CW, Chung BH. Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients. Ann Lab Med 2023; 43:364-374. [PMID: 36843405 PMCID: PMC9989540 DOI: 10.3343/alm.2023.43.4.364] [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: 09/02/2022] [Revised: 12/07/2022] [Accepted: 01/27/2023] [Indexed: 02/28/2023] Open
Abstract
Background The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients. Methods We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary's Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA. Results The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79-51.56) than in LDKT (OR: 3.76, 95% CI: 0.99-14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA. Conclusions Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.
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Affiliation(s)
- Haeun Lee
- 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
| | - Sang Hun Eum
- Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Eun Jeong Ko
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Transplant Research Center, Convergent Research Consortium for Immunologic Disease, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji-Won Min
- Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
| | - Eun-Jee Oh
- Department of Laboratory 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.,Transplant Research Center, Convergent Research Consortium for Immunologic Disease, 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.,Transplant Research Center, Convergent Research Consortium for Immunologic Disease, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Aspectos técnicos y clínicos de la prueba cruzada de histocompatibilidad en el trasplante de órganos sólidos. BIOMÉDICA 2022; 42:391-413. [PMID: 35867930 PMCID: PMC9467682 DOI: 10.7705/biomedica.6255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Indexed: 11/21/2022]
Abstract
La presencia de anticuerpos dirigidos contra los antígenos leucocitarios humanos (Human Leukocyte Antigens, HLA) que se expresan en las células del donante, es uno de los factores de riesgo más importantes asociados con las complicaciones clínicas después del trasplante. La prueba cruzada es una de las pruebas de histocompatibilidad más eficaces para la detección de anticuerpos específicos contra el donante en los receptores de injertos. En los primeros métodos de la prueba cruzada, se utilizaba la citotoxicidad dependiente del complemento, que es útil para detectar dichos anticuerpos responsables del rechazo hiperagudo del injerto, pero carece de la sensibilidad adecuada. Por ello, se desarrollaron métodos de pruebas cruzadas más sensibles, entre ellas, la prueba cruzada por citometría de flujo que hoy se considera el método preferido. En este artículo se revisa la evolución de la prueba cruzada y los factores más importantes que deben tenerse en cuenta al realizarla y al interpretar los resultados de esta prueba fundamental para la supervivencia a largo plazo del injerto.
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Bery AI, Hachem RR. Antibody-mediated rejection after lung transplantation. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:411. [PMID: 32355855 PMCID: PMC7186640 DOI: 10.21037/atm.2019.11.86] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Antibody-mediated rejection (AMR) has been identified as a significant form of acute allograft dysfunction in lung transplantation. The development of consensus diagnostic criteria has created a uniform definition of AMR; however, significant limitations of these criteria have been identified. Treatment modalities for AMR have been adapted from other areas of medicine and data on the effectiveness of these therapies in AMR are limited. AMR is often refractory to these therapies, and graft failure and death are common. AMR is associated with increased rates of chronic lung allograft dysfunction (CLAD) and poor long-term survival. In this review, we discuss the history of AMR and describe known mechanisms, application of the consensus diagnostic criteria, data for current treatment strategies, and long-term outcomes. In addition, we highlight current gaps in knowledge, ongoing research, and future directions to address these gaps. Promising diagnostic techniques are actively being investigated that may allow for early detection and treatment of AMR. We conclude that further investigation is required to identify and define chronic and subclinical AMR, and head-to-head comparisons of currently used treatment protocols are necessary to identify an optimal treatment approach. Gaps in knowledge regarding the epidemiology, mechanisms, diagnosis, and treatment of AMR continue to exist and future research should focus on these aspects.
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Affiliation(s)
- Amit I Bery
- Division of Pulmonary & Critical Care, Washington University School of Medicine, Saint Louis, MO, USA
| | - Ramsey R Hachem
- Division of Pulmonary & Critical Care, Washington University School of Medicine, Saint Louis, MO, USA
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Althaf MM, El Kossi M, Jin JK, Sharma A, Halawa AM. Human leukocyte antigen typing and crossmatch: A comprehensive review. World J Transplant 2017; 7:339-348. [PMID: 29312863 PMCID: PMC5743871 DOI: 10.5500/wjt.v7.i6.339] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 08/22/2017] [Accepted: 10/17/2017] [Indexed: 02/05/2023] Open
Abstract
Renal transplantation remains the best option for patients suffering from end stage renal disease (ESRD). Given the worldwide shortage of organs and growing population of patients with ESRD, those waitlisted for a transplant is ever expanding. Contemporary crossmatch methods and human leukocyte antigen (HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients. Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome. Interpretation of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant immunology. This review aims to provide a worked example using a clinical vignette. Furthermore, each technique is discussed in detail with its pros and cons. The index case is that of a young male with ESRD secondary to Lupus nephritis. He is offered a deceased donor kidney with a 1-0-0 mismatch. His complement dependent cytotoxicity (CDC) crossmatch reported positive for B lymphocyte, but flow cytometry crossmatch (FCXM) was reported negative for both B and T lymphocytes. Luminex-SAB (single antigen bead) did not identify any donor specific antibodies (DSA). He never had a blood transfusion. The positive CDC-crossmatch result is not concordant with DSA status. These implausible results are due to underlying lupus erythematosus, leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to Fc-receptors. False positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus, that may lead to inadvertent refusal of adequate kidney grafts. Detailed study of DSA by molecular technique would prevent wrong exclusion of such donors. Based on these investigations this patient is deemed to have "standard immunological risk" for renal transplantation.
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Affiliation(s)
- Mohammed Mahdi Althaf
- Jack Pryor Renal Unit, Norfolk and Norwich University Hospital - NHS Foundation Trust, Norwich NR4 7UY, United Kingdom
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Jon Kim Jin
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Nottingham Children Hospital, Nottingham NG7 2UH, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Mostafa Halawa
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Transplantation Surgery, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
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Konvalinka A, Tinckam K. Utility of HLA Antibody Testing in Kidney Transplantation. J Am Soc Nephrol 2015; 26:1489-502. [PMID: 25804279 DOI: 10.1681/asn.2014080837] [Citation(s) in RCA: 147] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
HLA antigens are polymorphic proteins expressed on donor kidney allograft endothelium and are critical targets for recipient immune recognition. HLA antibodies are risk factors for acute and chronic rejection and allograft loss. Solid-phase immunoassays for HLA antibody detection represent a major advance in sensitivity and specificity over cell-based methods and are widely used in organ allocation and pretransplant risk assessment. Post-transplant, development of de novo donor-specific HLA antibodies and/or increase in donor-specific antibodies from pretransplant levels are associated with adverse outcomes. Although single antigen bead assays have allowed sensitive detection of recipient HLA antibodies and their specificities, a number of interpretive considerations must be appreciated to understand test results in clinical and research contexts. This review, which is especially relevant for clinicians caring for transplant patients, discusses the technical aspects of single antigen bead assays, emphasizes their quantitative limitations, and explores the utility of HLA antibody testing in identifying and managing important pre- and post-transplant clinical outcomes.
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Affiliation(s)
| | - Kathryn Tinckam
- Department of Medicine, Division of Nephrology and Laboratory Medicine Program, HLA Laboratory, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Láng I, Taraba I, Petrányi G. Decreased antibody-dependent and spontaneous cell-mediated cytotoxicity in patients with chronic renal failure. Immunol Lett 1981; 3:267-71. [PMID: 7327620 DOI: 10.1016/0165-2478(81)90003-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Antibody-dependent and spontaneous lymphocytotoxicity of blood mononuclear cells from 15 patients with chronic renal failure was studied in allogeneic K-562 and xenogeneic chicken erythrocyte test systems. Both antibody-dependent and spontaneous cytotoxic activities were significantly decreased in uremic patients as compared to the corresponding mean values of healthy control persons and non-uremic patients with the same underlying diseases. The addition of autologous serum further reduced the impaired cytotoxic capacity of uremic lymphocytes. Uremic sera also inhibited the antibody-dependent and spontaneous lymphocytotoxicity of healthy individuals.
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Lobo PI, Spencer C, Gorman J, Pirsch G. Critical appraisal of complement dependent microlymphocytotoxicity assay for detecting donor-specific alloantibody pretransplant--importance of indirect immunofluorescence as a superior alternative. Hum Immunol 1981; 2:55-64. [PMID: 7024219 DOI: 10.1016/0198-8859(81)90007-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The ability of complement-dependent microlymphocytotoxicity assay (CdL) to detect and discriminate between the various types of donor-specific alloantibodies was reevaluated. Data obtained with the CdL assay on purified B and T lymphocytes at warm and cold temperatures was compared to other modes of antibody-detection, i.e., indirect immunofluorescence (IF) and the noncomplement-dependent antibody-dependent cellular cytotoxicity (ADCC). Additionally, the significance of antibodies as detected by CdL and IF was ascertained by correlating with kidney transplant outcome. It became apparent that the CdL assay identified weakly reactive HLA-ABC alloantibodies as being B cell specific. Such weakly reactive HLA-ABC antibodies were also not appreciated in the presence of the cold reactive IgM antibody. Accelerated rejections were the rule in the presence of weakly reactive HLA-ABC alloantibodies indicating that their detection was highly important. The IF assay could discriminate between the antibody class, could detect weakly reactive HLA-ABC alloantibodies, and could detect noncomplement fixing antibodies (ADCC). Further, use of IF prevented us from unnecessarily denying transplants to certain recipients when a positive CdL assay resulted from an IgM antibody or poor cell viability.
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Russell AS, Davis P, Miller C. Antibody dependent cell-mediated cytotoxicity to herpes simplex virus in man: the influence of drugs on polymorphonuclear leucocyte and mononuclear effector cells. PROSTAGLANDINS AND MEDICINE 1979; 3:147-58. [PMID: 233219 DOI: 10.1016/0161-4630(79)90098-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We have shown that the function of the effector cells in antibody mediated cell dependent cytotoxicity (ADCC) can be reduced by the use of a number of drugs and prostaglandins. Both polymorphonuclear leucocyte and mononuclear effector cells were studied. Aminophylline and isoproterenol markedly reduced this activity. All the prostaglandins tested--PGA1, A2, E1 and E2 had a similar but more profound effect. At a dose of 100 mg/ml hydrocortisone had relatively little influence and neither ASA nor indomethacin had any effect on the effector cells tested. It is suggested that the effect of PGE1 in stimulating a recrudescent herpes simplex infection may be by reducing the efficacy of ADCC in host defence.
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Pearson GR. In vitro and in vivo investigations on antibody-dependent cellular cytotoxicity. Curr Top Microbiol Immunol 1978; 80:65-96. [PMID: 97054 DOI: 10.1007/978-3-642-66956-9_3] [Citation(s) in RCA: 36] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Fye KH, Becker MJ, Theofilopoulos AN, Moutsopoulos H, Feldman JL, Talal N. Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay. Am J Med 1977; 62:783-91. [PMID: 16490 DOI: 10.1016/0002-9343(77)90884-1] [Citation(s) in RCA: 44] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa.
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Immunosuppression by Antibodies. Transplantation 1977. [DOI: 10.1007/978-3-642-66392-5_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Stiller CR, StC Sinclair NR, Abrahams S, McGirr D, Singh H, Howson WT, Ulan RA. Anti-donor immune responses in prediction of transplant rejection. N Engl J Med 1976; 294:978-82. [PMID: 130555 DOI: 10.1056/nejm197604292941804] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We assessed various immune responses against donor tissue to determine their value in the diagnosis and prediction of clinical rejection episodes. Twenty-six consecutive clinical renal-transplant recipients were examined. Cell-mediated lymphocytotoxicity preceded and accompanied 41 of 45 rejection episodes (P less than 0.001). Complement-dependent antibody was present in 12 of 15 rejections (P less than 0.002)--four not accompanied by, and eight in association with, cell-mediated lymphocytotoxicity. Mixed lymphocyte reactivity or nonreactivity and inhibition by autologous serum occurred equally often in rejection and quiescence. Lymphocyte-dependent antibody occurred during both rejection episodes and quiescent phases, with a greater frequency during quiescence (P = 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.001), and was more easily suppressed by standard immunosuppressive therapy, than complement-dependent antibody. If specific cell-mediated lymphocytotoxicity, with or without antibody, recurred after rejection therapy, the graft underwent further rejection.
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