Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura
BackgroundThe acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying deficiency of the ADAMTS13 protease is caused by autoantibodies, predominantly of the IgG isotype. Certain HLA-DR-DQ haplotypes were associated with the risk of devel...
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01646/full |
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| author | György Sinkovits Ágnes Szilágyi Péter Farkas Dóra Inotai Anikó Szilvási Attila Tordai Katalin Rázsó Marienn Réti Zoltán Prohászka |
| author_facet | György Sinkovits Ágnes Szilágyi Péter Farkas Dóra Inotai Anikó Szilvási Attila Tordai Katalin Rázsó Marienn Réti Zoltán Prohászka |
| author_sort | György Sinkovits |
| collection | DOAJ |
| description | BackgroundThe acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying deficiency of the ADAMTS13 protease is caused by autoantibodies, predominantly of the IgG isotype. Certain HLA-DR-DQ haplotypes were associated with the risk of developing TTP.ObjectivesTo investigate the development of the ADAMTS13-specific antibody response during the course of the disease, we analyzed the concentration, subclass distribution, and inhibitory potential of anti-ADAMTS13 IgG autoantibodies in samples of TTP patients drawn during the first acute phase, in remission, and during relapse. Additionally, we compared the anti-ADAMTS13 IgG levels between patients carrying and not carrying risk and protective HLA-DR-DQ haplotypes.Patients and MethodsWe determined the anti-ADAMTS13 IgG concentration and subclass distribution in 101 antibody-positive samples of 81 acquired TTP patients by ELISA methods. The presence and semi-quantitative amount of anti-ADAMTS13 inhibitors were determined in 97 of 100 deficient samples, and the specific inhibitory potential of anti-ADAMTS13 autoantibodies was determined in 49 selected samples, by mixing ADAMTS13-activity assays. HLA-DR-DQ typing and haplotype prediction were performed in 70 of the above patients.ResultsWe found that IgG1 and IgG4 were the predominant subclasses, present in almost all samples. While IgG1 was the dominant subclass in almost half of the samples taken during the first acute episode, IgG4 was dominant in all samples taken during or following a relapse. The inhibitory potential of the samples correlated with levels of the IgG4 subclass. Anti-ADAMTS13 antibodies of IgG4-dominant samples had higher specific inhibitory potentials than IgG1-dominant samples, independently of disease stage. Interestingly, we found that patients carrying the protective DR7-DQ2 and DR13-DQ6 haplotypes had higher anti-ADAMTS13 IgG levels.ConclusionOur results indicate that IgG4 becomes the dominant subtype at some point of the disease course, apparently before the first relapse, parallel to the increase in inhibitory potential of the anti-ADAMTS13 autoantibodies. Furthermore, we found an association between the genetic background and the antibody response in TTP. |
| first_indexed | 2024-12-21T04:06:08Z |
| format | Article |
| id | doaj.art-aba693e6313e429fbea205b631df491a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T04:06:08Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aba693e6313e429fbea205b631df491a2022-12-21T19:16:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01646384666Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic PurpuraGyörgy Sinkovits0Ágnes Szilágyi1Péter Farkas2Dóra Inotai3Anikó Szilvási4Attila Tordai5Katalin Rázsó6Marienn Réti7Zoltán Prohászka8Research Laboratory, 3rd Department of Internal Medicine and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryResearch Laboratory, 3rd Department of Internal Medicine and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary3rd Department of Internal Medicine, Semmelweis University, Budapest, HungaryLaboratory of Transplantation Immunogenetics, Hungarian National Blood Transfusion Service, Budapest, HungaryLaboratory of Transplantation Immunogenetics, Hungarian National Blood Transfusion Service, Budapest, HungaryDepartment of Pathophysiology, Semmelweis University, Budapest, HungaryDivision of Haematology, Deptartment of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDepartment of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute of Haematology and Infectious Diseases, Budapest, HungaryResearch Laboratory, 3rd Department of Internal Medicine and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryBackgroundThe acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying deficiency of the ADAMTS13 protease is caused by autoantibodies, predominantly of the IgG isotype. Certain HLA-DR-DQ haplotypes were associated with the risk of developing TTP.ObjectivesTo investigate the development of the ADAMTS13-specific antibody response during the course of the disease, we analyzed the concentration, subclass distribution, and inhibitory potential of anti-ADAMTS13 IgG autoantibodies in samples of TTP patients drawn during the first acute phase, in remission, and during relapse. Additionally, we compared the anti-ADAMTS13 IgG levels between patients carrying and not carrying risk and protective HLA-DR-DQ haplotypes.Patients and MethodsWe determined the anti-ADAMTS13 IgG concentration and subclass distribution in 101 antibody-positive samples of 81 acquired TTP patients by ELISA methods. The presence and semi-quantitative amount of anti-ADAMTS13 inhibitors were determined in 97 of 100 deficient samples, and the specific inhibitory potential of anti-ADAMTS13 autoantibodies was determined in 49 selected samples, by mixing ADAMTS13-activity assays. HLA-DR-DQ typing and haplotype prediction were performed in 70 of the above patients.ResultsWe found that IgG1 and IgG4 were the predominant subclasses, present in almost all samples. While IgG1 was the dominant subclass in almost half of the samples taken during the first acute episode, IgG4 was dominant in all samples taken during or following a relapse. The inhibitory potential of the samples correlated with levels of the IgG4 subclass. Anti-ADAMTS13 antibodies of IgG4-dominant samples had higher specific inhibitory potentials than IgG1-dominant samples, independently of disease stage. Interestingly, we found that patients carrying the protective DR7-DQ2 and DR13-DQ6 haplotypes had higher anti-ADAMTS13 IgG levels.ConclusionOur results indicate that IgG4 becomes the dominant subtype at some point of the disease course, apparently before the first relapse, parallel to the increase in inhibitory potential of the anti-ADAMTS13 autoantibodies. Furthermore, we found an association between the genetic background and the antibody response in TTP.https://www.frontiersin.org/article/10.3389/fimmu.2018.01646/fullthrombotic thrombocytopenic purpuraanti-ADAMTS13 autoantibodiesIgG subclassesADAMTS13-inhibitorsHLA-DRB1-DQB1 haplotypes |
| spellingShingle | György Sinkovits Ágnes Szilágyi Péter Farkas Dóra Inotai Anikó Szilvási Attila Tordai Katalin Rázsó Marienn Réti Zoltán Prohászka Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura Frontiers in Immunology thrombotic thrombocytopenic purpura anti-ADAMTS13 autoantibodies IgG subclasses ADAMTS13-inhibitors HLA-DRB1-DQB1 haplotypes |
| title | Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura |
| title_full | Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura |
| title_fullStr | Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura |
| title_full_unstemmed | Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura |
| title_short | Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura |
| title_sort | concentration and subclass distribution of anti adamts13 igg autoantibodies in different stages of acquired idiopathic thrombotic thrombocytopenic purpura |
| topic | thrombotic thrombocytopenic purpura anti-ADAMTS13 autoantibodies IgG subclasses ADAMTS13-inhibitors HLA-DRB1-DQB1 haplotypes |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01646/full |
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