Evidence to Support a Contribution of Polyreactive Antibodies to HLA Serum Reactivity
| Autor: | Baoshan Gao, Fabrice Porcheray, Carolina Moore, Susan L. Saidman, Emmanuel Zorn, Chunshu Rong, Waichi Wong, Timothy C. Girouard, Yaowen Fu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Leukemia
T-Cell Genes Immunoglobulin Heavy Chain Immunoglobulin Variable Region 030232 urology & nephrology Fluorescent Antibody Technique Apoptosis Enzyme-Linked Immunosorbent Assay Human leukocyte antigen Cross Reactions 030230 surgery Biology Immunofluorescence Autoantigens Article Epitope Flow cytometry Isoantibodies Epitopes Jurkat Cells 03 medical and health sciences 0302 clinical medicine HLA Antigens medicine Humans B cell B-Lymphocytes Transplantation medicine.diagnostic_test Histocompatibility Testing Feeder Cells Flow Cytometry Kidney Transplantation Coculture Techniques Transplant Recipients Clone Cells Histocompatibility HEK293 Cells medicine.anatomical_structure Immunology biology.protein Antibody Boston |
| Zdroj: | Transplantation. 100:217-226 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/tp.0000000000000840 |
| Popis: | Background Assessing the serum reactivity to HLA is essential for the evaluation of transplant candidates and the follow-up of allograft recipients. In this study, we look for evidence at the clonal level that polyreactive antibodies cross-reactive to apoptotic cells and multiple autoantigens can also react to HLA and contribute to the overall serum reactivity. Methods We immortalized B cell clones from the blood of 2 kidney transplant recipients and characterized their reactivity to self-antigens, apoptotic cells as well as native, denatured, and cryptic HLA determinants using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, flow cytometry and Luminex assays. We also assessed the reactivity of 300 pretransplant serum specimens to HLA and apoptotic cells. Results We report here 4 distinct B cell clones cross-reactive to self and HLA class I. All 4 clones reacted to numerous HLA class I alleles but did not appear to target canonical "shared" epitopes. In parallel experiments, we observed a strong correlation between IgG reactivity to HLA and apoptotic cells in pretransplant serum samples collected from 300 kidney transplant recipients. Further analysis revealed that samples with higher reactivity to apoptotic cells displayed significantly higher class I percent panel-reactive antibodies compared to samples with low reactivity to apoptotic cells. Conclusions We provide here (1) proof of principle at the clonal level that human polyreactive antibodies can cross-react to HLA, multiple self-antigens and apoptotic cells and (2) supportive evidence that polyreactive antibodies contribute to overall HLA reactivity in the serum of patients awaiting kidney transplant. |
| Databáze: | OpenAIRE |
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