Therapeutic Human IgG Preparations Contain Mixture of HLA Antibodies to Native HLA Antigens and Cryptic Epitopes With Little Clinical Significance
| Autor: | Marilyn Marrari, Christopher R. Ensor, Adriana Zeevi, Massimo Mangiola, Martin O. Spycher, M. Berger |
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| Rok vydání: | 2018 |
| Předmět: |
Protein Denaturation
Human leukocyte antigen Histocompatibility Testing Cross Reactions 030204 cardiovascular system & hematology 030230 surgery Risk Assessment Epitope Immunoglobulin G Flow cytometry Epitopes 03 medical and health sciences 0302 clinical medicine HLA Antigens Isoantibodies medicine Humans Immunologic Factors Transplantation biology medicine.diagnostic_test business.industry Histocompatibility Titer Immunology biology.protein Antibody business |
| Zdroj: | Transplantation. 102:2126-2132 |
| ISSN: | 1534-6080 0041-1337 |
| DOI: | 10.1097/tp.0000000000002312 |
| Popis: | Background Human immunoglobulins (H-Ig) are widely used in solid organ transplantation for immunoglobulin G (IgG) replacement and for desensitization and treatment of antibody-mediated rejection. They are obtained from plasma pools and may contain HLA antibodies that can be detrimental to transplant recipients. The goal of this study was to evaluate HLA antibodies in multiple lots of 2 commercial H-Ig preparations by Luminex single-antigen bead (SAB) and cell-based crossmatch assays. Methods Thirty lots of 2 commercial H-Ig products (CSL Behring, King of Prussia, PA) were evaluated: 6 Hizentra and 24 Privigen. All were adsorbed and diluted 1:10 before testing. HLA IgG antibodies were determined by 2 Luminex SAB kits and C1q screen for complement-binding capability. Lots were tested for the presence of antibody to denatured vs. intact class I HLA alleles using acid-treated SAB. Surrogate T and B-cell flow cytometry crossmatches (FCXM) were performed with peripheral blood lymphocytes from 2 healthy donors. Results Twenty-two (73%) lots at 1:10 showed SAB reactivity with mean fluorescent intensity of 2000 or greater for HLA class I, 67% (20/30 lots) for class II. The reactivity pattern was similar using both SAB kits. Acid treatment revealed antibodies to denatured class I: the majority of HLA-C, half of HLA-B and few HLA-A alleles. No C1q reactivity was observed. Surrogate flow cytometry crossmatch results were positive (>150 median channel shift), but were fourfold to eightfold lower than expected. Conclusions The H-Ig products tested consisted of low titer, non-complement-binding HLA class I and class II antibodies; most of the observed class I HLA reactivity was toward denatured HLA antigens. |
| Databáze: | OpenAIRE |
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