Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τετάρτη 6 Ιουνίου 2018

Therapeutic Human IgG Preparations Contain Mixture of HLA Antibodies to Native HLA Antigens and Cryptic Epitopes with Little Clinical Significance

Background Human immunoglobulins (H-Ig) are widely used in solid organ transplantation for 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 prior to testing. HLA immunoglobulin G (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 lots (73%) at 1:10 showed SAB reactivity with MFI ≥2000 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 FCXM results were positive (>150 MCS), but were 4-8 fold lower than expected. Conclusions The H-Ig products tested consisted of low titer, noncomplement binding HLA Class I and Class II antibodies; most of the observed Class I HLA reactivity was towards denatured HLA antigens. Authorship Participated in research design: Massimo Mangiola, PhD Marilyn Marrari, BA Adriana Zeevi, PhD Participated in writing the paper: Massimo Mangiola, PhD Marilyn Marrari, BA Christopher Ensor, PharmD Martin O. Spycher, PhD Mel Berger, MD Adriana Zeevi, PhD Participated in the performance of the research: Massimo Mangiola, PhD Marilyn Marrari, BA Adriana Zeevi, PhD Contributed new reagents or analytic tools: Martin O. Spycher, PhD Mel Berger, MD Participated in the data analysis: Massimo Mangiola, PhD Marilyn Marrari, BA Adriana Zeevi, PhD CONFLICT OF INTEREST DISCLOSURE: Massimo Mangiola, PhD received support from CSL Behring LLC in form of reagents and supplies to conduct research Marilyn Marrari, BA received support from CSL Behring LLC in form of reagents and supplies to conduct research Christopher Ensor, PharmD received support from CSL Behring LLC in form of reagents and supplies to conduct research Martin O. Spycher, PhD Amployed by CSL Behring AG Mel Berger, MD Amployed by CSL Behring LLC Adriana Zeevi, PhD received support from CSL Behring LLC in form of reagents and supplies to conduct research Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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