Serological blind spots for variants of human IgG3 and IgG4 by a commonly used anti-immunoglobulin reagent
| Autor: | Xiaohong Wang, Tamara C. Stegmann, Heather L. Howie, Jenna N. Lebedev, Yanyun Wu, James C. Zimring, James P. AuBuchon, Linda M. Kapp, Lay See Er, Gestur Vidarsson, Meghan Delaney |
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| Rok vydání: | 2016 |
| Předmět: |
medicine.diagnostic_test
biology Immunoglobulin Allotypes medicine.drug_class Immunology Hematology 030204 cardiovascular system & hematology Monoclonal antibody Immunoglobulin G Serology Flow cytometry 03 medical and health sciences 0302 clinical medicine Polyclonal antibodies parasitic diseases Monoclonal medicine biology.protein Immunology and Allergy Antibody 030215 immunology |
| Zdroj: | Transfusion. 56:2953-2962 |
| ISSN: | 0041-1132 |
| DOI: | 10.1111/trf.13812 |
| Popis: | BACKGROUND Human immunoglobulin G (IgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4), and it is also now appreciated that there are genetic variations within IgG subtypes (called isoallotypes). Twenty-nine different isoallotypes have been described, with 7, 4, 15, and 3 isoallotypes described for IgG1, IgG2, IgG3, and IgG4, respectively. The reactivity of anti-IgG with different isoallotypes has not been characterized. STUDY DESIGN AND METHODS A novel monoclonal anti-K antibody (PugetSound Monoclonal Antibody 1 [PUMA1]) was isolated and sequenced, and a panel of PUMA1 variants was expressed, consisting of the 29 known IgG isoallotypes. The resulting panel of antibodies was preincubated with K-positive red blood cells (RBCs) and then subjected to testing with currently approved anti-IgG by flow cytometry, solid phase systems, gel cards, and tube testing. RESULTS A US Food and Drug Administration (FDA)-approved monoclonal anti-IgG (gamma-clone) failed to recognize 2 of 15 IgG3 isoallotypes (IgG3-03 and IgG3-13) and 3 of 3 IgG4 isoallotypes (IgG4-01, IgG4-02, and IgG4-03). In contrast, an FDA-approved rabbit polyclonal anti-IgG recognized each of the known human IgG isoallotypes. CONCLUSION These findings demonstrate “blind spots” in isoalloantibody detection by a monoclonal anti-IgG. If a patient has anti-RBC antibodies predominantly of an IgG3 subtype (the IgG3-03 and/or IgG3-13 variety), then it is possible that a clinically significant alloantibody would be missed. IgG-03 and IgG-13 have an estimated frequency of 1% to 3% in Caucasian populations and 20% to 30% in certain African populations. Nonreactivity with IgG4 is a known characteristic of this monoclonal anti-IgG, but IgG4 isoallotypes have not been previously reported. |
| Databáze: | OpenAIRE |
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