Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab
Autor: | Bengt Fadeel, Inger Vedin, Jan Palmblad, Hans Hägglund, Daniel Tesfa, Sofia Ajeganova, Anna Linda Zignego |
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Přispěvatelé: | Rheumatology |
Rok vydání: | 2017 |
Předmět: |
Male
Receptors IgG/genetics Late-onset neutropenia Rheumatic Diseases/drug therapy 0302 clinical medicine Neutropenia/chemically induced Rituximab/adverse effects Genotype Medicine(all) Genetic Predisposition to Disease/genetics FCGR3A Middle Aged Antirheumatic Agents 030220 oncology & carcinogenesis young adult BAFF Female Rituximab Research Article medicine.drug Adult medicine.medical_specialty Neutropenia Adolescent FCGR Case-control studies FCGR2B FCGR2A Antirheumatic Agents/adverse effects Polymorphism Single Nucleotide 03 medical and health sciences Rheumatic Diseases Internal medicine medicine Humans Genetic Predisposition to Disease Polymorphism B-cell activating factor Aged Retrospective Studies Rheumatology and Autoimmunity 030203 arthritis & rheumatology Reumatologi och inflammation business.industry Receptors IgG medicine.disease Rheumatology Immunology bacteria Rheumatic disease aged 80 and over business |
Zdroj: | Arthritis Research & Therapy |
ISSN: | 1478-6362 |
Popis: | Background: The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fc gamma receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. Methods: A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism -871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and polymorphisms. Results: The FCGR3A V allele, but not other FCGR polymorphisms, correlated with the occurrence of LON; each V allele conferred a fourfold increased OR for LON (p = 0.017). FCGR3A 158V/V and presentation with LON were associated with a longer flare-free survival (p = 0.023 and p = 0.031, respectively). FCGR3A 158V/V was related to lower IgM levels (p = 0.016). Serum BAFF levels showed no relationship with LON and BAFF -871C/T promoter polymorphism. There was a tendency toward longer flare-free survival in patients with the BAFF -871T/T allotype compared with the C/T or C/C allotypes (p = 0.096). Conclusions: The results of the present study suggest that presentation with LON may be a result of the intrinsic efficacy of rituximab in patients with rheumatic diseases. LON could indicate a longer biological and therapeutic activity of rituximab modulated by a certain genotypic polymorphism: the high-affinity FCGR3A V allele. This genotype and the occurrence of LON are both related to longer flare-free survival, suggestive of common mechanisms for LON and duration of response to rituximab. The role of the BAFF -871C/T promoter polymorphism in LON occurrence is unclear. |
Databáze: | OpenAIRE |
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