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
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