Association between -174 interleukin-6 gene polymorphism and biological response to rituximab in several systemic autoimmune diseases.
Rituximab has become a pivotal treatment for systemic autoimmune diseases. The aim of this study was to determine whether the genetic variant -174 IL-6 contributes to differences in the response to rituximab in patients with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), inflammatory myopathies, anti-neutrophil cytoplasmic antibody-mediated vasculitis, systemic sclerosis, Sjöegren's syndrome, rheumatoid arthritis, and autoimmune hemolytic anemia. DNA samples from 144 Spanish patients with different systemic autoimmune diseases receiving rituximab were genotyped for -174 IL-6 (rs1800795) gene polymorphism using the TaqMan(®) allelic discrimination technology. Six months after the first infusion with rituximab, we evaluated the response to the drug: 60.4% of the patients showed a complete response, partial 27.8%, and 11.8% did not respond to the treatment. The CC genotype frequency was significantly increased in nonresponders with respect to responders (23.5% vs. 7.1%, respectively; p=0.049; odds ratio (OR)=4.03, 95% confidence intervals (CI) 0.78-16.97). According to the genotype distribution, rituximab was effective in 69.2% of the CC carriers, 91.9% of the CG carriers, and 88.4% of the GG carriers. A similar trend was observed when SLE patients were analyzed separately (27.3% carried CC homozygosis in nonresponders and 6.9% in responders; p=0.066; OR=5.10, 95% CI 0.65-31.73). Rituximab was effective in 62.5% of the CC carriers, 88.9% of the GC carriers, and 90% of the GG carriers. These results suggest that -174 IL-6 (rs1800795) gene polymorphism plays a role in the response to rituximab in systemic autoimmune diseases. Validation of these findings in independent cohorts is warranted.
Instituto de Parasitología y Biomedicina López-Neyra-CSIC, Granada, Spain.
Gema
G
Robledo
Cristina Lucía
CL
Dávila-Fajardo
Ana
A
Márquez
Norberto
N
Ortego-Centeno
José Luis
JL
Callejas Rubio
Enrique
E
de Ramón Garrido
Julio
J
Sánchez-Román
Francisco J
FJ
García-Hernández
Raquel
R
Ríos-Fernández
Maria Francisca
MF
González-Escribano
Maria Teresa
MT
Camps García
Maria Jesús
MJ
Castillo Palma
Maria Del Mar
Mdel M
Ayala
Javier
J
Martín
D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000069283:Rituximab; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D015850:Interleukin-6; D000069283:Rituximab