75 FcgRIIa polymorphisms are associated with lupus nephritis in mexican patients

Abstract

BackgroundSystemic Lupus erythematosus (SLE) is an autoimmune disease mediated by the deposit of immune complexes of autoantibodies which are potentially inflammatory since they can activate the innate immune response through binding to FcgR. The SLE prevalence is 80 per 1 00 000 inhabitants, this prevalence is similar in other population groups, however, the presence of Lupus Nephritis is particularly high in Mexicans (60% of renal disease compared to 12% in Caucasian population), this data is relevant since the diversity of susceptibility genes that have been identified in Mexican patients are from Caucasian origin, despite this the lupus phenotype in Mexican Mestizo is different to any other population. The most important thing to consider is the impact that lupus nephritis causes in health status and quality of life of patients. In this study, the aim was to investigate whether the distribution of the FcgRIIa polymorphisms determines susceptibility to lupus nephritis, the main clinical manifestation in mestizo Mexican patient.MethodsA total of 111 patients that fulfilled the American College of Rheumatology (ACR) classification criteria for SLE and 102 healthy volunteers have been included in this study.FCGR2A genotypes were determined by polymerase chain reaction-based allotyping methods with allele-specific probes; the clinical features were obtained from patients official medical records.ResultsAbout polymorphism, when different groups of patients were compared: SLE with and without renal activity (defined as ACR criteria) there were found statistical differences between the groups, the genotype RR-131 (p=0.04, OR=3.61) was increased in patients with renal activity or history of this clinical manifestation. Additionally, it was found that the patients classified by biopsy with proliferative membrane glomerulonephritis, were mostly the patients with the GG genotype (60%).Abstract 75 Table 1FcgIIa genotypes in SLE patients. LEG +act renal LEG sin act. Renal n=77 n=34 pC OR IC95% Genotipos n (frecuencia) n (frecuencia) R131/R13125 (0.32)4 (0.12) 0.04 3.61 1.15–11.35 R131/H13141 (0.53)19 (0.56)NSH131/H13111 (0.15)11 (0.32) 0.05 0.35 0.13–0.91 Comparison of FcgIIa genotypes among patients who have presented renal activity compared with patients who have not presented renal activity.ConclusionsThe results demonstrate that FcgRIIa polymorphism is associated with susceptibility to lupus nephritis in Mexican patients. The hypothesis for this association could be related to the role of this receptor in the clearance of immune complexes, mainly by innate immune cells like neutrophils which have been identified in biopsies of these patients. Additionally, the activation of this receptor by the engage with immune complexes activate different immune lineage cells which function is affected by the presence of polymorphisms. Functional studies are necessary to determine how this polymorphism affects the effector activity of these cells and the consequences in renal tissue.Funding Source(s)...