Polymorphism of the FcgammaRIIalpha IgG receptor in patients with lupus nephritis and glomerulopathy.
OBJECTIVE
FcgammaRIIalpha is a low affinity receptor that has 2 codominantly expressed alleles, R131 and H131, which differ in their ability to bind immunoglobulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 than those expressing the R131 variant. The FcgammaRIIalpha polymorphism has been shown to be associated with lupus nephritis. We evaluated the relevance of FcgammaRIIalpha gene polymorphism in the development of lupus immune complex mediated nephritis, as well as its clinical and histological characteristics, by comparing the genotype and allelic distribution of this receptor in lupus nephritis to ethnically matched Brazilian patients with primary glomerulonephritis.


METHODS
Patients with lupus nephritis (n = 76) and patients with diagnosis of primary glomerulonephritis (n = 63) established by kidney biopsies were recruited. FcgammaRIIalpha genotyping was performed by polymerase chain reaction with allele-specific primers to distinguish between the 2 allelic forms (H131 and R131).


RESULTS
We observed a skewed frequency of genotype FcgammaRIIalpha-R/R131 and the R131 allele in patients with lupus nephritis compared to primary glomerulopathies (p < 0.05), which disappeared when we compared this population with lupus nephritis only to the group with proliferative glomerulonephritis (IgA nephropathy, membranoproliferative glomerulonephritis, and mesangial proliferative glomerulonephritis). No association was found between genotype distribution and histological class of lupus nephritis or renal insufficiency available at the beginning and end of followup. We found an association of genotype FcgammaRIIalpha-R/R131 with higher antinuclear antigen titers and complement 3 consumption (p < 0.05).


CONCLUSIONS
The skewed distribution of FcgammaRIIalpha genotypes with the predominance of homozygous R/R131 genotype observed in patients with lupus nephritis over nonproliferative idiopathic glomerulonephritis emphasizes its importance as a heritable risk factor for immune complex mediated renal injury in Brazilian patients with lupus.
Gelmetti
Adriana Peixoto
AP
Division of Nephrology, University of São Paulo, São Paulo, Brazil. apgelmetti@terra.com.br
Freitas
Antônio Carlos
AC
Woronik
Viktoria
V
Barros
Rui Toledo
RT
Bonfá
Eloísa
E
Monteiro
Renato Costa
RC
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG