Identification of IgG subclasses and C-reactive protein in lupus nephritis: the relationship between the composition of immune deposits and FCgamma receptor type IIA alleles.
OBJECTIVE
To characterize the subclass composition of IgG deposited in lupus glomeruli, to examine its relationship to allelic polymorphisms of IgG receptors (Fcgamma receptors [FcgammaR]), and to determine whether C-reactive protein (CRP), a ligand for FcgammaRIIa, is present in these immune deposits.


METHODS
Renal biopsy samples from 80 patients with lupus nephritis were examined by light microscopy and indirect immunofluorescence with IgG-subclass-specific monoclonal antibodies. FcgammaRIIA genotypes were determined using allele-specific polymerase chain reaction. Immunostaining for CRP was performed on lupus and nonlupus glomerulonephritis specimens.


RESULTS
IgG2 and IgG3 were the predominant subclasses in immune deposits in all World Health Organization classes of nephritis. The frequency of genotypes containing the low-binding IgG2 allele, FcgammaRIIa-R131, was significantly greater than expected in patients with class III or class IV nephritis and in patients with intense IgG2 deposition. CRP, a ligand with particular affinity for FcgammaRIIa-R131, was consistently present in the renal immune deposits of lupus nephritis specimens.


CONCLUSIONS
FcgammaRIIA genes are associated with proliferative renal disease and may contribute to disease pathogenesis. FcgammaRIIa-R131, the variant with low affinity for IgG2, has high affinity for CRP. Thus, FcgammaRIIa-R131 may contribute to impaired removal of circulating immune complexes, as well as efficiently triggering phagocyte activation and the release of inflammatory mediators within glomeruli.
Zuniga
Ricardo
R
Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York 10021, USA.
Markowitz
Glen S
GS
Arkachaisri
Thaschawee
T
Imperatore
Edward A
EA
D'Agati
Vivette D
VD
Salmon
Jane E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D001706:Biopsy; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics*; D012720:Severity of Illness Index
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D017452:Receptors, IgG; D002097:C-Reactive Protein