Identification of IgG subclasses and C‐reactive protein in lupus nephritis: The relationship between the composition of immune deposits and FCγ receptor type IIA alleles

Abstract Objective To characterize the subclass composition of IgG deposited in lupus glomeruli, to examine its relationship to allelic polymorphisms of IgG receptors (Fcγ receptors [FcγR]), and to determine whether C‐reactive protein (CRP), a ligand for FcγRIIa, 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. FcγRIIA 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, FcγRIIa‐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 FcγRIIa‐R131, was consistently present in the renal immune deposits of lupus nephritis specimens. Conclusion FcγRIIA genes are associated with proliferative renal disease and may contribute to disease pathogenesis. FcγRIIa‐R131, the variant with low affinity for IgG2, has high affinity for CRP. Thus, FcγRIIa‐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.