Objective: The class II human leukocyte Fcy receptor for IgG (FcgammaRIIa) occurs in 2 codominantly expressed allelic forms (R131 and H131). Cells expressing IIa-H131 interact much more effectively with complexed IgG2 and IgG3 than do cells with IIa-R131. This might be linked to variability in immune complex handling, and therefore related to disease pathogenesis. The present study examines these possibilities in a cohort of Caucasian patients with systemic lupus erythematosus (SLE).
Methods: One hundred eight Caucasian patients were diagnosed with SLE according to the American College of Rheumatology criteria. The SLE patients and 187 Caucasian controls were genotyped for the FcgammaRIIa polymorphism, and associations between FcgammaRIIa genotypes, selected HLA haplotypes, and clinical as well as laboratory features were analyzed.
Results: No significant skewing of the FcgammaRIIa polymorphism was observed in the SLE cohort. Various clinical and serologic parameters were found more frequently or at a younger age in patients homozygous for the genotype IIa-R/R131 compared with those with the genotype IIa-H/H131. In patients with the genotype IIa-R/R131, significantly higher frequencies of proteinuria, hemolytic anemia, anti-nuclear RNP antibodies, and hypocomplementemia were found. The only clinical symptom observed more frequently in patients homozygous for IIa-H/H131 was livedo. Patients with the IIa-R/R131 genotype were significantly younger at disease onset and had an earlier incidence of arthritis, sicca syndrome, nephritis, lymphadenitis, hematologic abnormalities, immunologic abnormalities, lupus anticoagulant, cryoglobulinemia, and hypocomplementemia. HLA-DR3 was found in 41.7% of SLE patients, but was not associated with clinical symptoms, serologic abnormalities, or the homozygous genotypes of the FcgammaRIIa, although an association with a significantly later onset of SLE was found.
Conclusion: The FcgammaRIIa polymorphism constitutes an additional factor that might influence the clinical manifestations and course of SLE, but does not represent a genetic risk factor for the occurrence of SLE.