Objective: To determine the role of GM and KM genes--genetic markers of immunoglobulin gamma and kappa chains, respectively--in humoral immunity to human cytomegalovirus (HCMV) in patients with systemic sclerosis (SSc; scleroderma).
Methods: A total of 137 Caucasian patients with SSc and 145 ethnically matched controls were genotyped for GM f/3, z/17, n+/23+, n-/23-, KM 1, and KM 3 alleles by polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequencing methods. IgG antibodies to HCMV were measured by an enzyme-linked immunosorbent assay.
Results: In SSc patients, GM f,z genotypes were strongly associated with the occurrence of anti-HCMV IgG antibodies. The frequency of the GM f homozygotes was lower (42.2 vs 62.2%; p= 0.02; OR=0.4) and the frequency of the GM f,z heterozygotes was higher (51.1 vs 26.7%; p = 0.006; OR = 2.8) in SSc patients with IgG antibodies to HCMV than in subjects who lacked these antibodies. This association was not observed in the control group. KM and GM n genotypes were not significantly associated with the prevalence of these antibodies.
Conclusion: GM f,z alleles or alleles in linkage disequilibrium with them influence the generation of IgG antibodies to HCMV in patients with SSc.