HLA-Gm/kappa m interaction in sarcoidosis. Suggestions for a complex genetic structure

The aetiology of sarcoidosis is still unknown, Environmental exposures are believed to interact with genetic factors in determining the pattern of sar coidosis presentation, progression and prognosis. The frequency of serological polymorphism of immunoglobulin G heavy chain ( Gm) and kappa light chain (kappa m) markers in 107 patients with biopsy-pro ven sarcoidosis and in 227 controls, and their interactions with histocompa tibility leukocyte antigen (HLA) class I, II, and III markers, were studied . A "protective" effect of the Gm(3 5*) phenotype in the sarcoid group versus controls (p-value for number of specificities tested (pc)=0.05, odds ratio 0.15) and a reduced frequency of Gm(3 23 5*) in patients with advanced che st radiographic stage (Chi-squared two degrees of freedom)(chi(2)(2dr) 17.6 1, pc=0.0058) were observed. With reference to epistatic interactions, the combination Cm(3 23 5*)/BfS had a "protective" effect towards stage II (chi (2)(2dr) 13.86, pc=0.043), Finally, correspondence analysis defined two clu sters: HLA-DR4, C4BQ0, Gm(1, 3, 17 23 5*, 21, 28) and BfF associated with s tage II, and HLA-DR3, C4AQ0, kappa m(1) and Gm(3 23 5*) associated with sta ge I. These data further support the hypothesis that sarcoidosis results from an interplay of environmental factors and genes, each contributing to the susc eptibility/resistance to and/or the clinical heterogeneity of the disease, In addition, these data provide the first evidence of an interaction betwee n immunoglobulin G heavy chain/kappa light chain markers and histocompatibi lity leukocyte antigen class III genes in a disease.