Interplay of immunoglobulin G heavy chain markers (Gm) and HLA in predisposing to systemic lupus nephritis.

We have studied the distribution of IgG heavy chain markers (Gm) among 90 Hungarian patients with systemic lupus erythematosus (SLE) (55 of whom were also typed for HLA). This study confirms previously described increases in HLA-B8 and DR3 in this condition. No difference in the distribution of Gm phenotypes was found between patients and 168 controls from the same geographical area. HLA-B8/Gm homozygous individuals were, however, at greater risk for SLE (relative risk = 5.13) compared to B8 + Gm heterozygotes or B8- individuals, irrespective of Gm phenotype. When patients with renal manifestation (n = 40) were compared to those without, the Gm phenotype 3; 5, 13 was found to be significantly increased (chi 2 = 10.36, P less than 0.0001, relative risk (RR) = 4.69). HLA and Gm increased additively the risk for renal manifestations in that for those patients who were both Gm3;5,13+ and HLA-B8+, PR was 110, while it was 21.2 for Gm3;5, 13-/B8+, 7.9 for Gm3;5, 13+/B8- and 1.0 for Gm3;5, 13-/B8- patients. The study suggests that combined HLA and Gm typing can be used to identify SLE patients at high risk for manifesting renal abnormalities.