Up-regulated MHC-class II expression and γ-IFN and soluble IL-2R in lupus nephritis

Up-regulated MHC-class II expression and γ-IFN and soluble IL-2R in lupus nephritis. Expression of MHC-class II molecules (HLA-DR and -DQ), serum gamma-interferon (γ-IFN) and soluble interleukin-2 receptor (sIL-2R) levels were studied in 35 Japanese patients with lupus nephritis (LN) to clarify intraglomerular cellular activation and cytokine involvement in human LN. In 11 normal kidney specimens, HLA-DR(Ial) was noted in glomerular tufts, but HLA-DQ was either not or was faintly detected in glomeruli by the indirect immunofluorescence technique. HLA-DR and -DQ were observed mainly on the surface of glomerular endothelial cells in 100% and 50% of 28 lupus kidney specimens except for necrotic or sclerotic lesions. HLA-DQ was expressed in a high incidence of 67%, 86% in patients with proliferative LN (WHO Class III-IV) and active lesions, respectively. Serum γ-IFN and sIL-2R levels were 1.2 ± 0.2 U/ml and 190 ± 24 U/ml (mean ± SEM; N = 30) in normal controls, and elevated in patients with proliferative LN (4.1 ± 1.0 U/ml, 383 ± 81 U/ml, N = 25), especially with active lesions (6.2 ± 1.5 U/ml, 500 ± 110 U/ml, N = 14). Overall, glomerular lesions such as HLA-DQ expression, the activity index and leukocyte infiltration correlated positively with serum γ-IFN levels (r = 0.55; P < 0.01 for HLA-DQ, r = 0.68; P < 0.001 for activity index, r = 0.38; P < 0.05 for leukocyte infiltration), but not with serum sIL-2R levels, anti-DNA antibody titers and CH50 titers. The aberrant expression of HLA-DQ in glomeruli was significantly reduced by treatment with methylprednisolone pulse therapy, concomitant with normalization of serum γ-IFN and sIL-2R levels. We conclude that the aberrant expression of MHC-class II molecules in glomeruli and serum γ-IFN concentrations are related to the proliferative and active lesions including leukocyte infiltration of human LN, and these abnormalities in vivo are improved by methylprednisolone pulse therapy. These results suggest that MHC-class II molecules and γ-IFN may play an important role in the tissue injury of human LN