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

Abstract

Expression of MHC-class II molecules (HLA-DR and -DQ), serum gamma-interferon (gamma-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(Ia1) 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 gamma-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 gamma-IFN levels (r = 0.55; P less than 0.01 for HLA-DQ, r = 0.68; P less than 0.001 for activity index, r = 0.38; P less than 0.05 for leukocyte infiltration), but not with serum sIL-2R levels, anti-DNA antibody titers and CH50 titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Atorvastatin Inhibits Autoreactive B Cell Activation and Delays Lupus Development in New Zealand Black/White F1 Mice

“…Glomerular MHC-II expression is increased in lupus patients, and this increase correlated with disease activity, whereas prednisolone therapy reduced MHC-II expression (10), suggesting that targeting glomerular MHC-II expression may be a useful approach in lupus patients. There are a number of other possible mechanisms by which atorvastatin might reduce glomerular injury, including a reduction in cellular proliferation via modulation of the Rho GTPase signaling pathway (23) and a reduction in trafficking of macrophages and lymphocytes to the glomerulus (4,24).…”

Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis

“…13 IFN-γ or molecules that are upregulated by IFN-γ, such as IFN-γ-inducible protein 10 (CXCL-10), human leukocyte antigen (HLA) class II and neopterin, are present at increased levels in patients with SLE, including those with LN, and have been associated with disease activity and flares. [14][15][16][17][18][19][20] AMG 811 is a fully human (IgG1) anti-IFN-γ antibody. In patients with mild-to-moderate SLE, single doses of AMG 811 normalised IFN-regulated gene expression, led to dose-related reductions in serum CXCL-10, and were well tolerated.…”

Single nucleotide polymorphisms in the gene encoding the major histocompatibility complex class II transactivator (CIITA) in systemic lupus erythematosus

“…It has been reported that MHC class II antigen expression is enhanced in lupus nephritis in humans and in mice models. [5][6][7] Therefore a particular allele of the polymorphic gene which plays a part in the regulation of MHC class II expression might be involved in the predisposition to SLE. In this report, we examine the association between SNPs in the human CIITA gene, MHC2TA, and SLE.…”