Human Proteinase-3 IgG ELISA Kit

Lupus nephritis is a chronic autoimmune-inflammatory condition that can lead to end-stage kidney disease. Presently available immunosuppressive treatments for lupus nephritis are suboptimal and can induce significant side effects. Recently, we characterized a novel immunomodulatory activity of the minor isoform of the classical pathway complement inhibitor, C4BP(beta-). We show here that C4BP(beta-) treatment prevented the development of proteinuria and albuminuria, decreased significantly the formation of anti-dsDNA antibodies and, locally, mitigated renal glomerular IgG and C3 deposition and generation of apoptotic cells. There was a consequent histological improvement and increased survival in lupus-prone mice. The therapeutic efficacy of C4BP(beta-) was analogous to that of the broad-acting immunosuppressant cyclophosphamide. Remarkably, a comparative transcriptional profiling analysis revealed that the kidney gene expression signature resulting from C4BP(beta-) treatment turned out to be 10 times smaller than that induced by cyclophosphamide treatment. C4BP(beta-) immunomodulation induced significant downregulation of transcripts relevant to lupus nephritis indicating immunopathogenic cell infiltration, including activated T cells (Lat), B cells (Cd19, Ms4a1, Tnfrsf13c), inflammatory phagocytes (Irf7) and neutrophils (Prtn3, S100a8, S100a9). Furthermore, cytokine profiling and immunohistochemistry confirmed that C4BP(beta-), through systemic and local CXCL13 downregulation, was able to prevent ectopic lymphoid structures neogenesis in aged mice with lupus nephritis. Thus, due to its anti-inflammatory and immunomodulatory activities and high specificity, C4BP(beta-) could be considered for further clinical development in patients with systemic lupus erythematosus.

Wegener's granulomatosis is an autoimmune disease with unique characteristics. The formation of anti-neutrophil cytoplasmic autoantibodies (ANCAs) is closely correlated with disease activity and is highly specific for this disease. The obligate target antigen, proteinase 3 (gene symbol, PRTN3), is located in peroxidase-positive granules of neutrophils and certain monocytes, minor amounts of the autoantigen are also associated with the surface membrane of unprimed neutrophils. Cloning and sequencing of the PRTN3 gene revealed closest similarity to neutrophil elastase (gene symbol, ELA2), and azurocidin (AZU1) which are serine protease holomogs involved in immune defense reactions. The genes encoding AZU1, PRTN3 and ELA2 are closely clustered within a genomic distance of 50 kb on the short arm of human chromosome 19 (19p13.3) and have the same transcriptional orientation. Granzym M, a granule-associated serine protease of killer cells implicated in target cell killing is located 300 kb from this locus towards the telomer, and shares the same exon-intron organization as the three neutrophil elastase homologs. Two additional multigene loci encoding highly related serine proteases of haematopoietic cell lineages have previously been identified on human chromosome 14q11.2 and 5q11-12. Future investigations will clarify whether allelic variations in these serine protease loci are correlated with an increased susceptibility for Wegener's granulomatosis, chronic obstructive pulmonary disease, and other forms of chronic tissue injury.