Anti-IL21 monoclonal antibody, clone TC245g

A recent study in the nonobese diabetic (NOD) mouse demonstrated the involvement of interleukin (IL)-21 in the pathogenesis of type 1 diabetes. A strong susceptibility locus, Idd3, has also been mapped to the interval containing the routine gene for IL-21 (I/21), making I/21 and the human orthologue IL21 a functional and positional candidate gene for type 1 diabetes. To investigate the contribution of the human genes for IL-21 and its receptor (IL-21R) to susceptibility to type 1 diabetes, we re-sequenced IL21 to identify novel sequence variants, searched for informative variants of IL21R, and studied the association of theme variants with the disease. Two polymorphisms, a single nucleotide polymorphism (SNP) and a mononucleotide repeat polymorphism, were identified for IL21, and an allele of the mononucleotide repeat polymorphism was positively associated with the IL21R were identified, one of which was associated with the disease. Scoring of individuals according to the status of these alleles showed a significant trend for high scores for susceptibility in diabetes patients, suggesting the contribution of IL21 and IL21R to disease susceptibility in an additive manner. These data suggest a contribution of IL21 and IL21R to genetic susceptibility to type 1 diabetes and possible involvement of IL-21 and its receptor system in the disease pathogenesis.

Isolated IgG4 tubulointerstitial nephritis (TIN) is a rare disorder characterized by raised serum IgG4 levels and histological findings of dense lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells. We report a case of isolated IgG4 TIN that presented with acute kidney injury in an 84 year old man with a polyclonal increase in his total IgG and a raised IgE of 381 kUA/L but without evidence of systemic autoimmunity. We draw a parallel with IgG4-related autoimmune pancreatitis and show raised levels of circulating regulatory T cells. Importantly the plasma levels of the T regulatory cell cytokine, IL10, the TH1 cytokines IL12 and IFN gamma, the proinflammatory TNF alpha and immune regulatory IL27 were all highly raised. Furthermore, the level of IL21 that promotes IgG4 production was also very significantly elevated. These results suggest efforts of the immune system to reduce inflammation and suppress an exaggerated Th2 response. A raised serum IgG in the setting of acute kidney injury and in the absence of autoimmunity and chronic infection should encourage an assessment of the IgG subclasses. Prompt steroid treatment of those with a raised IgG4 may reduce ongoing renal damage.