Monday, 14 April 2014

Th40 the next autoimmune subset

Waid DM, Schreiner T, Vaitaitis G, Carter JR, Corboy JR, Wagner DH Defining a new biomarker for the autoimmune component of Multiple Sclerosis: Th40 cells. J Neuroimmunol. 2014 Mar . pii: S0165-5728(14)00073-3. doi: 10.1016/j.jneuroim.2014.03.009. [Epub ahead of print]

Multiple Sclerosis (MS) is a chronic inflammatory, neurodegenerative disease. Diagnosis is very difficult requiring defined symptoms and multiple CNS imaging. A complicating issue is that almost all symptoms are not disease specific for MS. Autoimmunity is evident, yet the only immune-related diagnostic tool is cerebral-spinal fluid examination for oligoclonal bands. This study addresses the impact of Th40 cells, a pathogenic effector subset of helper T cells, in MS. MS patients including relapsing/remitting MS, secondary progressive MS and primary progressive MS were examined for Th40 cell levels in peripheral blood and, similar to our findings in autoimmune type 1 diabetes, the levels were significantly (p<0.0001) elevated compared to controls including healthy non-autoimmune subjects and another non-autoimmune chronic disease. Classically identified Tregs were at levels equivalent to non-autoimmune controls but the Th40/Treg ratio still predicted autoimmunity. The cohort displayed a wide range of HLA haplotypes including the GWAS identified predictive HLA-DRB1*1501 (DR2). However half the subjects did not carry DR2 and regardless of HLA haplotype, Th40 cells were expanded during disease. In RRMS Th40 cells demonstrated a limited TCR clonality. Mechanistically, Th40 cells demonstrated a wide array of response to CNS associated self-antigens that was dependent upon HLA haplotype. Th40 cells were predominantly memory phenotype producing IL-17 and IFN╬│ with a significant portion producing both inflammatory cytokines simultaneously suggesting an intermediary between Th1 and Th17 phenotypes.

Interleukin12 is made up of a P40 (40,000 molecular weight) and a P35 (35,000) molecular weight and interleukin23 is made up of the P40 chainof IL-12 and a P19 (19,000 molecular weight). The P40 chain is now called interleukin 40. However TH40 cells are not named after the cytokine but the expression of CD40, a co-stimulatory complex with CD154 for activation,the identification of CD4(lo)CD40(+) T cells (Th40 cells) as harboring an autoaggressive T cell population.

1 comment:

  1. Thats it the autoimune theory is dead. They keep comming up with all these new discoveries and immune cell type. Thats it. It's over. Lets focus on EBV.

    The New Nemisis


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