Mouse Anti human RORC monoclonal antibody, clone 5H520

Objectives: To assess potential roles of effector cells and immunologic markers in demyelinating CNS lesion formation, and their modulation by interferon beta-1 alpha (IFN-beta-1 alpha). Methods: Twenty-three patients with relapsing-remitting multiple sclerosis (RRMS) received IFN-beta-1 alpha for 6 months. Immunologic marker results were correlated with brain MRI lesion volumes, and volumes of normal-appearing brain tissue (NABT) with decreasing or increasing voxel-wise magnetization transfer ratio (VW-MTR), suggestive of demyelination and remyelination, respectively. Results: Baseline expression of Th22 cell transcription factor aryl hydrocarbon receptor (AHR) and interleukin (IL)-17F, and percentages of IL-22-expressing CD4(+) and CD8(+) cells, were significantly higher in patients vs 15 healthy controls; IL-4 in CD4(+) cells was lower. Baseline percentage of IL-22-producing CD8(+) cells positively correlated with T2 lesion volumes, while percentage of IL-17A-producing CD8(+) cells positively correlated with T2 and T1 lesion volumes. IFN-beta-1 alpha induced reductions in transcription factor AHR, T-bet, and retinoic acid-related orphan nuclear hormone receptor C (RORc) gene expression, while it increased GATA3's expression in CD41 cells. Percentages of IL-22-, IL-17A-, and IL-17F-expressing T cells significantly decreased following treatment. Increased percentages of IL-10-expressing CD4(+) and CD8(+) cells correlated with greater NABT volume with increasing VW-MTR, while decreased percentage of IL-17F-expressing CD4(+) cells positively correlated with decreased NABT volume with decreasing VW-MTR. Conclusions: Findings indicate that IFN-beta-1 alpha suppresses Th22 and Th17 cell responses, which were associated with decreased MRI-detectable demyelination. Classification of evidence: This pilot study provides Class III evidence that reduced Th22 and Th17 responses are associated with decreased demyelination following IFN-beta-1 alpha treatment in patients with RRMS.

T-helper (Th) 22 and Th17 cells are implicated in the pathogenesis of autoimmune diseases. However, the role of Th22 cells in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Th22, Th17 and Th1 cells in both ITP patients and healthy controls were examined by flow cytometry. Plasma interleukin-22 (IL-22) level was measured by enzyme linked immunosorbent assay (ELISA). Signal transducers and activators of transcription 3 (STAT-3) and transcription factor RAR-related organ receptor C (RORC) messenger RNA (mRNA) expressions were examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Th22 cells, Th17 cells, Th1 cells and plasma 11-22 were significantly higher in ITP patients than in healthy controls. Moreover, Th22 cells showed a positive correlation with the levels of plasma IL-22 as well as Th17 and Th1 cells in ITP patients. Significant up-regulations of both STAT-3 and RORC transcription factors were also observed. Additionally, the percentage of Th22 cells was higher in autoantibody-negative ITP patients than in autoantibody-positive patients. Our results demonstrate a possible role of Th22 cells in ITP, and thus, the blockade of IL-22 may be a reasonable therapeutic strategy for ITP. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.