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New Findings from University of Michigan in Rheumatoid Arthritis Provides New Insights (Synovial phenotypes in rheumatoid arthritis correlate with...

August 20, 2014

New Findings from University of Michigan in Rheumatoid Arthritis Provides New Insights (Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics)

By a News Reporter-Staff News Editor at Biotech Week -- New research on Autoimmune Diseases is the subject of a report. According to news reporting originating from Ann Arbor, Michigan, by NewsRx correspondents, research stated, "Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood."

Our news editors obtained a quote from the research from the University of Michigan, "We analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts. To identify candidate serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies, we performed pre treatment biomarker analysis compared with therapeutic outcome at week 24 in serum samples from 198 patients from the ADACTA (ADalimumab ACTemrA) phase 4 trial of tocilizumab (anti-IL-6R) monotherapy versus adalimumab (anti-TNF alpha) monotherapy. We documented evidence for four major phenotypes of RA synovium -lymphoid, myeloid, low inflammatory, and fibroid - each with distinct underlying gene expression signatures. We observed that baseline synovial myeloid, but not lymphoid, gene signature expression was higher in patients with good compared with poor European league against rheumatism (EULAR) clinical response to anti-TNFa therapy at week 16 (P = 0.011). We observed that high baseline serum soluble intercellular adhesion molecule 1 (sICAM1), associated with the myeloid phenotype, and high serum C-X-C motif chemokine 13 (CXCL13), associated with the lymphoid phenotype, had differential relationships with clinical response to anti-TNFa compared with anti-IL6R treatment. sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology (ACR) 50 response rate to anti-TNFa treatment as compared with sICAM1-low/CXCL13-high patients (42% versus 13%, respectively, P = 0.05) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups (ACR50 20% versus 69%, P = 0.004). /Conclusions: These data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways, with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFa."

According to the news editors, the research concluded: "These data suggest a path to identify and validate serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases."

For more information on this research see: Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Research & Therapy, 2014;16(2):415-432. Arthritis Research & Therapy can be contacted at: Biomed Central Ltd, 236 Grays Inn Rd, Floor 6, London WC1X 8HL, England. (BioMed Central -; Arthritis Research & Therapy -

The news editors report that additional information may be obtained by contacting G. Dennis, University of Michigan, Sch Med, Dept. of Internal Med, Div Rheumatol, Ann Arbor, MI, United States. Additional authors for this research include C.T.J. Holweg, S.K. Kummerfeld, D.F. Choy, A.F. Setiadi, J.A. Hackney, P.M. Haverty, H. Gilbert, W.Y. Lin, L. Diehl, S. Fischer, A. Song, D. Musselman, M. Klearman, C. Gabay, A. Kavanaugh, J. Endres, D.A. Fox, F. Martin and Tow (see also Autoimmune Diseases).

Keywords for this news article include: Pharmaceuticals, Therapy, Michigan, Peptides, Proteins, Ann Arbor, Cytokines, United States, CXC Chemokines, Joint Diseases, Chemokine CXCL13, Biological Factors, Autoimmune Diseases, Rheumatoid Arthritis, Musculoskeletal Diseases, North and Central America

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC

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Source: Biotech Week

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