Multiplex serum cytokine monitoring as a prognostic tool in rheumatoid arthritis

Philip Alex, Peter Szodoray, Nicholas Knowlton, Igor M. Dozmorov, Mary Turner, Mark B. Frank, R. Eugene Arthur, Larry Willis, Don Flinn, Robert F. Hynd, Craig Carson, Ana Kumar, Hani S. El-Gabalawy, Michael Centola

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Objective: Early optimized therapy of rheumatoid arthritis (RA) results in improved outcomes. The initiation of optimized therapy is hindered by the difficulty of early diagnosis and the limitations of current disease activity and therapeutic response assessment tools. Identifying patients requiring early combination DMARD/biologic therapy is currently a significant clinical challenge given the lack of definitive prognostic criteria. Since cytokines are soluble intracellular signaling molecules that modulate disease pathology in RA, we tested the recent conjecture that en mass serum cytokine measurement and monitoring will provide a useful toolfor effective therapeutic management in PA. Methods: We assayed the levels of 16 serum cytokines in 18 RA patients treated prospectively with methotrexate and from 18 unaffected controls. Specific mechanistic aspects of inflammatory pathology in the periphery could be discerned on a patient-specific basis from patients'serum cytokine profiles, information that may aid in the design of anti-cytokine biologic therapy. A serum Cytokine Activity Index (CAI) was also created using multi-variant analysis methods. Results: Distinct cytokines were significantly elevated in RA patients relative to controls, and three distinct clusters with correlations to disease activity were identified. The Cytokine Activity Index correlated well with the therapeutic response; responders and non-responders in this cohort were distinguishable as early as one month post initiation of methotrexate therapy, well before clinical assessments of response are commonly completed. Conclusion: Clinical assessment tools could be derived from this approach that may provide a means to continually track patients, allowing intervention strategies to be better evaluated on a patient-specific basis nd to identify residual cytokine activity that could be used to guide combination therapy.

Original languageEnglish (US)
Pages (from-to)584-592
Number of pages9
JournalClinical and experimental rheumatology
Volume25
Issue number4
StatePublished - Jul 2007

Keywords

  • Cytokines
  • Rheumatoid arthritis
  • Therapeutic response

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Alex, P., Szodoray, P., Knowlton, N., Dozmorov, I. M., Turner, M., Frank, M. B., Arthur, R. E., Willis, L., Flinn, D., Hynd, R. F., Carson, C., Kumar, A., El-Gabalawy, H. S., & Centola, M. (2007). Multiplex serum cytokine monitoring as a prognostic tool in rheumatoid arthritis. Clinical and experimental rheumatology, 25(4), 584-592.