ORIGINAL ARTICLE Identification of acute phase reactants and cytokines useful for monitoring infliximab therapy in ankylosing spondylitis Consuelo Romero-Sánchez & William H. Robinson & Beren H. Tomooka & John Londoño & Rafael Valle-Oñate & Feng Huang & Xiaohu Deng & Liyun Zhang & Chunhua Yang & David Tak Yan Yu Received: 10 March 2008 / Revised: 13 May 2008 / Accepted: 14 May 2008 / Published online: 20 June 2008 # Clinical Rheumatology 2008 Abstract Although most ankylosing spondylitis patients show an apparent clinical response to infliximab therapy, there is considerable individual variation. Because current clinical assessment relies heavily on subjective patient self- evaluation, biomarkers of high sensitivity and specificity are much needed. Here, we assessed potential biomarkers in 47 ankylosing spondylitis patients who received three standard pulses of infliximab. Before each infusion and at week 10, the following were measured: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count, serum levels of metalloproteinase-3 (MMP-3), and 22 different cytokines. We discovered that, 2 weeks after the first infusion, the combination of ESR, CRP, and platelet count distinguished responders from non-responders with 81.3% sensitivity and 72.7% specificity. The distin- guishing power was much less when each acute phase reactant was used alone. Among the 22 cytokines, serum IL- 1α was able to distinguish responders from non-responders at week 6, with sensitivity of 84.9% and specificity of 53.8%. Serum IL-1α was probably generated from the joint compartments, as synovial fluid levels were much higher than corresponding serum levels. Although infliximab infusions led to rapid and significant suppression of serum MMP-3 levels, serum MMP-3 levels did not distinguish responders from non-responders. Besides identifying poten- tial biomarkers, our results also demonstrate the usefulness of using sensitivity and specificity to assess usefulness of potential biomarkers. Keywords Ankylosing spondylitis . Biomarkers . Infliximab Ankylosing spondylitis (AS), a major member of the spondyloarthritis (SpA) family, is characterized by inflam- matory spinal pain and occasionally by peripheral joint and entheses swelling [1]. Several placebo-controlled studies have shown that the clinical symptoms of some, but not all patients, respond very significantly to treatment with TNFα blockers such as infliximab [2]. However, these TNFα blockers are very costly. In most countries, their uses are either not supported by health providers or only under strict administrative control. It will be very useful if biomarkers are available so that practicing physicians can rapidly and reliably distinguish good from poor responders. Current gold standards to measure therapeutic response, such as the Assessment in Ankylosing Spondylitis (ASAS) Internation- al Working Group Criteria, are reserved only for inves- tigators and not used by practicing physicians [3]. In addition, these response criteria rely heavily on subjective self-evaluation by the patients. The only blood tests currently used in clinical practice are the two acute phase reactants erythrocyte sedimentation rate (ESR) and C- Clin Rheumatol (2008) 27:1429–1435 DOI 10.1007/s10067-008-0941-x C. Romero-Sánchez : J. Londoño : R. Valle-Oñate Spondyloarthropathy Group-Division of Rheumatology, Hospital Militar/Universidad de la Sabana, Bogotá, Colombia W. H. Robinson : B. H. Tomooka Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA F. Huang (*) : X. Deng : L. Zhang : C. Yang Department of Rheumatology, The Chinese PLA General Hospital, Beijing 100853, China e-mail: fhuang1964@yahoo.com D. T. Y. Yu Division of Rheumatology, Department of Medicine, University of California, Los Angeles, CA, USA