High-Throughput Multi-Analyte Luminex Profiling Implicates Eotaxin-1 in Ulcerative Colitis

• Published in: PloS one Vol. 8; no. 12; p. e82300
• Main Authors: Coburn, Lori A., Horst, Sara N., Chaturvedi, Rupesh, Brown, Caroline T., Allaman, Margaret M., Scull, Brooks P., Singh, Kshipra, Piazuelo, M. Blanca, Chitnavis, Maithili V., Hodges, Mallary E., Rosen, Michael J., Williams, Christopher S., Slaughter, James C., Beaulieu, Dawn B., Schwartz, David A., Wilson, Keith T.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.12.2013; Public Library of Science (PLoS)
• Subjects: Active control; Adult; Analysis; Analytical chemistry; Animals; Apoptosis; Arginine; Cancer; Chemokine CCL11 - metabolism; Chemokines; Citrobacter; Colitis, Ulcerative - blood; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - metabolism; Colon; Colonoscopy; Cytokines; Dextran; Dextran sulfate; Dextrans; Disease control; Eotaxin; Etiology; Family medical history; Female; Gastritis - blood; Gastritis - metabolism; Gastritis - microbiology; Gastroenterology; Granulocyte colony-stimulating factor; Health aspects; Helicobacter infections; Helicobacter pylori; Helicobacter pylori - pathogenicity; Hepatology; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Leukocytes (eosinophilic); Male; Medical research; Medical screening; Medicine; Mice; Mice, Inbred C57BL; Middle Aged; Multiplexing; Nutrition; Oxazolone; Oxazolone - toxicity; Pathogenesis; Patients; Prospective Studies; Rodents; Sodium; Sulfates; Target recognition; Therapy; Tissues; Ulcerative colitis; Veterans; United States > US; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082300

Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies.