Lymphocytic Infiltration and Expression of Inducible Nitric Oxide Synthase in Human Duodenal and Colonic Mucosa Is a Characteristic Feature of Ankylosing Spondylitis

DOMINIQUE LAMARQUE, JEANNE TRAN VAN NHIEU, MAXIME BREBAN, CHRISTOPHE BERNARDEAU, NADINE MARTIN-GARCIA, ZOLTAN SZEPES, JEAN-CHARLES DELCHIER, BRENDAN WHITTLE, and PASCAL CLAUDEPIERRE

ABSTRACT.

Objective. In patients with ankylosing spondylitis (AS), inflammatory processes have been detected in the ileal and colonic mucosa. The inducible isoform of nitric oxide synthase (iNOS) may be expressed early in the inflammatory process. We investigated iNOS activity and lymphocytic infiltration in the duodenum and colon in patients with AS and ulcerative colitis compared with controls.

Methods. Gastroscopy with duodenal biopsies and/or colonoscopy with biopsies were conducted in 42 patients with AS treated or not treated with nonsteroidal antiinflammatory drugs (NSAID), in 15 with ulcerative colitis, and in 46 controls. Lymphocytic infiltration in the lamina propria and intraepithelial infiltration were quantified by histological score. iNOS expression was assessed by immunohistochemistry with monoclonal antibodies, and iNOS activity was determined by radiochemical assay.

Results. Endoscopic examination of the gastroduodenal or colonic mucosa did not reveal macroscopic lesions in the AS patients. In the duodenum, mucosal lymphocytic infiltration was found in 83.3% of the AS group compared to 48.6% of controls (p = 0.02), and was independent of the NSAID intake. Intraepithelial lymphocyte infiltration was increased in both duodenum and colon in AS patients compared to controls. iNOS activity in duodenum and colon and expression of iNOS protein in lamina propria inflammatory cells was increased in AS patients compared to controls.

Conclusion. Lymphocytic infiltration and iNOS expression and activity were detected in duodenal and colonic mucosa from patients with AS. Such findings may indicate an inflammatory process in the small intestine and colon of patients with AS. (J Rheumatol 2003;30:2428-36)

Key Indexing Terms:

ANKYLOSING SPONDYLITIS
NITRIC OXIDE
COLITIS
DUODENUM
INFLAMMATION

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From the Institut National de la Santé et de la Recherche Médicale (INSERM) U99, Department of Gastroenterology, Department of Pathology, Department of Rheumatology, AP-HP Hôpital Henri Mondor, Créteil, France; INSERM U477 and the Institute of Rheumatology, AP-HP Hôpital Cochin, Paris, France; and The William Harvey Research Institute, St. Bartholomew's and Royal London School of Medicine and Dentistry, London, United Kingdom.

D. Lamarque, MD, PhD, Praticien-Hospitalier, INSERM U99 and Department of Gastroenterology, AP-HP Hôpital Henri Mondor; J. Tran Van Nhieu, MD, PhD, Maître de Conférence des Universités, Department of Pathology, AP-HP Hôpital Henri Mondor; C. Bernardeau, MD, Chef de Clinique-Assistant, INSERM U477 and Institute of Rheumatology, AP-HP Hôpital Cochin; M. Breban, MD, PhD, Maître de Conférence des Universités, INSERM U477 and Institute of Rheumatology, AP-HP Hôpital Cochin; N. Martin-Garcia, MD, Assistant, Department of Pathology, AP-HP Hôpital Henri Mondor; Z. Szepes, MD, PhD, Assistant, INSERM U99, AP-HP Hôpital Henri Mondor; J.C. Delchier, MD, Professor of Gastroenterology, Department of Gastroenterology, AP-HP Hôpital Henri Mondor; B.J.R. Whittle, PhD, DSc, Professor of Applied Pharmacology, The William Harvey Research Institute; P. Claudepierre, MD, Department of Rheumatology, AP-HP Hôpital Henri Mondor.

Address reprint requests to Dr. D. Lamarque, Service d'Hépatologie et de Gastroentérologie, AP-HP Hôpital Henri Mondor, F-94010 Créteil, France. E-mail: dominique.lamarque@bch.ap-hop-paris.fr

Submitted August 12, 2002; revision accepted March 28, 2003.

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