Journal of Pathology J Pathol 2002; 198: 517–522. Published online 4 October 2002 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/path.1235 Original Paper Increase in lymphoid follicles and leukocyte adhesion molecules emphasizes a role for the gut in spondyloarthropathy pathogenesis P Demetter, 1 * JA Van Huysse, 1 F De Keyser, 2 N Van Damme, 2 G Verbruggen, 2 H Mielants, 2 M De Vos, 3 EM Veys 2 and CA Cuvelier 1 1 Department of Pathology, Ghent University Hospital, Ghent University, Belgium 2 Department of Rheumatology, Ghent University Hospital, Ghent University, Belgium 3 Department of Gastroenterology, Ghent University Hospital, Ghent University, Belgium *Correspondence to: P Demetter, Department of Pathology, Ghent University Hospital, 5 Blok A, De Pintelaan 185, 9000 Gent, Belgium. E-mail: pieter.demetter@rug.ac.be Received: 19 April 2002 Accepted: 20 May 2002 Abstract The aim of this study was to investigate the expression of leukocyte adhesion molecules and the number of lymphoid follicles in gut mucosa of patients with spondyloarthropathy (SpA) in comparison with controls, in search for early immune alterations in the development of SpA-related gut inflammation. Histological evaluation and immunohistochemistry were per- formed on the ileum and colon of 14 SpA patients without macroscopic or microscopic gut inflammation and those of 21 controls. Lymphoid follicles were counted and immunohisto- chemical staining for leukocyte adhesion molecules, lymphocyte subtypes, macrophages, and plasma cells was scored semi-quantitatively. The number of lymphoid follicles was increased in both the ileum (p < 0.01) and the colon (p < 0.01) of SpA patients. SpA ileum showed an increase in leukocytes expressing CD11c (p < 0.01), whereas CD11a + (p < 0.02) and VCAM-1 + cells (p < 0.05) were increased in SpA colon. Macrophages, characterized by the expression of CD68, were more numerous in colonic mucosa from SpA patients (p < 0.05). The amount of lymphoid follicles and lamina propria mononuclear cells expressing CD11a, CD11c, and VCAM-1 was increased in non-inflamed gut mucosa from SpA patients. These findings might point to increased antigen handling and presentation and augmented matu- ration of na¨ ıve T cells towards memory T cells in the SpA gut, which supports the concept that the gut is involved in the pathogenesis of SpA. Copyright  2002 John Wiley & Sons, Ltd. Keywords: spondyloarthropathy; gut; adhesion molecules; follicles; pathogenesis Introduction The spondyloarthropathies are a group of related inflammatory disorders which share some clinical, biological, therapeutic, and genetic characteristics [1]. The concept identifies a distinct entity, different from other rheumatic diseases. The target organs are not only the joints, but also the axial skeleton, the enthesis, the eye, the urogenital tract, the skin, and the gut. Sub- clinical inflammatory gut lesions are found in 25 – 75% of patients with spondyloarthropathy (SpA) and 6% of these patients evolve over time to clinically overt Crohn’s disease [2–4]. The mechanisms that link the joint and the gut in SpA are still unclear. An interesting hypothesis on the relationship between the gut and the joint includes a re-circulation of memory T cells from the gut to the synovium. Previously, such a migratory pathway has been termed ‘gut-iteropathy’ [5]. The re-circulation of lymphocytes throughout the body is an essential phenomenon in the whole cas- cade of immune surveillance [6]. Na¨ ıve lymphocytes matured in primary lymphoid organs (bone marrow and thymus) probably move continuously between the various lymphoid organs until they die or respond to their cognate antigen [7]. The maturation of na¨ ıve T cells towards antigen-specific memory cells occurs in specially organized microenvironments (secondary lymphoid organs), where na¨ ıve lymphocytes respond for the first time to specific antigens and undergo an antigen-initiated differentiative process; that is, the virgin to memory-effector transition. In the gut, this tissue compartment is represented by the lymphoid fol- licles. Tertiary lymphoid tissues include all other body tissues, including the gut lamina propria and the syn- ovium. Under normal conditions, these contain only a limited number of lymphoid cells. However, in the presence of inflammatory stimuli, they may become more populated with immune competent cells, includ- ing memory lymphocytes and effector cells, which can be re-stimulated by antigen. The process of lymphocyte trafficking is mainly reg- ulated by receptors belonging to a group of molecules referred to as adhesion molecules, which constitute Copyright  2002 John Wiley & Sons, Ltd.