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Reduced Peripheral and Mucosal Tropheryma whipplei-Specific Th1 Response in Patients with Whipple’s Disease¹

Verena Moos^2,*, Désirée Kunkel^*, Thomas Marth, Gerhard E. Feurle, Bernard LaScola, Ralf Ignatius^¶, Martin Zeitz^* and Thomas Schneider^*

^* Medizinische Klinik I, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; St. Josefs Krankenhaus, Zell/Mosel, Germany; Deutsches Rotes Kreuz Krankenhaus, Neuwied, Germany; Unité de Rickettsies, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6020, Faculté de Medicine, Marseille, France; and ^¶ Abteilung für Medizinische Mikrobiologie und Infektions-Immunologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

Whipple’s disease is a rare infectious disorder caused by Tropheryma whipplei. Major symptoms are arthropathy, weight loss, and diarrhea, but the CNS and other organs may be affected, too. The incidence of Whipple’s disease is very low despite the ubiquitous presence of T. whipplei in the environment. Therefore, it has been suggested that host factors indicated by immune deficiencies are responsible for the development of Whipple’s disease. However, T. whipplei-specific T cell responses could not be studied until now, because cultivation of the bacteria was established only recently. Thus, the availability of T. whipplei Twist-Marseille^T has enabled the first analysis of T. whipplei-specific reactivity of CD4⁺ T cells. A robust T. whipplei-specific CD4⁺ Th1 reactivity and activation (expression of CD154) was detected in peripheral and duodenal lymphocytes of all healthy (16 young, 27 age-matched, 11 triathletes) and disease controls (17 patients with tuberculosis) tested. However, 32 Whipple’s disease patients showed reduced or absent T. whipplei-specific Th1 responses, whereas their capacity to react to other common Ags like tetanus toxoid, tuberculin, actinomycetes, Giardia lamblia, or CMV was not reduced compared with controls. Hence, we conclude that an insufficient T. whipplei-specific Th1 response may be responsible for an impaired immunological clearance of T. whipplei in Whipple’s disease patients and may contribute to the fatal natural course of the disease.

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The JI 2006 177: 1373-1374. [Full Text]  

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