{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:55:37Z","timestamp":1790744137707,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During antimicrobial treatment of classic Whipple\u2019s disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4+ T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3+, predominantly CD45RO+CD4+ T cells. In the periphery, initial reduction of CD4+ cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4+ T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4+ T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei\u2013specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4+ T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.<\/jats:p>","DOI":"10.4049\/jimmunol.1202171","type":"journal-article","created":{"date-parts":[[2013,1,31]],"date-time":"2013-01-31T03:55:32Z","timestamp":1359604532000},"page":"2354-2361","source":"Crossref","is-referenced-by-count":44,"title":["Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple\u2019s Disease"],"prefix":"10.1093","volume":"190","author":[{"given":"Verena","family":"Moos","sequence":"first","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard E","family":"Feurle","sequence":"additional","affiliation":[{"name":"Deutsches Rotes Kreuz\u2013Krankenhaus Neuwied, Rheinische Friedrich-Wilhelms-Universit\u00e4t Bonn , 56564 Neuwied,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katina","family":"Schinnerling","sequence":"additional","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]},{"name":"Fachbereich Biologie, Chemie, Pharmazie, Freie Universit\u00e4t Berlin , 14195 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Geelhaar","sequence":"additional","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]},{"name":"Fachbereich Biologie, Chemie, Pharmazie, Freie Universit\u00e4t Berlin , 14195 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Friebel","sequence":"additional","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Allers","sequence":"additional","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Moter","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie und Hygiene, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Charit\u00e9 Campus Mitte , 10117 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Kikhney","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie und Hygiene, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Charit\u00e9 Campus Mitte , 10117 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Loddenkemper","sequence":"additional","affiliation":[{"name":"Gemeinschaftsspraxis f\u00fcr Pathologie , 12247 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Research Center ImmunoSciences, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]},{"name":"Medizinische Klinik m.S. Rheumatologie und Klinische Immunologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Erben","sequence":"additional","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]},{"name":"Research Center ImmunoSciences, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Fenollar","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Rickettsies Unit\u00e9 de Recherche sur les Maladies Infectieuses et Tropicales \u00c9mergentes, Centre National de la Recherche Scientifique\u2013Institut de Recherche pour le D\u00e9veloppment, Unit\u00e9 Mixte de Recherche 6236, Facult\u00e9 de M\u00e9decine , 13385 Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Raoult","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Rickettsies Unit\u00e9 de Recherche sur les Maladies Infectieuses et Tropicales \u00c9mergentes, Centre National de la Recherche Scientifique\u2013Institut de Recherche pour le D\u00e9veloppment, Unit\u00e9 Mixte de Recherche 6236, Facult\u00e9 de M\u00e9decine , 13385 Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schneider","sequence":"additional","affiliation":[{"name":"Medizinische Klinik I, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]},{"name":"Research Center ImmunoSciences, Campus Benjamin Franklin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 12203 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,3,1]]},"reference":[{"key":"2025032406385640200_r1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1473-3099(08)70042-2","article-title":"Whipple\u2019s disease: new aspects of pathogenesis and treatment","volume":"8","author":"Schneider","year":"2008","journal-title":"Lancet Infect. 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