Immunopathology of immune reconstitution inflammatory syndrome in Whipple's disease.
During antimicrobial treatment of classic Whipple's 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-specific 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.
Medizinische Klinik I, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany. verena.moos@charite.de
Verena
V
Moos
Gerhard E
GE
Feurle
Katina
K
Schinnerling
Anika
A
Geelhaar
Julian
J
Friebel
Kristina
K
Allers
Annette
A
Moter
Judith
J
Kikhney
Christoph
C
Loddenkemper
Anja A
AA
Kühl
Ulrike
U
Erben
Florence
F
Fenollar
Didier
D
Raoult
Thomas
T
Schneider
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D054851:Tropheryma / Q000187:drug effects / Q000276:immunology*; D008061:Whipple Disease / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*
D000900:Anti-Bacterial Agents; D016753:Interleukin-10