Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximab.
BACKGROUND
Under experimental chronic inflammation, tumor necrosis factor (TNF)-alpha plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-alpha is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients.


METHODS
Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells.


RESULTS
A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients.


CONCLUSIONS
Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation.
Di Sabatino
Antonio
A
First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy. a.disabatino@smatteo.pv.it
Rosado
M Manuela
MM
Cazzola
Paolo
P
Biancheri
Paolo
P
Tinozzi
Francesco Paolo
FP
Laera
Maria Rita
MR
Cantoro
Laura
L
Vanoli
Alessandro
A
Carsetti
Rita
R
Corazza
Gino Roberto
GR
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000276:immunology*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D000069285:Infliximab; D008297:Male; D008857:Microscopy, Interference; D008875:Middle Aged; D013154:Spleen / Q000502:physiology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab