Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis.
OBJECTIVE
To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models.


METHODS
We report four cases of corticosteroid-dependent ulcerative colitis (UC) and two Crohn's disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25(high) (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing.


RESULTS
Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-beta (mRNA) did not parallel that of FoxP3 mRNA.


CONCLUSIONS
The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.
Cuadrado
Emilio
E
Immunology Unit, Hospital Donostia, P(o) doctor Begiristain s/n, Donostia 20014, San Sebastian, Spain. emilio.cuadradodelbarrio@osakidetza.net
Alonso
Marta
M
de Juan
Maria-Dolores
MD
Echaniz
Pilar
P
Arenas
Juan-Ignacio
JI
D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D003424:Crohn Disease / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D016238:Cytapheresis / Q000379:methods*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta