Baseline T cell reactivity in multiple sclerosis is correlated to efficacy of interferon-beta.
BACKGROUND
Measuring proliferative responses of T lymphocytes is a simple, reproducible and widely used assay of immune competence. Evidence suggests a role of T cell reactivity in autoimmune diseases. Interferon (IFN)-beta blocks in vitro proliferation of human T cells.


OBJECTIVE
To assess (i) the relation between T cell proliferation and disease characteristics of MS patients, (ii) differences in T cell proliferation between subgroups and HC, and (iii) the predictive value of T cell proliferation for efficacy of IFN-beta.


METHODS
Proliferative responses were measured in phytohaemagglutinin (PHA), anti-CD2/CD28 and anti-CD3 stimulated whole blood of 189 MS patients and 249 healthy controls (HC). Forty-eight patients started treatment with IFN-beta. Based on EDSS progression, number of relapses and steroid interventions, patients were classified as either clinical responder or nonresponder to IFN-beta.


RESULTS
Significant differences between MS subgroups and HC were found in T cell responses upon both PHA stimulation (RR>HC: p=0.001 and SP>HC: p=0.001) and CD2/CD28 stimulation (RR>HC, SP>HC and PP>HC: all p values <0.001). No significant differences were found between the MS subgroups. A probability of 88% (95% CI, 71-95%) for a favorable response to IFN-beta was found with increased baseline proliferative T cell responses to PHA; a probability of only 16% (95% CI, 7-33%) with decreased values.


CONCLUSIONS
Our results suggest that the level of T cell proliferation in whole blood predicts efficacy of IFN-beta in MS.
Killestein
J
J
Department of Neurology, VU Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. J.Killestein@vumc.nl
Hintzen
R Q
RQ
Uitdehaag
B M J
BM
Baars
P A
PA
Roos
M T
MT
van Lier
R A W
RA
Polman
C H
CH
D000328:Adult; D000367:Age Factors; D002455:Cell Division / Q000187:drug effects* / Q000276:immunology; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D011237:Predictive Value of Tests; D012737:Sex Factors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D016896:Treatment Outcome
D016899:Interferon-beta