Pregnancy-induced fluctuations in functional T-cell subsets in multiple sclerosis patients.
BACKGROUND
During pregnancy, especially during the third trimester, multiple sclerosis (MS) disease activity is reduced. It is not known which factors mediate this disease amelioration.


OBJECTIVE
To study whether the frequency of two important T-cell subsets, T-helper 17 (Th17) and regulatory T-cells (Treg), is altered in relation to pregnancy-induced MS disease amelioration.


METHODS
Each individual was tested longitudinally, after sampling of blood at timepoints before pregnancy, during the first and third trimester, and in the early post-partum period. Frequencies of Th17 cells were assessed after short (4 hours) re-stimulation of peripheral blood lymphocytes with PMA and ionomycin, followed by flow cytometry using CD4, CD45RO and IL-17A antibodies. To assess peripheral blood Treg frequencies, we used six-colour flow cytometry with antibodies against CD3, CD4, CD25, CD127, FoxP3 and HLA-DR, to specifically identify Treg.


RESULTS
Both MS patients (n = 9) and controls (n = 8) displayed unaltered Th17 frequencies during pregnancy. In contrast, circulating Treg frequency significantly decreased in MS patients (n = 15) during the first and third (p < 0.001) trimesters compared with the period before pregnancy. In the post-partum period, the frequency of circulating Treg again resurged back to near pre-pregnancy levels. In controls (n = 15) comparable frequency kinetics were observed in that post-partum a significant increase in circulating Treg frequency was detected compared with the first (p < 0.001) and third (p = 0.012) trimester.


CONCLUSIONS
Third trimester amelioration is not related to the fluctuation of circulating Th17 cells. Furthermore, a paradoxical decrease of immunosuppressive circulating Tregs can be observed during this phase, both in MS patients and controls.
Neuteboom
Rinze F
RF
Department of Neurology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
Verbraak
Evert
E
Wierenga-Wolf
Annet F
AF
van Meurs
Marjan
M
Steegers
Eric A P
EA
de Groot
Christianne J M
CJ
Laman
Jon D
JD
Hintzen
Rogier Q
RQ
D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004185:Disability Evaluation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism*; D016014:Linear Models; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology*; D009426:Netherlands; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000276:immunology*; D011263:Pregnancy Trimester, Third / Q000276:immunology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D020381:Interleukin-17