Clinical response to interferon-beta-1a may be linked to low baseline circulating BDCA1 myeloid dendritic cells Differential role of circulating dendritic cells and CD4+ regulatory T-cells in relapsing-remitting multiple sclerosis: a 1-year longitudinal study.
Many variables with association with better response to interferon-beta-1a (IFNbeta-1a) have been described, but none has yet been shown to be predictive of clinical response. In this real-life observational 1-year longitudinal study of 23 relapsing-remitting multiple sclerosis (RRMS) patients treated with subcutaneous IFNbeta-1a, we have shown a lower proportion of circulating myeloid dendritic cells (mDCs) than in healthy controls at baseline. Both univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were conducted to determine which variables (age, sex, baseline EDSS, MS relapse rates 1 year and 2 years before initiating IFNbeta-1a, mDCs and plasmacytoid (pDCs) subsets, activated and regulatory CD4(+) T-cells (T(Reg))) were associated with clinical response to IFNbeta-1a. During 1 year of treatment, we observed a shift towards lower proportions of CD123(+) pDCs expression and higher numbers and function of the T(Reg). Univariate analysis disclosed that MS activity was significantly associated with baseline BDCA1(+) mDCs below < or = 0.4% (p<0.0025). Cox model analysis revealed that baseline BDCA1(+) mDCs was the most closely associated factor with MS activity on IFN treatment during the 1-year follow-up (p<0.01). A better understanding of the rules that govern the T(Reg)-DC relationship will enable scientists to better manage the immune response in MS patients.
de Andrés
Clara
C
Department of Neurology, Gregorio Marañón University General Hospital, Madrid, Spain. claradeandres@hotmail.com
Aristimuño
Carol
C
Bartolomé
Manuel
M
de Las Heras
Virginia
V
Martínez-Ginés
Ma Luisa
ML
Arroyo
Rafael
R
Fernández-Cruz
Eduardo
E
Sánchez-Ramón
Silvia
S
D000328:Adult; D018949:Antigens, CD1; D000954:Antigens, Surface / Q000097:blood*; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D011446:Prospective Studies; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; D006023:Glycoproteins; D016899:Interferon-beta; D000068556:Interferon beta-1a