Clinical response to interferon-β-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 (IFN beta-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 IFN beta-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 IFN beta-1a, mDCs and plasmacytoid (pDCs) subsets, activated and regulatory CD4(+) T-cells (T-Reg)) were associated with clinical response to IFN beta-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 <= 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. (C) 2009 Elsevier B.V. All rights reserved.