From brain to brawn

Abstract

After a subspecialized work day, when I opened the list of articles for the December issue of N2 I was reminded of how fascinating neurology is. There is an interesting group of studies that range from the CNS to the muscle and from acquired to innate immunity. For this corner, I selected only a few that represent the wide spectrum of topics. Alemtuzumab is a humanized monoclonal antibody that targets the membrane glycoprotein CD52, providing long-lasting suppression of disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). The underlying mechanisms resulting in these effects include complement-dependent cell lysis, antibody-dependent cellular cytotoxicity, and apoptosis leading to elimination of T cells. However, the effect of alemtuzumab on innate cells has been less investigated in patients with RRMS, and this is the main goal of the study of Gross et al.1 Innate immune cells comprise myeloid cells such as dendritic cells (DCs) and macrophages and lymphoid cells (ILCs), which include cytotoxic natural killer (NK) cells and 3 noncytotoxic tissue-resident subsets: ILC1, ILC2, and group 3 ILC (ILC3 and tissue-induced cells). The authors studied 12 patients with RRMS before and during alemtuzumab treatment and examined the effects on several of the above innate cell populations. They found that in comparison with CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets expressed lower amounts of CD52 on their surface. Interestingly, conventional DCs and plasmacytoid DCs that usually reconstitute rapidly in other immunosuppressive settings (e.g., allogeneic stem cell transplantation and immune conditioning) were found to be reduced 6 months after alemtuzumab treatment, although the interleukin (IL)–23 production in DCs was unchanged. In addition, within the ILC compartment, the subset of CD56bright NK cells expanded under alemtuzumab treatment but their cytolytic activity did not change. Interestingly, beneficial effects of daclizumab (a human monoclonal antibody against IL-2 receptor chain) are also associated with increasing numbers and function of the CD56bright NK cells in patients with RRMS, but different from alemtuzumab, daclizumab has effects on the cytolytic activity of NK cells. The authors acknowledge the limited number of patients and lack of functional assays in their study, but the findings are in line with the long-term efficacy of alemtuzumab, suggesting a remodeling of the innate immune system with preservation of immune competence in patients with RRMS.