We report a case of an emmetropic woman with excessive daytime sleepiness in alternation with insomnia consistent with the diagnosis criteria of a non-24 h sleep-wake disorder. After being refractory to the usual non-pharmacologic and pharmacologic treatment, we detected a deficiency of vitamin B12, vitamin D3, and folic acid. Substitution of these treatments led to a return of a 24 h sleep-wake rhythm though this remained independent from the external light-dark cycle. The question arises whether the vitamin D deficiency could be regarded as an epiphenomenon or whether there is an up-to-date unknown connection to the inner zeitgeber.
The chemokine C-X-C- ligand 13 (CXCL13) is a major B cell chemoattractant to B cell follicles in secondary lymphoid organs (SLO) that proposedly recruits B cells to the cerebrospinal fluid (CSF) during neuroinflammation. CXCR5, the cognate receptor of CXCL13, is expressed on B cells and certain T cell subsets, in particular T follicular helper cells (Tfh cells), enabling them to follow CXCL13 gradients towards B cell follicles for spatial proximity, a prerequisite for productive T cell-B cell interaction. Tfh cells are essential contributors to B cell proliferation, differentiation, and high-affinity antibody synthesis and are required for germinal center formation and maintenance. Circulating Tfh cells (cTfh) have been observed in the peripheral blood and CSF. Furthermore, CXCL13/CXCR5-associated immune activities organize and shape adaptive B cell-related immune responses outside of SLO via the formation of ectopic lymphoid structures in inflamed tissues, including the central nervous system (CNS). This review summarizes the recent advances in our understanding of the CXCL13/CXCR5 immune axis and its role in vaccination, autoimmunity, and infection with a special focus on its relevance for intrathecal B cell activities in inflammatory CNS diseases.
B-Lymphocytes , Neuroinflammatory Diseases , Chemokine CXCL13 , Humans , Immunotherapy , Receptors, CXCR5 , T-Lymphocyte Subsets
