title: Hypovitaminosis D upscales B-cell immunoreactivity in multiple sclerosis.
abstract: While vitamin D is increasingly recognized as a potential immune regulator of MS disease activity, its impact on B lymphocytes, however, remains ill-defined.
  
  
  
  We assessed the impact of vitamin D on B-cell proliferation and cytokine secretion ex vivo and screened for effects of hypovitaminosis D and vitamin D supplementation on the compartmentalized distribution of B-cell subtypes in peripheral blood and cerebrospinal fluid (CSF) from patients with relapsing remitting MS (n=95) and various neurologic and healthy controls (n=57).
  
  
  
  B cells from MS patients with 25(OH)D serum levels <20ng/ml, displayed enhanced immunoreactivity ex vivo as a consequence of more vigorous responses of CD27(+) memory phenotypes. Immune responses decreased when B cells from either source were co-cultured in the presence of vitamin D or when retesting B cells from MS patients after prolonged supplementation with vitamin D. Hypovitaminosis D was detectable in the serum of 40/95 MS patients, correlated with decreased vitamin D concentrations in CSF and with higher disease activity, and was paralleled by intrathecal accumulation of CD27(+) B-cell subtypes and plasma cells.
  
  
  
  B-cell immunoreactivity is attenuated by vitamin D. Our finding that vitamin D deficiency affects the intrathecal compartment and coincides with increased frequencies of effector B-cell subtypes in the CSF suggests that hypovitaminosis D might contribute to augmenting disease activity in the target organ and supports a potential benefit of vitamin D supplementation in MS.
authors.affiliation: Department of Neurology, University Hospital of Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas
authors.affiliation: Department of Neurology, University Hospital of Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schwarz
authors.affiliation: Department of Neurology, University Hospital of Heidelberg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Korporal-Kuhnke
authors.affiliation: Department of Neurology, University Hospital of Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Faller
authors.affiliation: Department of Neurology, University Hospital of Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jarius
authors.affiliation: Department of Neurology, University Hospital of Heidelberg, Germany. Electronic address: brigitte.wildemann@med.uni-heidelberg.de.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000473:pathology; D014807:Vitamin D / Q000494:pharmacology*; D014808:Vitamin D Deficiency / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications* / Q000473:pathology; D014815:Vitamins / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D014815:Vitamins; D014807:Vitamin D
keywords: B lymphocytes; B-cell immunoreactivity; Cerebrospinal fluid; Hypovitaminosis D; Multiple sclerosis; Vitamin D