Multiple Sclerosis associated with low vitamin D – by B-cells which produce antibodies
Hypovitaminosis D upscales B-cell immunoreactivity in multiple sclerosis
Journal of Neuroimmunology May 15, 2016 Volume 294, Pages 18–26, DOI: http://dx.doi.org/10.1016/j.jneuroim.2016.03.011 |
Jürgen Haas, Alexander Schwarz, Mirjam Korporal-Kuhnke, Simon Faller, Sven Jarius, Brigitte Wildemann
Department of Neurology, University Hospital of Heidelberg, Germany
Highlights
B cells from MS patients with hypovitaminosis D exhibit enhanced immune responses ex vivo.
Hypovitaminosis D coincides with low vitamin D levels and increased frequencies of mature B-cell subtypes in the cerebrospinal fluid.
Vitamin D-supplementation attenuates B-cell immunoreactivities.
Background
While vitamin D is increasingly recognized as a potential immune regulator of MS disease activity, its impact on B lymphocytes, however, remains ill-defined.
Methods
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).
Results
B cells from MS patients with 25(OH)D serum levels <20 ng/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.
Conclusion
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.