The possible underlying pathophysiological mechanisms for development of multiple sclerosis in familial Mediterranean fever


Alpayci M. , Bozan N. , ERDEM S., GUNES M., ERDEN M.

MEDICAL HYPOTHESES, cilt.78, ss.717-720, 2012 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 78 Konu: 6
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1016/j.mehy.2012.02.017
  • Dergi Adı: MEDICAL HYPOTHESES
  • Sayfa Sayıları: ss.717-720

Özet

Patients with familial Mediterranean fever (FMF) have a susceptibility to the development of multiple sclerosis (MS). Here, we will propose the possible underlying pathophysiological mechanisms of this predisposition. Inflammation, disruption of blood-brain barrier (BBB), mitochondrial energy deficit, demyelination, and axonal damage, which play an important role in the pathogenesis of MS, may occur during the course of FMF. Most FMF patients have homozygous mutations in the MEFV gene that codes for the protein pyrin. Also, pyrin mutations were found about 3.5 times higher in the MS patients than the healthy control group. Pyrin is implicated in the maturation and secretion of the proinflammatory cytokine IL-1 beta. IL-1 beta is a major mediator of fever and systemic inflammation, and mononuclear cells from FMF patients release higher levels of IL-1 beta. Moreover, IL-1 plays a significant role in the regulation of the T-cells, and it is considered an essential cytokine for the Th cell differentiation that implicated in the MS pathogenesis. In addition, endothelial dysfunction and vasculitis in FMF may cause BBB breakdown that is the first step in the development of MS lesions. Apart from this, damage can occur in myelin and mitochondria proteins due to high body temperature that arises during the FMF attacks. Whereas the protein damage in myelin results in demyelination, and the protein damage in mitochondria causes lack of energy. Both situations play a part in the pathogenesis of MS. Due to mitochondrial energy deficit, remyelination may not be achieved, and therefore, axonal damage increases. Thus, at the end of these pathophysiological processes. MS findings may occur in the FMF patients especially with irregular use of colchicine. (C) 2012 Elsevier Ltd. All rights reserved.