The SDF-1 3′A Genetic Variation of the Chemokine SDF-1α (CXCL12) in Parallel with its Increased Circulating Levels is Associated with Susceptibility to MS: A Study on Iranian Multiple Sclerosis Patients

Abstract

Immune system-related factors are important in pathogenesis of multiple sclerosis. The CXC chemokine SDF-1α (CXCL12) is involved in the immune responses. Hence, the aim of this study was to investigate the association between serum levels of SDF-1α (CXCL12) and its gene polymorphisms at position +801 with multiple sclerosis. In this experimental study, blood samples were collected from 100 multiple sclerosis patients and 100 healthy controls on EDTA pre-coated tubes. DNA was extracted and DNA samples were analyzed for SDF-1α (CXCL12) polymorphisms using PCR-RLFP in patients and controls. The serum levels of SDF-1α (CXCL12) were measured by ELISA. Demographic data were also collected by a questionnaire which was designed specifically for this study. Our results showed a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of SDF-1α (CXCL12). Our results also showed that serum levels of SDF-1α (CXCL12) were markedly higher in patients than healthy controls, but no association was observed between SDF-1α (CXCL12) polymorphism and its serum levels. The results of this study might suggest the serum levels of SDF-1α (CXCL12) and its polymorphism play an important role in pathogenesis of multiple sclerosis. It is also worth noting that these factors could probably use as pivotal biological markers in the diagnosis of MS.

The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis

“…Astrocytes are also the source of CXCL10 in both human and mouse EAE models [29,59,78], and evidence from these models demonstrates that both TNF-α and IFN-γ (as members of the proinflammatory cytokines) regulate CXCL10 expression in cell lines [79] as well as a rat model [48]. …”

CXCL12 and CXCR4 in the Peripheral Blood of Patients with Parkinson’s Disease

“…To the best of our knowledge, this is the first report of CXCL12 level in serum of PD patients. Azin et al reported that CXCL12 serum level in Iranian MS patients was significantly higher than controls [21]. In contrast, a reduction in CXCL12 serum levels has also been shown in early Alzheimer’s disease (AD) [22].…”

Significant Role(s) of CXCL12 and the SDF-1 3′A Genetic Variant in the Pathogenesis of Multiple Sclerosis

“…Stromal cell-derived factor-1 (SDF-1; known as CXCL12 in the recent chemokine nomenclature) is described as a CXC chemokine [unpubl. data and [16][17][18]. This biological compound is involved in chemotaxis and it is active on T lymphocytes and monocytes but does not affect neutrophils.…”

“…More recent reports indicate that the serum and/or tissue expression of CXCL12 is increased in various autoimmune diseases, including MS [unpubl. data and 2, 18,19 ]. Therefore, it appears that the genetics of CXCL12 may be altered in MS and other autoimmune inflammation-related disorders.…”

“…Two specific transmembrane protein receptors, i.e., CXCR4 and CXCR7, serve as receptors for CXCL12 and induce a rapid and transient rise in intracellular levels of calcium ions and result in development of the biological phenomenon of chemotaxis. However, CXCR7 is a scavenger receptor and does not signal with a downstream path similar to that with which CXCR4 is activated [17][18][19]. It has been verified that CXCL12 actively induces monocyte migration while inhibiting monocyte adhesion via the LYN kinase (Lyn is a member of the Src family of protein tyrosine kinases).…”