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.
Similar content being viewed by others
References
Arababadi MK, Hassanshahi G, Azin H, Salehabad VA, Araste M, Pourali R et al (2010a) No association between CCR5 D 32 mutation and multiple sclerosis in patients of south-eastern of Iran. Lab Med 41:31–33
Arababadi MK, Mosavi R, Khorramdelazad H, Yaghini N, Zarandi ER, Araste M et al (2010b) Cytokine patterns after therapy with Avonex(R), Rebif(R), Betaferon(R) and CinnoVex in relapsing–remitting multiple sclerosis in Iranian patients. Biomark Med 4(5):755–759
Baker BJ, Akhtar LN, Benveniste EN (2009) SOCS1 and SOCS3 in the control of CNS immunity. Trends Immunol 30(8):392–400
Corcione A, Casazza S, Ferretti E, Giunti D, Zappia E, Pistorio A et al (2004) Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc Natl Acad Sci U S A 101(30):11064–11069
Derakhshan R, Arababadi MK, Ahmadi Z, Karimababadi MN, Salehabadi VA, Abedinzadeh M, et al (2011) Increased circulating levels of SDF-1 (CXCL12) in type 2 diabetic patients is correlated to disease state but is unrelated to polymorphism of the SDF-1β gene in the Iranian population. Inflammation [Epub ahead of print]
Giunti D, Borsellino G, Benelli R, Marchese M, Capello E, Valle MT et al (2003) Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS. J Leukoc Biol 73(5):584–590
Hassanshahi G, Patel SS, Jafarzadeh AA, Dickson AJ (2007) Expression of CXC chemokine IP-10/Mob-1 by primary hepatocytes following heat shock. Saudi Med J 28(4):514–518
Hassanshahi G, Rezvani ME, Arababadi MK, Shamsizadeh A, Mahmoodi M, Mousavi A et al (2009) Expression of regulated oncogen-alpha by primary hepatocytes following isolation and heat shock stimulation. Iran J Biotech 7(1):1–9
Hassanshahi G, Arababadi MK, Khoramdelazad H, Yaghini N, Zarandi ER (2010) Assessment of CXCL12 (SDF-1alpha) polymorphisms and its serum level in posttransfusion occult HBV-infected patients in southeastern Iran. Arch Med Res 41(5):338–342
Hess DC, Borlongan CV (2008) Stem cells and neurological diseases. Cell Prolif 41(Suppl 1):94–114
Kawasaki E, Ide A, Abiru N, Kobayashi M, Fukushima T, Kuwahara H et al (2004) Stromal cell-derived factor-1 chemokine gene variant in patients with type 1 diabetes and autoimmune thyroid disease. Ann N Y Acad Sci 1037:79–83
Klein RS, Rubin JB (2004) Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and plasticity. Trends Immunol 25(6):306–314
Kohler RE, Comerford I, Townley S, Haylock-Jacobs S, Clark-Lewis I, McColl SR (2008) Antagonism of the chemokine receptors CXCR3 and CXCR4 reduces the pathology of experimental autoimmune encephalomyelitis. Brain Pathol 18(4):504–516
Li M, Ransohoff RM (2008) Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol 84(2):116–131
Lindvall O, Kokaia Z (2006) Stem cells for the treatment of neurological disorders. Nature 441(7097):1094–1096
Malik M, Chen YY, Kienzle MF, Tomkowicz BE, Collman RG, Ptasznik A (2008) Monocyte migration and LFA-1-mediated attachment to brain microvascular endothelia is regulated by SDF-1 alpha through Lyn kinase. J Immunol 181(7):4632–4637
McCandless EE, Piccio L, Woerner BM, Schmidt RE, Rubin JB, Cross AH et al (2008) Pathological expression of CXCL12 at the blood–brain barrier correlates with severity of multiple sclerosis. Am J Pathol 172(3):799–808
McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121–127
O'Keeffe J, Gately CM, Counihan T, Hennessy M, Leahy T, Moran AP et al (2008) T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to alpha-galactosylceramide are impaired. J Neurol Sci 275(1–2):22–28
Pablos JL, Santiago B, Galindo M, Torres C, Brehmer MT, Blanco FJ et al (2003) Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol 170(4):2147–2152
Patrussi L, Baldari CT (2011) The CXCL12/CXCR4 axis as a therapeutic target in cancer and HIV-1 infection. Curr Med Chem 18(4):497–512
Poggi A, Catellani S, Fenoglio D, Borsellino G, Battistini L, Zocchi MR (2007) Adhesion molecules and kinases involved in gammadelta T cells migratory pathways: implications for viral and autoimmune diseases. Curr Med Chem 14(30):3166–3170
Pourazar A, Salehi M, Jafarzadeh A, Arababadi MK, Oreizi F, Shariatinezhad K (2005) Detection of HBV DNA in HBsAg negative normal blood donors. Iran J Immunol 2(3):172–176
Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska-Wieczorek A, Ratajczak J (2004) Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells 'hide out' in the bone marrow. Leukemia 18(1):29–40
Razmkhah M, Doroudchi M, Ghayumi SM, Erfani N, Ghaderi A (2005) Stromal cell-derived factor-1 (SDF-1) gene and susceptibility of Iranian patients with lung cancer. Lung Cancer 49(3):311–315
Sellebjerg F, Bornsen L, Khademi M, Krakauer M, Olsson T, Frederiksen JL et al (2009) Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology 73(23):2003–2010
Soriano A, Martinez C, Garcia F, Plana M, Palou E, Lejeune M et al (2002) Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A genotype, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. J Infect Dis 186(7):922–931
Terasaki M, Sugita Y, Arakawa F, Okada Y, Ohshima K, Shigemori M (2011) CXCL12/CXCR4 signaling in malignant brain tumors: a potential pharmacological therapeutic target. Brain Tumor Pathol 28(2):89–97
Watanabe MA, de Oliveira Cavassin GG, Orellana MD, Milanezi CM, Voltarelli JC, Kashima S et al (2003) SDF-1 gene polymorphisms and syncytia induction in Brazilian HIV-1 infected individuals. Microb Pathog 35(1):31–34
Weiner HL (2009) The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease? Ann Neurol 65(3):239–248
Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M et al (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279(5349):389–393
Acknowledgments
The authors of this article take this chance to thank all MS patients and healthy control individuals who voluntarily participated in this research project. This project was supported by a grant from Rafsanjan University of Medical Sciences.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Azin, H., Vazirinejad, R., Ahmadabadi, B.N. et al. 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. J Mol Neurosci 47, 431–436 (2012). https://doi.org/10.1007/s12031-011-9672-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-011-9672-6