Fatemeh Kamankesh; Ali Ganji; Ali Ghazavi; Ghasem Mosayebi
Abstract
Background: Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes.Objective: To investigate ginger extract’s effect on reducing inflammation and improving the symptoms ...
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Background: Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes.Objective: To investigate ginger extract’s effect on reducing inflammation and improving the symptoms in the EAE model.Methods: The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-β), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation.Results: The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups.Conclusion: The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.
Maryam Jari; Javad Sadeghi allah abadi; Davood Fathi; Marzieh Attar; Zahra Maleki; Majid Shahbazi
Abstract
Background: Various factors contribute to the pathogenesis of Multiple Sclerosis (MS), one of which is Fibroblast Growth Factor 2 (FGF2). The function of FGF2 is pleiotropic. The investigation of the role of this factor in the myelination has produced conflicting results. Objective: To investigate the ...
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Background: Various factors contribute to the pathogenesis of Multiple Sclerosis (MS), one of which is Fibroblast Growth Factor 2 (FGF2). The function of FGF2 is pleiotropic. The investigation of the role of this factor in the myelination has produced conflicting results. Objective: To investigate the serum levels of FGF2 in patients with MS. Material and methods: Eighty patients with MS and eighty healthy volunteers with no history of inflammation or demyelinating disorders were included, and serum samples were collected to evaluate serum levels of FGF2 using the ELISA technique. Both groups had the same age and gender distribution. For analysis, the Mann-Whitney U test was used. Results: Patients with MS had considerably greater serum FGF2 levels than the control group (p = 0.005). There was no difference between the FGF2 level in men and women. Conclusion: Our data indicate that FGF2 levels may be related to the susceptibility of Iranian patients with MS. Further studies are required to analyze the involvement of FGF2 in enhancing the inflammatory process in MS.
Mohammad Asgharzadeh; Davoud Sanajou; Hossein Samadi Kafil; Mehdi Farhoudi; Daryoush Savadi Oskouei; Fatemeh Khaki-Khatibi; Fatemeh Ahmadi; Manouchehr Fadaee; Ali Vegari; Vahid Asgharzadeh; Jalil Rashedi; Behroz Mahdavi Poor; Pourya Gholizadeh
Abstract
Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes ...
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Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes and susceptibility to MS in the Iranian Azari population. Methods: IL-10-1082 A/G SNP and the CCR5-delta32 were genotyped in 152 patients suffering from MS and 242 healthy non-relatives by allele specific-PCR and simple PCR methods, respectively. Results: The frequencies of AA (37.6%) and AG (55.9%) genotypes of IL-10-1082 were significantly high in the control (p = 0.021) and MS patients (p = 0.015), respectively, with no statistical difference between these groups. There was no significant difference in the CCR5 gene based on the possession of wild/wild and wild/del32 genotypes between MS patients and the control group. The del32/del32 genotype was not seen in any of the investigated groups. Tobacco (cigarettes and hookahs) consumption was higher among the MS patients (p=0.004), and this has the potential to raise the risk of MS in both the individuals and their family. However, it had no significant relation with the frequency of different genotypes of the IL-10-1082 and the CCR5. Conclusion: Our finding conclude on possible role of AA genotype of IL-10 -1082 as a protective factor in MS.
Behrouz Gharesi-Fard; Maryam Zare; Eskandar Kamali-Sarvestani
Volume 14, Issue 4 , December 2017, , Pages 306-315
Abstract
Background: Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, ...
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Background: Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, such as antibody production against placental proteins, may lead to pregnancy-related disorders. The association between pregnancy complications and some autoantibodies including anti-phospholipid and anti-angiotensin II type-1 receptor antibodies are clear examples in this regard. Objective: To investigate the probable placental antigens that might be targeted by the antibodies in the sera of MS patients. Methods: Total placental proteins were extracted from normal fresh placentas and were separated using two-dimensional gel electrophoresis (2-DE) technique. The separated proteins were transferred onto a Polyvinylidene Fluoride (PVDF) membrane and blotted with the pooled sera of MS women or healthy controls (20 individuals in each group). The differentially blotted spot was identified by mass spectrometry and confirmed by western blot technique. Results: The results indicated that the women afflicted with MS had an antibody against placental HSP70kDa protein 5 (GRP78). Conclusion: In the present study, a new placental autoantigen candidate, which was targeted by antibody present in MS women sera, was found. The clinical importance of this finding regarding pregnancy complications in MS patients should be investigated by further experiments.
Forooz Peiravian; Hamid Rajaian; Afshin Samiei; Nasser Gholijani; Behrouz Gharesi-Fard; Pooneh Mokaram; Abbas Rahimi-Jaberi; Eskandar Kamali Sarvestani
Volume 13, Issue 3 , September 2016, , Pages 186-196
Abstract
Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles ...
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Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles of pro-inflammatory, Th1-, Th2-, and Th17-related cytokines were compared by quantitative multiplexed ELISA-based chemiluminescent assay in 44 RR-MS and 44 healthy age- and sex-matched individuals from the same ethnicity. Results: Among pro-inflammatory cytokines, the levels of IL-6 (p=0.003), IL-8 (p=0.05) and TNF-α (p=0.002) were higher in patients than controls, though IL-4 and IL-10 as well as ΣTh2 cytokines were lower in patients (p=0.05, p=0.02 and p=0.05, respectively). After gender classification, the higher levels of IL-4 in male patients remained significant and IL-13 also showed significantly higher levels in male patients compared to male controls (p=0.003 and p=0.05, respectively). A significant negative correlation was detected between EDSS and IL-10 or ΣTh2 levels (p=0.005). In addition, IL-1α (r=0.4, p=0.05) and IFN-γ (r=0.35, p=0.05) were also directly correlated with EDSS in female patients. Conclusions: Patients with RR‑MS who are in the relapse clinical phase exhibit higher levels of pro-inflammatory cytokines and reduction in protective Th2-related cytokines.
Mansour Salehi; Bahram Bagherpour; Vahid Shayghannejad; Farzaneh Mohebi; Rasool Jafari
Volume 13, Issue 2 , June 2016, , Pages 141-147
Abstract
Background: Management of multiple sclerosis (MS) is based on the usage of immunosuppressive and immune-modulating medications. Cytokines play an important role in the pathogenesis of MS. Objective: To evaluate the effects of rapamycin on the concentrations of Th1/Th2/Th17 serum cytokines in patients ...
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Background: Management of multiple sclerosis (MS) is based on the usage of immunosuppressive and immune-modulating medications. Cytokines play an important role in the pathogenesis of MS. Objective: To evaluate the effects of rapamycin on the concentrations of Th1/Th2/Th17 serum cytokines in patients with MS. Methods: Six patients with relapsing remitting MS as a case group and 6 healthy individuals as a control group were enrolled. The patients have been receiving 2 mg rapamycin daily for 6 months. The individuals in control group received nothing during 6 months of the experiment. Enzyme linked immunosorbent assay (Simultaneous Multi-Analyte ELISA) technique was used for determination of serum concentrations of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IFN-γ, TNF-α, G-CSF and TGF-β before and after therapy with rapamycin. Results: The mean absorbance of 10 out of the 12 studied cytokines showed reduction after the therapy with rapamycin including IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IFN-γ and TNF-α. The only statistically significant reduction was observed in the absorbance of IFN-γ (p=0.028). Two cytokines illustrated increase in the patients sera after the therapy, including G-CSF and TGF-β, but only increase in TGF-β was statistically significant (p=0.046). None of the studied cytokines in the control group varied significantly after 6 months. Conclusion: Based on the findings of this study, rapamycin has some immunosuppressive effects, such as decreasing IFN-γ, which can improve the quality of life of the patients with multiple sclerosis. Also the increased level of TGF-β may also have benefits on the disease, which needs further clinical studies.
Keyvan Ghasami; Fardin Faraji; Masoud Fazeli; Ali Ghazavi; Ghasem Mosayebi
Volume 13, Issue 1 , March 2016, , Pages 16-26
Abstract
Background: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. Objective: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled ...
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Background: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. Objective: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled clinical trial. Methods: Multiple sclerosis patients were randomized independently, in a double blind design, into one of two treatment groups. Control group (n=45) received 30 μg/week interferon β-1a via intra-muscular injection. Atorvastatin-treated group (n=50) received interferon β-1a similar to control group in addition to atorvastatin (40 mg/day) for 18-months. All clinical and immunological variables were measured at the baseline and at the end of the study. Results: There was no significant difference between the two groups in the expanded disability status scale scores and the number of gadolinium-enhancing lesions during the 18-month treatment period. After 18 months, the levels of interleukin (IL)-4, IL-10, transforming growth factor-β and serum ferric reducing antioxidant power in the atorvastatin treatment group were significantly higher than the control group. Levels of IL-17, TNF-α and lymphocyte proliferation in the atorvastatin treatment group were significantly lower than the control group. Conclusion: Although combined atorvastatin and interferon-β do not change the clinical course of MS, atorvastatin might have beneficial effects in MS treatment possibly through inducing anti-inflammatory responses.
Mahmood Soveid; Peyman Petramfar
Volume 13, Issue 1 , March 2016, , Pages 64-68
Abstract
High cortisol level in endogenous Cushing’s syndrome suppresses the immune system and after treatment there may be an over activity of immune reaction leading to autoimmune diseases mostly thyroid and rheumatologic disorders. This is the second reported case of multiple sclerosis developing after ...
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High cortisol level in endogenous Cushing’s syndrome suppresses the immune system and after treatment there may be an over activity of immune reaction leading to autoimmune diseases mostly thyroid and rheumatologic disorders. This is the second reported case of multiple sclerosis developing after treatment of Cushing’s syndrome. A 42-year old man is reported who presented with bone fracture and osteoporosis and diagnosed with Cushing’s disease. Six months after surgical treatment of his pituitary adenoma, he developed progressive multiple sclerosis. We conclude that after treatment of endogenous Cushing’s syndrome, the patients should be watched for development of autoimmune disorders including those affecting the central nervous system.
Azam Jamshidian; Mohammad Kazemi; Vahid Shaygannejad; Mansoor Salehi
Volume 12, Issue 4 , December 2015, , Pages 311-318
Abstract
Background: Lack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard ...
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Background: Lack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard treatment in many other neuro-immune disorders. Recent data suggest that Treg/Th17 counterbalance may indicate the boundaries between promotion and regulation of inflammatory responses in MS and Treg/Th17 ratio may be useful as a marker for monitoring the efficiency of MS therapies. Objective: To evaluate the effect of PE on the frequency and ratio of Treg/Th17 cells through concomitant measurement of the expression levels of Treg and Th17 lineage specific transcription factors, FOXP3 and RORC2, respectively. Methods: Peripheral blood mononuclear cells of 8 relapsed MS patients were obtained before and after a complete course of PE therapy and the FOXP3 and RORC2 mRNA levels were assayed using real-time PCR approach. Results: No significant change in the expression levels of individual transcription factors existed, but a significant increase in FOXP3/RORC2 ratio (p=0.036) was observed. Conclusions: Our results suggest that PE therapy influences Treg/Th17 ratio and this maybe a mechanism by which this procedure exerts its improving effects in MS disease.
Seyed Javad Hasheminia; Sayyed Hamid Zarkesh-Esfahani; Sepideh Tolouei; Vahid Shaygannejad; Hedaiatallah Shirzad; Morteza Hashemzadeh Chaleshtory
Volume 11, Issue 2 , June 2014, , Pages 74-83
Abstract
Background: Multiple sclerosis (MS) is a T cell mediated autoimmune disease with unknown etiology. Appropriate MS therapeutic strategies need thorough understanding of both disease etiology and pathogenesis mechanisms. Ligation of TLR-2 and TLR-4 stimulates the production of several cytokines leading ...
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Background: Multiple sclerosis (MS) is a T cell mediated autoimmune disease with unknown etiology. Appropriate MS therapeutic strategies need thorough understanding of both disease etiology and pathogenesis mechanisms. Ligation of TLR-2 and TLR-4 stimulates the production of several cytokines leading to CNS autoimmunity and neurodegenerative diseases. Objective: To find a relationship between MS disability and TLR-2 and TLR-4 expression on mononuclear cells in the blood of MS patients. Methods: Forty-five new case (NC) MS patients (33 females and 12 males) and 45 age and gender-matched healthy controls (HC) were recruited to the study. PBMCs were prepared and the expressions of TLR-2 and TLR-4 were assessed by flowcytometry technique using appropriate monoclonal antibodies. Results: Our results showed that the expression of TLR-2 and TLR-4 proteins in the patients group was significantly higher than that of healthy controls. TLR-2 but not TLR-4 was correlated with expanded disability status scale (EDSS) scores. Conclusion: High expressions of TLR-2 and TLR-4 may represent a state of innate immune activation in patients with MS.
Vahid Shaygannejad; Saeed Montazeri; Azam Jamshidian; Soheil Tahani; Marjan Gharagozloo; Fereshteh Ashtari; Sahar Vesal; Seyed Javad Hasheminia; Leila Dehghani
Volume 11, Issue 2 , June 2014, , Pages 134-138
Abstract
Background: Midkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration. Objective: To study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients. Methods: We ...
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Background: Midkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration. Objective: To study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients. Methods: We evaluated the MK level and its relationship with inflammatory cytokines (IL-17 and IL-23) and antiinflammatory ones (IL-10 and TGF-β) in multiple sclerosis (MS) patients. The serum concentrations of MK and cytokines were assessed by ELISA in 32 MS patients in comparison with 32 healthy subjects. Results: Our data showed that the MK concentration in MS patients is lower than healthy controls (341.15 ± 40.71 Pg/ml vs. 620.15 ± 98.61 Pg/ml, respectively, p=0.015). We also observed a significant decrease in IL-10, IL-23, and TGF-β cytokine levels in MS patients. There was a significant correlation between MK and IL-23 concentrations in our study (r = +0.829, p≤0.001). Conclusion: These results confirm a role for MK in inflammatory reactions in MS.
Zohreh Babaloo; Reza Khajir Yeganeh; Mehdi Farhoodi; Behzad Baradaran; Mohamadreza Bonyadi; Leila Aghebati
Volume 10, Issue 1 , March 2013, , Pages 47-54
Abstract
Background: Effector CD4+ T cell subsets play an important role in Multiple Sclerosis (MS). Interleukin-27 (IL-27) suppresses Th (Th1, Th2 and Th17) cells and dampens autoimmunity and tissue inflammation by promoting the generation of Type 1 regulatory T cells (Tr1). Objective: To identify the relative ...
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Background: Effector CD4+ T cell subsets play an important role in Multiple Sclerosis (MS). Interleukin-27 (IL-27) suppresses Th (Th1, Th2 and Th17) cells and dampens autoimmunity and tissue inflammation by promoting the generation of Type 1 regulatory T cells (Tr1). Objective: To identify the relative levels of IL-27 and IL-17A in MS disease. Method: In a case-control study, venous blood was collected from forty MS patients and forty-three healthy subjects as control group. Serum levels of IL-27 and IL-17A were measured by ELISA method. Results: A significant difference between serum IL-17A concentration in patients (120.68 ± 209.85 pg/ml) and control group (67.26 ± 117.76 pg/ml, p=0.016) was found. Serum IL-27 levels of the MS patients (159.7 ± 581.4 pg/ml) were significantly lower than control subjects (180.35 ± 507.84 pg/ml, p=0.001). Conclusion: Our findings show decreased levels of IL-27 against increasing IL-17A levels in patients group which may suggest the suppressive role of IL-27 on inflammatory process of MS.
Alireza Andalib; Hassan Doulabi; Mohammadreza Najafi; Mehdi Tazhibi
Volume 8, Issue 1 , March 2011, , Pages 1-10
Abstract
Background: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine ...
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Background: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine expression pattern of these lymphocyte subsets. Objective: This study was performed to measure chemokine receptor expression on CD4 T cells for evaluation of Th1/Th2 dominantly in IFN-β treated patients. Methods: flowcytometry was used to detect chemokine receptor expression on CD4 T cell population in PBMCs obtained from MS and healthy control groups. Twenty six MS patients participated in this study before and after IFN-β therapy and the same number of healthy individuals were included. Results: The percentage of lymphocytes was 41.28% ± 10.30 in the blood of MS group compared with 36.88% ± 5.51% in the control group (p=0.017). The CD4+CXCR3+ cells were 18.86% ± 8.46% in healthy group, 30.78% ± 9.8% in pre-treated MS patients and 21.06% ± 9.23% in posttreated group (p<0.001). The CD4+CCR4+ cell subsets were 27.35% ± 10.15% in healthy group; 28.17% ± 8.9% in pre-treated group and 34.20% ± 8.96% in the post- IFN-β treatment group. The subset of CD4+CCR4+ was found to be dominant after IFN- β therapy in comparison with the control group (p<0.001). CD4+CCR5+ percentage was 1.24% ± 0.92% in the healthy people, 1.23% ± 0.71% in the MS patients and 0.76% ± 0.49% in post-treatment status (p=0.003). CD4+CCR3+ cell subsets were 0.62% ± 0.67% in control group, 0.28% ± 0.26% in the MS patients (p=0.022) and 0.39% ± 0.54% in IFN-β treated patients (p=0.334). An association was found for CXCR3 expression in pre- and post- treatment status (r=0.840, p<0.001) as well as for CCR4+ expression (r=0.712, p<0.001) in the same groups. The Th1 response was dominant in pre-treatment states, and then it shifted to a Th2 dominant state after IFN-β treatment. Conclusion: We suggest that the chemokine receptor expression of Th1/Th2 cell subsets could be used for monitoring and the evaluation of the MS disease status.
Mandana Mohyeddin Bonab; Sepideh Yazdanbakhsh; Jamshid Lotfi; Kamran Alimoghaddom; Fatemeh Talebian; Farnaz Hooshmand; Ardeshir Ghavamzadeh; Behrouz Nikbin
Volume 4, Issue 1 , March 2007, , Pages 50-57
Abstract
Background: Mesenchymal stem cells (MSCs) with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteris-tics. These properties make them promising tools in cell and gene therapy. Objective: To evaluate the potential therapeutic applications ...
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Background: Mesenchymal stem cells (MSCs) with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteris-tics. These properties make them promising tools in cell and gene therapy. Objective: To evaluate the potential therapeutic applications of autologous MSC in improving clinical manifestations of MS patients. Methods: Ten patients were included in this pi-lot study. All had progressive disease that had not responded to disease modifying agents including Mitoxantrone. Their Expanded Disability Status Scale (EDSS) score ranged from 3.5 to 6. Patients were injected intrathecally with culture expanded MSCs. They were followed with monthly neurological assessment and a MRI scan at the end of the first year. Results: During 13 to 26 months of follow up (mean: 19 months), the EDSS of one patient improved from 5 to 2.5 score. Four patients showed no change in EDSS. Five patients’ EDSS increased from 0.5 to 2.5. In the functional system assess-ment, six patients showed some degree of improvement in their sensory, pyramidal, and cerebellar functions. One showed no difference in clinical assessment and three deterio-rated. The result of MRI assessment after 12 months was as following: seven patients with no difference, two showed an extra plaque, and one patient showed decrease in the number of plaques. Conclusion: This preliminary report emphasizes on the feasibility of autologous MSC for treatment of MS patients. However, in order to draw a definitive conclusion a larger sample size is required.
Alireza Nikseresht; Mohammad Ali Azizi; Behrouz Gharesi-Fard; Eskandar Kamali Sarvestani
Volume 3, Issue 3 , September 2006, , Pages 136-141
Abstract
Background: Multiple Sclerosis (MS), the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by ...
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Background: Multiple Sclerosis (MS), the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some FcγR genes are associated with various infectious and autoimmune diseases, probably due to their effects on different binding capacities of encoded receptors for IgG containing immune complexes. Objective: To investigate the importance of FcγR polymorphisms in susceptibility to MS. Method: One hundred and fifty MS patients and 136 age and sex matched controls were genotyped for FcγRIIA and FcγRIIIA gene polymorphisms using PCR-RFLP method. Result: The allelic and genotypic frequencies of the FcγRIIA and FcγRIIIA did not differ significantly between the MS patients and controls. There was no association between allelic polymorphism of FcγRIIIA and severity of disease based on Expanded Disability Status Scale (EDSS) score. However, significant association between inherited FcγRIIA genotype and disease activity (p=0.001) or progression index was revealed (p=0.014). EDSS values showed that FcγRIIA (H/H) and (H/R) genotypes were associated with a lower EDSS score in relapsing-remitting MS and in the total MS population (P=0.001) but not (R/R) genotype. Conclusion: Considering the detrimental role of autoantibodies in the pathogenesis of MS, our results suggest that the inherited FcγRIIA alleles could affect the severity of MS by influencing the clearance rate of immune complexes and autoantibodies. The results of the present study add the FcγRIIA gene to the gene networks which determine the severity of MS in southern Iran.
