COVID-19 pandemic and biological therapy in rheumatologic disorders: how to deal with?

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.

The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease caused by interaction of genetic, epigenetic, and environmental factors. One of the important epigenetic factors in SLE would be methylation of immune-related genes, such as FOXP3, which plays a role in activating the regulation and also the function of T cells. To date, the relationship between levels of serum bio-markers and the susceptibility to lupus in children has not been well-understood. In this study, the involvement of etiologic factors, such as methylation of FOXP3 gene, was investigated in children with SLE. METHOD: Twenty-four female children with SLE and 25 female healthy subjects without any history of autoimmune and inflammatory diseases were included in this study. Blood samples were obtained and DNA was extracted from the blood cells. The bisulphite method was used to convert the DNA using the MethylEdge™ Bisulfite Conversion System Kit. Then, methylation of the gene was investigated using Real Time methylation specific PCR. RESULTS: The FOXP3 DNA methylation in patients and healthy subjects was significantly different. While the median unmethylated DNA in patients was 0.57 ± 0.43, it was 0.97 ± 0.83 in healthy subjects (P = 0.012). The Demethylation Index in patients was 0.007 ± 0.003, significantly lower than in controls (0.014 ± 0.013; P = 0.012). CONCLUSIONS: The FOXP3 gene methylation in children with SLE was significantly higher than healthy subjects, which could possibly affect the level of gene expression. Therefore, one of the causes of increased immune response in SLE can be the lower expression of FOXP3 by hypermethylation of this gene

No disponible

The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease caused by interaction of genetic, epigenetic, and environmental factors. One of the important epigenetic factors in SLE would be methylation of immune-related genes, such as FOXP3, which plays a role in activating the regulation and also the function of T cells. To date, the relationship between levels of serum bio-markers and the susceptibility to lupus in children has not been well-understood. In this study, the involvement of etiologic factors, such as methylation of FOXP3 gene, was investigated in children with SLE. METHOD: Twenty-four female children with SLE and 25 female healthy subjects without any history of autoimmune and inflammatory diseases were included in this study. Blood samples were obtained and DNA was extracted from the blood cells. The bisulphite method was used to convert the DNA using the MethylEdge™ Bisulfite Conversion System Kit. Then, methylation of the gene was investigated using Real Time methylation specific PCR. RESULTS: The FOXP3 DNA methylation in patients and healthy subjects was significantly different. While the median unmethylated DNA in patients was 0.57±0.43, it was 0.97±0.83 in healthy subjects (P=0.012). The Demethylation Index in patients was 0.007±0.003, significantly lower than in controls (0.014±0.013; P=0.012). CONCLUSIONS: The FOXP3 gene methylation in children with SLE was significantly higher than healthy subjects, which could possibly affect the level of gene expression. Therefore, one of the causes of increased immune response in SLE can be the lower expression of FOXP3 by hypermethylation of this gene.

Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus

Introduction and objectives: Considering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. Materials and methods: A case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. Results: Analysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. Conclusion: These findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE

No disponible

Macrophage activation syndrome as a complication of rheumatologic disorders, a report from Iran.

The objective was to evaluate the clinical and laboratory manifestations and outcomes of the MAS cases in the context of systemic juvenile idiopathic arthritis (SJIA), systemic lupus erythematosus (SLE), Kawasaki disease, poly-articular juvenile idiopathic arthritis (PJIA). Twenty consecutive patients diagnosed with MAS between 2005 and 2016 entered the study. The cases were divided into two groups: in the first, MAS emerged in the context of a previously diagnosed rheumatologic disease, while in the second, MAS was the first presentation of a rheumatologic disease. In the other classification, the cases were divided into recurrent and non-recurrent cases. Laboratory data were recorded at three times: before MAS attack, during MAS attack, and 1 month after discharge from hospital. Nineteen cases with the median age of 5.9 (3.6-10) years entered the study. Four cases (21.1%) showed recurrent attacks of MAS. MAS was the first presentation of disease in 10 cases. The median age of the patients in the underlying disease group (10 years) was significantly higher than in the first presentation group [4.5(1.7-6.1) years, p=0.003]. The median fibrinogen value during MAS attack in the underlying disease group (601 mg/ dL) was also significantly higher than in the first presentation group (174 mg/dL, p=0.038). The platelet count during MAS attack in the recurrent group (30,500/microliter) was significantly lower than in the non-recurrent group (135,000/microliter, p=0.042). Our series of MAS cases demonstrated an overview of the symptoms, signs, laboratory manifestations, treatment, and prognosis of these cases. The higher median fibrinogen in MAS in the underlying disease group revealed that a decreasing level of fibrinogen in chronic disease is more significant than a single cut off value. Indeed, the lower platelet count in the recurrent MAS group may indicate greater platelet consumption due to organomegaly. Early diagnosis and treatment may save the patients' lives.

Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus.

INTRODUCTION AND OBJECTIVES: Considering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. MATERIALS AND METHODS: A case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. RESULTS: Analysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. CONCLUSION: These findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE.

A rare disease with a rare presentation: hemi-atrophy caused by fibromuscular dysplasia in a 27 month old girl.

We discuss the case of a 27-month-old girl afflicted with fibromuscular dysplasia. She presented with hemiatrophy of left upper and lower limbs, nail dystrophy, ulcers on the tips of her toes, cold and painful limbs, foot drop, and hypertension. The initial appearance started at 2 months of age and other diagnoses such as complex regional pain syndrome, reflex sympathetic syndrome, vasculitis and coagulation disorders had been considered. Angiography revealed that all the arterial branches of the left lower and upper limbs, from brachial to ulnar and radial, and from iliac and femoral to tibialis arteries were affected. Sural nerve biopsy confirmed the diagnosis. In the follow-up visits until 2 years after the patient's discharge she did not develop any new problem and her blood pressure was controlled by enalapril and amlodipine.

Exome sequencing revealed C1Q homozygous mutation in Pediatric Systemic Lupus Erythematosus

INTRODUCTION AND OBJECTIVES: Pediatric Systemic Lupus Erythematosus (pSLE) is an autoimmune disorder of children. Early disease onset raises the probability of genetic etiology and it is more severe than adult SLE. PATIENTS AND METHODS: Herein an eight-year-old girl with pSLE from consanguineous parents is reported. RESULTS: Although she was diagnosed as pSLE since the age of two years, Whole Exome Sequencing (WES) revealed a rare stop-gained C>T mutation in C1QA gene. The variant was validated and segregated in patient and the family. Furthermore, serum levels of the C1q protein were measured and found to be much lower than normal ranges. CONCLUSIONS: This study indicated that C1Q deficiency should be considered as a differential diagnosis of pSLE. Therefore, measurement of C1q should be recommended in all cases with pSLE

No disponible

Exome sequencing revealed C1Q homozygous mutation in Pediatric Systemic Lupus Erythematosus.

INTRODUCTION AND OBJECTIVES: Pediatric Systemic Lupus Erythematosus (pSLE) is an autoimmune disorder of children. Early disease onset raises the probability of genetic etiology and it is more severe than adult SLE. PATIENTS AND METHODS: Herein an eight-year-old girl with pSLE from consanguineous parents is reported. RESULTS: Although she was diagnosed as pSLE since the age of two years, Whole Exome Sequencing (WES) revealed a rare stop-gained C>T mutation in C1QA gene. The variant was validated and segregated in patient and the family. Furthermore, serum levels of the C1q protein were measured and found to be much lower than normal ranges. CONCLUSIONS: This study indicated that C1Q deficiency should be considered as a differential diagnosis of pSLE. Therefore, measurement of C1q should be recommended in all cases with pSLE.

Autoimmunity and its association with regulatory T cells and B cell subsets in patients with common variable immunodeficiency

Background: Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifests a wide clinical variability such as autoimmunity, as well as T cell and B cell abnormalities. Methods: A total of 72 patients with CVID were enrolled in this study. Patients were evaluated for clinical manifestations and classified according to the presence or absence of autoimmune disease. We measured regulatory T cells (Tregs) and B-cell subsets using flow cytometry, as well as specific antibody response (SAR) to pneumococcal vaccine, autoantibodies and anti-IgA in patients. Results: Twenty-nine patients (40.3%) have shown at least one autoimmune manifestation. Autoimmune cytopenias and autoimmune gastrointestinal diseases were the most common. A significant association was detected between autoimmunity and presence of hepatomegaly and splenomegaly. Among CVID patients, 38.5% and 79.3% presented a defect in Tregs and switched memory B-cells, respectively, whereas 69.0% presented CD21low B cell expansion. Among patients with a defect in Treg, switched memory and CD21low B cell, the frequency of autoimmunity was 80.0%, 52.2% and 55.0%, respectively. A negative correlation was observed between the frequency of Tregs and CD21low B cell population. 82.2% of patients had a defective SAR which was associated with the lack of autoantibodies. Conclusions: Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures (AU)

No disponible

Rheumatologic complications in a cohort of 227 patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most prevalent symptomatic type of human primary immunodeficiency diseases (PID). Clinically, CVID is characterized by increased susceptibility to infections and a wide variety of autoimmune and rheumatologic disorders. All patients with CVID registered in Iranian PID Registry (IPIDR) were enrolled in this retrospective cohort study. We investigated the frequency of rheumatologic diseases and its association with immunological and clinical phenotypes in patients with CVID. A total of 227 patients with CVID were enrolled in this study. The prevalence of rheumatologic disorders was 10.1% with a higher frequency in women than men. Most common rheumatologic manifestations were juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) followed by juvenile spondyloarthritis (JSpA) and undifferentiated inflammatory arthritis (UIA). Septic arthritis in patients with CVID with a history of RA and JIA was higher than patients without rheumatologic complication. Patients with CVID with a history of autoimmunity (both rheumatologic and non-rheumatologic autoimmunity) had lower regulatory T cells counts in comparison with patients without autoimmune disorders. There was an association between defect in specific antibody responses and negative serologic test results in patients with rheumatologic manifestations. JIA, RA, JSpA and UIA are the most frequent rheumatologic disorders in patients with CVID. Due to antibody deficiency, serologic tests may be negative in these patients. Therefore, these conditions pose significant diagnostic and therapeutic challenges for immunologists and rheumatologists in charge of the care for these patients.

Autoimmunity and its association with regulatory T cells and B cell subsets in patients with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifests a wide clinical variability such as autoimmunity, as well as T cell and B cell abnormalities. METHODS: A total of 72 patients with CVID were enrolled in this study. Patients were evaluated for clinical manifestations and classified according to the presence or absence of autoimmune disease. We measured regulatory T cells (Tregs) and B-cell subsets using flow cytometry, as well as specific antibody response (SAR) to pneumococcal vaccine, autoantibodies and anti-IgA in patients. RESULTS: Twenty-nine patients (40.3%) have shown at least one autoimmune manifestation. Autoimmune cytopenias and autoimmune gastrointestinal diseases were the most common. A significant association was detected between autoimmunity and presence of hepatomegaly and splenomegaly. Among CVID patients, 38.5% and 79.3% presented a defect in Tregs and switched memory B-cells, respectively, whereas 69.0% presented CD21low B cell expansion. Among patients with a defect in Treg, switched memory and CD21low B cell, the frequency of autoimmunity was 80.0%, 52.2% and 55.0%, respectively. A negative correlation was observed between the frequency of Tregs and CD21low B cell population. 82.2% of patients had a defective SAR which was associated with the lack of autoantibodies. CONCLUSIONS: Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures.

Approach to the Management of Autoimmunity in Primary Immunodeficiency.

Primary immunodeficiency diseases (PIDs) consist of a genetically heterogeneous group of immune disorders that affect distinct elements of the immune system. PID patients are more prone to infections and non-infectious complications, particularly autoimmunity. The concomitance of immunodeficiency and autoimmunity appears to be paradoxical and leads to difficulty in the management of autoimmune complications in PID patients. Therefore, management of autoimmunity in patients with PID requires special considerations because dysregulations and dysfunctions of the immune system along with persistent inflammation impair the process of diagnosis and treatment.

Association of interleukin-1 family gene polymorphisms with juvenile idiopathic arthritis in Iranian population

BACKGROUND: Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. MATERIALS AND METHODS: Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1alpha gene at position −889, IL-1beta gene at positions −511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. RESULTS: The CC genotype of IL-1Ra at Mspa-I 11100 position was found to be more frequent in patients with JIA compared to healthy individuals (P=0.03), although the CT genotype at the same position was significantly higher in the control group in comparison with patients with JIA (P=0.02). No significant differences were observed between the two groups of case and control for IL-1alpha (−889 C/T), IL-1beta (−511 C/T and +3962 C/T) and IL-1R (Pst-1 1970 C/T). CONCLUSION: The results of the present investigation suggest that certain IL-1Ra gene variants are associated with individuals' susceptibility to JIA. Nevertheless, further studies are required to establish the results of the current study

No disponible

Association of tumour necrosis factor-alpha G/A -238 and G/A -308 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disorder of unknown origin. As proinflammatory cytokines are known to contribute towards the pathogenesis of JIA, this case-control study was performed to examine the associations of certain single nucleotide polymorphisms (SNPs) of tumour necrosis factor-α (TNF-α) gene. Fifty-three patients with JIA participated in this study as patients group and compared with 137 healthy unrelated controls. Genotyping was performed for TNF-α gene at positions -308 and -238, using polymerase chain reaction with sequence-specific primers method. Results of the analysed data revealed a significant positive association for TNF-α gene at positions -308 and -238 for A allele in patients group compared with controls (P < 0.01). At the genotypic level, the frequency of TNF-α gene at positions -308 and -238 for GG genotype was discovered to be higher in the patients with JIA compared to the healthy controls (P < 0.01), while GA genotype at the same positions was observed to be less frequent in the case group than the controls (P < 0.01). At the haplotypic level, a significant positive association for TNF-α GG haplotype (positions -308, -238) together with a notable negative association for TNF-α AG and GA haplotypes at the same positions were detected in the patients group in comparison with the healthy individuals (P < 0.01). Cytokine gene polymorphisms might affect the development of JIA. Particular TNF-α gene variants could render individuals more susceptible to JIA..

Association of interleukin-1 family gene polymorphisms with juvenile idiopathic arthritis in Iranian population.

BACKGROUND: Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. MATERIALS AND METHODS: Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1α gene at position -889, IL-1ß gene at positions -511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. RESULTS: The CC genotype of IL-1Ra at Mspa-I 11100 position was found to be more frequent in patients with JIA compared to healthy individuals (P=0.03), although the CT genotype at the same position was significantly higher in the control group in comparison with patients with JIA (P=0.02). No significant differences were observed between the two groups of case and control for IL-1α (-889 C/T), IL-1ß (-511 C/T and +3962 C/T) and IL-1R (Pst-1 1970 C/T). CONCLUSION: The results of the present investigation suggest that certain IL-1Ra gene variants are associated with individuals' susceptibility to JIA. Nevertheless, further studies are required to establish the results of the current study.

Association of interleukin-2 and interferon-γ single nucleotide polymorphisms with Juvenile systemic lupus erythematosus

Purpose: Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. Materials and methods: The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at −330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. Results: Results of the analysed data revealed a negative allelic association for JSLE in IL-2 −330/T (P=0.02), as well as a positive allelic association for IL-2 −330/G (P=0.02). IL-2 GG genotype (−330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (−330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (−330, +166) GT haplotype was significantly higher in the patient group (P<0.001). Conclusion: IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE

No disponible

Association of Interleukin-2, but not Interferon-Gamma, single nucleotide polymorphisms with juvenile idiopathic arthritis

BACKGROUND: Cytokines, including interleukin-2 (IL-2) and interferon-gamma (IFN-γ), seem to play a role in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the associations of IL-2 and IFN-γ single nucleotide polymorphisms (SNPs) with susceptibility to JIA in an Iranian population. METHODS: enomic DNA of 54 Iranian patients with JIA and 139 healthy unrelated controls were typed for IL-2 (G/T at −330 and +166) as well as IFN-γ gene (A/T at +874), using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. RESULTS: A significantly higher frequency of the IL-2 −330 GG genotype (p < 0.01) was found in the JIA patients compared to the controls. However, the GT genotype at the same position was notably lower than in controls (p < 0.01). Moreover, IL-2 (−330, +166) GT haplotype was more frequent in patients with JIA in comparison with controls. No significant differences was observed between the two groups of case and control for IL-2 (G/T at +166) and IFN-γ (A/T at +874) SNPs. CONCLUSION: The results of the current study suggest that certain SNPs of IL-2 gene have association with individuals' susceptibility to JIA. However, further investigations are required to confirm the results of this study

No disponible

Association of interleukin-2 and interferon-γ single nucleotide polymorphisms with Juvenile systemic lupus erythematosus.

PURPOSE: Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. MATERIALS AND METHODS: The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at -330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. RESULTS: Results of the analysed data revealed a negative allelic association for JSLE in IL-2 -330/T (P=0.02), as well as a positive allelic association for IL-2 -330/G (P=0.02). IL-2 GG genotype (-330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (-330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (-330, +166) GT haplotype was significantly higher in the patient group (P<0.001). CONCLUSION: IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE.

Interleukin 10 and transforming growth factor beta 1 gene polymorphisms in juvenile idiopathic arthritis.

OBJECTIVES: The aim of this study is to identify the associations between interleukin 10 (IL-10) and transforming growth factor beta 1 (TGF-ß1) gene polymorphisms and individual susceptibility to juvenile idiopathic arthritis (JIA) in a group of Iranian patients. BACKGROUND: Cytokine genes, including IL-10 and TGF-ß1, are known to play important roles in the pathogenesis of JIA. METHODS: Using polymerase chain reaction with sequence-specific primers method, the frequency of alleles, genotypes and haplotypes of IL-10 (positions -1082, -819, -592) and TGF-ß1 (codon 10, codon 25) single-nucleotide polymorphisms (SNPs) were investigated in 55 patients with JIA as a case group and compared with 140 healthy unrelated controls. RESULTS: The G allele was significantly less frequent at TGF-ß1 codon 25 in patients with JIA than in the controls (p < 0.01). The frequency of CT genotype at TGF-ß1 codon 10 was found to be higher in healthy individuals in comparison with that in patients group (p = 0.04). We observed no differences in the frequency of alleles, genotypes and haplotypes of IL-10 gene between the groups of patients and controls. CONCLUSIONS: Considering the low frequency of existence of TGF-ß1 G allele at codon 25 as well as TGF-ß1 CT genotype at codon 10 in patients with JIA, it seems that these cytokine gene polymorphisms could play role as the protective factors against JIA.