TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-κB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients.

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-ß, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikßα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses. MATERIALS AND METHODS: Ten OA patients' synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-ß, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikßα and pIkßα. RESULTS: The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-ß, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikßα which was increased by LPS treatment. CONCLUSION: According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.

Determination of IL-23 receptor expression and gene polymorphism (rs1884444) in Iranian patients with ankylosing spondylitis.

BACKGROUND: Through investigating genetic variations, it has been demonstrated that single nucleotide polymorphisms (SNPs) in the IL-23 receptor (IL23R) gene have a critical role in the pathophysiology of ankylosing spondylitis (AS). Here, we investigated whether the IL23R variant (rs1884444) is associated with AS in the Iranian population. METHODS AND MATERIAL: In this research, we analyzed rs1884444 in a group of 425 patients with AS and 400 matched controls. For DNA extraction, the phenol/chloroform technique was utilized. Peripheral blood mononuclear cells (PBMCs) were obtained from the whole blood of 39 patients and 43 healthy controls and total RNA was extracted. Genotyping was performed by amplification-refractory mutation system (ARMS)-PCR method. Afterward, the expression level of IL23R was analyzed by the real-time quantitative (Q)-PCR method. RESULTS: We observed no significant association between the distribution of alleles and genotypes of rs1884444 and susceptibility to AS. In addition, the expression level of IL23R did not differ between PBMCs from AS patients compared to the control group (P = 0.167). Furthermore, the relative expression level of IL23R was positively correlated with the BASDAI (P < 0.01) and BASFI (P < 0.05) scores of the patients. CONCLUSION: It appears that IL23R polymorphism (rs1884444) and the level of gene expression might not contribute to the susceptibility to AS in the Iranian population. The correlation of IL23R expression with the level of BASDAI and BASFI scores in patients may be due to the role of the IL-23/IL-23R signaling cascade in inflammation and exert a critical role in the development of AS.

Evaluation of apical transportation and centering ability of three single-file systems in severely curved canals using micro-computed tomography.

Background: This study aimed to compare the apical transportation and centering ability of One Curve, HyFlex EDM, and EdgeFile X1 in curved mesiobuccal and mesiolingual canals of mandibular first molars. Materials and Methods: In this in vitro experimental study, 60 mesiobuccal and mesiolingual canals of the mandibular first molars with a minimum length of 19 mm and 25°-40° curvature were randomly divided into three groups (n = 20) for root canal preparation with One Curve, HyFlex EDM, and EdgeFile X1. After access cavity preparation and confirming the glide path, the baseline micro-computed tomography (micro-CT) scans were obtained, and the root canals were instrumented with the respective systems according to the manufacturers' instructions. Apical transportation and centering ability were assessed at 1, 3, 5, and 7 mm from the apex by comparing pre- and postinstrumentation micro-CT scans. One-way ANOVA, independent t-test, and Duncan's post hoc test were used to statistically compare the groups, and data were analyzed by SPSS version 24 (alpha = 0.05). Results: The three groups were not significantly different regarding apical transportation at 5 and 7 mm from the apex (P > 0.05). At 1 mm level, One Curve caused significantly lower apical transportation; while, at 3 mm level, HyFlex EDM resulted in significantly higher apical transportation (P < 0.05). No significant difference was noted in the centering ability of the three groups at 1, 3, and 5 mm from the apex (P > 0.05). At 7 mm level, EdgeFile X1 showed significantly lower centering ability (P < 0.05). Conclusion: One Curve caused lower canal transportation in the apical third compared with EdgeFile and HyFlex EDM, but no significant difference was noted among the three in the coronal third of the roots.

The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients. METHOD: One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes. RESULTS: The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1Asn80 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls. CONCLUSION: Our results suggest that the presence HLA-C1Asn80 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.

Potential Roles for B cells and Autoantibodies in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that predominantly affects young males. AS is a condition in which the spine and sacroiliac joints become inflamed. More specifically, most AS patients experience spine malformations over time, resulting in functional incapability. The etiopathogenesis of AS is a complex combination of genetic predisposition and environmental factors. Extensive studies on AS have revealed the central role of genetics and immune reactions in its etiology. However, an utmost agreement has yet to be created. The available evidence suggests that both autoinflammation and T-cell-mediated autoimmune processes have significant roles in the disease process of AS. So far, B cells have obtained moderately little attention in AS pathogenesis, primarily because of the absence of disease-defining autoantibodies. However, against general dogma, evidence is mounting showing B cell involvement. Disruptions depict this in circulating B cell populations, the increased expression of immunoglobulin (Ig)G, IgA, and IgM, and B cell infiltration within the axial skeleton of AS patients. Meanwhile, compared to many other inflammatory autoimmune disorders, AS has no disease-specific autoantibodies that help disease diagnosis. This study has provided an overview of the B lymphocytes and antibodies' role in AS pathogenesis. It also introduces autoantibodies that can be the prognosis and diagnosis biomarkers of AS.

Comparison of the number of bacterial colonies among four types of suture threads using simple loop method following periodontal surgery in patients with periodontitis: A single-blind randomized clinical trial.

Background: This study investigated the number of bacterial colonies in four types of suture threads, including silk, nylon, monocryl, and monocryl plus after periodontal surgery in patients with moderate-to-severe periodontitis. Materials and Methods: In this single-blind randomized clinical trial, a total of 12 patients with periodontitis who required periodontal flap surgery in all quadrants were included. One type of suture, either silk, nylon, monocryl, or monocryl plus (coated with triclosan), was used following each surgery in each quadrant. Sutures (3 mm) were removed from the mid, posterior, and anterior regions of the flap 7 days postoperatively, and placed in a tube-containing buffer medium to transfer to the culture medium in a laboratory. Then, the bacterial colonies on each culture medium were counted manually. Finally, the mean number of grown colonies (anaerobic and aerobic) was computed and compared in each group of sutures. Data were analyzed by SPSS (Version 20) using the repeated measures ANOVA and least significant difference follow-up tests (α = 0.05). Results: The findings of this study indicated a significantly higher mean number of aerobic, anaerobic, and aerobic-anaerobic colonies in silk suture than in the other three types of sutures (P < 0.05). However, no significant difference was observed among other types of sutures (P > 0.05). Conclusion: The results of this study showed that silk suture had a higher bacterial adhesion (aerobic, anaerobic, and aerobic-anaerobic) than monofilament sutures, including nylon, monocryl, and monocryl plus. Moreover, no significant difference was found among the monofilament sutures in the number of colonies grown on them.

Translation and validation of the Persian version of the scleroderma health assessment questionnaire (SHAQ).

The present study aimed to translate and validate the Scleroderma Health Assessment Questionnaire (SHAQ) for Persian-speaking patients (SHAQ-P), using a cross-sectional study. This cross-sectional study included SSc patients with 2013 ACR/EULAR criteria. The SHAQ was translated using a "forward-backward" method. HAQ-DI and SSc-HAQ scores were calculated from the patient-answered questionnaires. Rheumatology experts assessed the face and content validities of the SHAQ-P. Psychometric properties of the SHAQ-P were then assessed: Structural validity was analyzed using principal component factor analysis. Discriminant and convergent validities were measured on subgroups of the initial patient population. Test-retest reliability was measured on patients who filled the SHAQ-P again after 1 month. The Scale-CVI-average (S-CVI/Ave) score for content validity was 88.7%. Face validity was measured to be 68.17% using the QQ10 questionnaire. Factor analysis revealed a two-factor structure with 20 out of 26 questions loading on the first factor (N = 285). One-way ANOVA showed that patients with a higher number of involved organs had higher average HAQ-DI and SSc-HAQ-scores (N = 60, P = 0.019 and 0.023, respectively). HAQ-DI and SSc-HAQ-scores were significantly correlated with the physical component score of SF36 (N = 31, correlation coefficient = - 0.65 and - 0.72, respectively). Reliability testing after one month demonstrated that HAQ-DI and SSc-HAQ-scores were significantly correlated with their initial (N = 40, correlation coefficient = 0.86 and 0.84, respectively), proving that the Persian SHAQ was a valid and reliable questionnaire to evaluate scleroderma patients' quality of life.

Upregulation of KAT2B and ESCO2 gene expression level in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune condition that causes progressive inflammation. It seems that alternations in epigenetic modifications contribute to RA development. The present study aimed to assess the expression pattern of K (lysine) acetyltransferase 1 (KAT1; HAT1) and lysine acetyltransferase 2B (KAT2B; PCAF), and the establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) in peripheral blood mononuclear cells (PBMCs) from RA patients. METHOD AND MATERIAL: In this case-control study, we studied 50 cases with RA in comparison to 50 age- and gender-matched healthy subjects. Separation of PBMCs samples from whole blood, extraction of RNA, and reverse transcription were performed. Gene transcript levels of KAT1, KAT2B, and ESCO2 were determined using SYBR green real-time quantitative PCR. RESULTS: Our results exhibited a significant upregulation in the expression levels of ESCO2 and KAT2B genes in patients with RA compared to normal individuals (P-value < 0.0001). Similarly, we observed higher expression of KAT1 in the patients' group when compared to the healthy controls, although the difference in expression level failed to show any significant changes (P-value = 0.485). Also, we found a positive correlation between ESCO2 and the level of erythrocyte sedimentation rate (ESR) in patients. CONCLUSION: Collectively, our results suggest that upregulated expression of KAT2B and ESCO2 genes may be correlated to RA development. Further studies with larger sample sizes are required for understanding the potential contribution of these enzymes in the pathology of RA. Key Points • Dysregulated expression level of epigenetics enzymes was observed in PBMCs from RA patients. • The expression of KAT2B was 2.44 times higher in the PBMCs of RA patients than in the healthy subjects. • The expression of ESCO2 was upregulated (2.75 times) in the PBMCs of RA patients compared to the control group. • There was a positive correlation between ESCO2 expression and the ESR level in patients.

Development of an Injectable Shear-Thinning Nanocomposite Hydrogel for Cardiac Tissue Engineering.

Bone marrow-derived mesenchymal stem cells (MSCs) offer a promising therapeutic method for cardiac tissue regeneration. However, to monitor the fate of MSCs for tissue repair, a better stem cell delivery carrier is needed. Developing a unique injectable and shear-thinning dual cross-linked hybrid hydrogel for MSC delivery for cardiac tissue engineering is highly desirable. This hydrogel was synthesised using guest: host reaction based on alginate-cyclodextrin (Alg-CD) and adamantane-graphene oxide (Ad-GO). Here, the role of macromere concentration (10 and 12%) on the MSC function is discussed. Our hybrid hydrogels reveal a suitable oxygen pathway required for cell survival. However, this value is strongly dependent on the macromere concentrations, while the hydrogels with 12% macromere concentration (2DC12) significantly enhanced the oxygen permeability value (1.16-fold). Moreover, after two weeks of culture, rat MSCs (rMSCs) encapsulated in Alg-GO hydrogels expressed troponin T (TNT) and GATA4 markers. Noticeably, the 2DC12 hydrogels enhance rMSCs differentiation markers (1.30-times for TNT and 1.21-times for GATA4). Overall, our findings indicate that tuning the hydrogel compositions regulates the fate of encapsulated rMSCs within hydrogels. These outcomes may promote the advancement of new multifunctional platforms that consider the spatial and transient guidelines of undifferentiated cell destiny and capacity even after transplantation for heart tissue regeneration.

Management of Inflammatory Root Resorption of Maxillary Central Incisors following Traumatic Avulsion.

Background: Avulsion is among the most severe types of dental trauma, which often occurs at young ages and can compromise the long-term prognosis of the traumatized tooth. Case Report. Herein, we report replantation of two avulsed teeth. Our patient was an 11-year-old boy with two avulsed maxillary central incisors due to a bicycle fall 2 months earlier. The patient was referred to us after rigid splinting of his teeth by a surgeon. Long-term calcium hydroxide (CH) therapy was performed for the patient, and after healing of periodontal ligament (PDL), apexification was performed for both teeth followed by root canal therapy. During the 2-year follow-up, both teeth were functional and had no radiographic or clinical evidence of resorption or ankylosis. Conclusion: The reported case highlights the favorably high tissue healing potential following severe dental trauma, given that appropriate treatment is performed. Correct endodontic management can guarantee the long-term prognosis of teeth following severe dental trauma.

Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers.

Dendritic cells (DCs) are considered as a subset of mononuclear phagocytes that composed of multiple subsets with distinct phenotypic features. DCs play crucial roles in the initiation and modulation of immune responses to both allo- and auto-antigens during pathogenic settings, encompassing infectious diseases, cancer, autoimmunity, transplantation, as well as vaccination. DCs play a role in preventing autoimmunity via inducing tolerance to self-antigens. This review focus on the most common subsets of DCs in human. Owing to the low frequencies of DC cells in blood and tissues and also the lack of specific DC markers, studies of DCs have been greatly hindered. Human DCs arise by a dedicated pathway of lympho-myeloid hematopoiesis and give rise into specialized subtypes under the influence of transcription factors that are specific for each linage. In humans, the classification of DCs has been generally separated into the blood and cutaneous subsets, mainly because these parts are more comfortable to examine in humans.

Association of KIR gene polymorphisms with Type 1 Diabetes: a meta-analysis.

PURPOSE: Type 1 Diabetes (T1D) is a T cell-mediated disease, in which autoimmune destruction of insulin-producing ß-cells in pancreatic islets occurs. In recent decades, the role of Killer cell immunoglobulin-like receptor (KIR) gene polymorphisms in susceptibility to T1D has been demonstrated in an increased number of studies. Nonetheless, inconsistency has been observed in the results of performed association studies. To comprehensively clarify the association among KIR gene polymorphisms and the risk of T1D, this meta-analysis on the previously published association studies was carried out via incorporating multiple research. METHODS: No publication has been recorded from Nov 2017 until July 2020 about the KIR genes and T1D. The PubMed/MEDLINE and Scopus databases were systematically searched up to November 2017 to identify investigations on the impact of the polymorphisms of KIR genes on susceptibility to T1D. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated. Funnel plot and Egger test were used to assess the publication bias. Thirteen qualified published case-control articles were found for evaluation in this meta-analysis. RESULTS: Our results show statistical significance between the genetic variations in the KIR2DL1 (OR = 0.42, 95% CI = 0.23-0.77; P = 0.005), KIR2DL2 (OR = 1.15, 95% CI = 1.00-1.32; P = 0.048), and KIR2DL5 (OR = 0.86, 95% CI = 0.75-0.98; P = 0.03) with susceptibility to T1D. CONCLUSIONS: This meta-analysis study provides reliable evidence that KIR gene polymorphisms may contribute to T1D risk. KIR 2DL1 and 2DL5 genes might be considered as a protective factor for T1D, while 2DL2 seemed to be a susceptibility factor.

PTPN22 Gene Polymorphisms in Pediatric Systemic Lupus Erythematosus.

Objective: Pediatric systemic lupus erythematosus (PSLE) is a heterogeneous autoimmune disorder of unknown origin. PTPN22 gene polymorphisms have been associated with SLE in different populations. We investigated the associations of the rs2476601, rs1217414, rs33996649, rs1276457, and rs1310182 SNPs in the PTPN22 gene with PSLE. Materials and methods: 55 PSLE patients and 93 healthy controls were recruited. SNPs were genotyped by the real-time PCR allelic discrimination method. Results: We found that the PTPN22 polymorphisms rs1310182 A allele (p = 0.01, OR = 1.92 95% CI = 1.16-3.18), and rs1310182 AA genotype with (p < 0.001) and rs12760457 TT (p = 0.046) were associated with PSLE. No significant associations were found between other SNPs and PSLE. Conclusions: The PTPN22 rs1310182 A allele and rs1310182 AA genotype were associated with PSLE and may be a possible genetic marker for susceptibility to PSLE. However, further investigation would be required to elucidate the mechanistic role of this association.

Association of T Helper 1 Cytokine Gene Single Nucleotide Polymorphisms with Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Inflammatory bowel disease (IBD) mostly comprised of Crohn's disease (CD) and ulcerative colitis (UC) is a condition arising from the combined effects of genetic, environmental, and immunological factors. IBD is associated with inflammation and altered cytokine profile. OBJECTIVE: This study was aimed at assessing the association between T helper type 1 (Th1) cytokine polymorphisms (interferon gamma [IFN-γ] +874 A/T, interleukin-12 [IL-12] -1188 A/C, IL-2 -330 G/T, IL-2 +166 G/T) and susceptibility to and clinical features of IBD. METHODS: The study population was composed of 75 IBD patients (40 CD patients and 35 UC patients) and 140 healthy controls. Genotyping was performed using polymerase chain reaction with sequence-specific primers. RESULTS: The A allele of IFN-γ +874 polymorphism was overrepresented in the whole population of patients with IBD (OR 1.63; 95% CI 1.08-2.47; p = 0.020) and as well in the subpopulation of patients with CD (OR 2.14; 95% CI 1.26-3.63; p = 0.004), but not in UC. Multiple pairwise comparisons indicated that genotypes of single nucleotide polymorphisms (SNPs) within the IL-2 and IFN-γ genes are correlated with IBD, CD, and UC, while neither allele nor genotype frequency of th1 IL-12 -1188 polymorphism was associated with IBD, CD, or UC. Haplotype analysis also revealed that the presence of IL-2 -330/+166 TG haplotype versus the remaining haplotypes (GG, TT, and GT) is a protective factor against IBD (OR 0.62; p = 0.046). CONCLUSIONS: The present study reports (for the first time) significant associations between SNPs within the IFN-γ and IL-2 genes and IBD.

Interleukin-4 and Interleukin-10 Gene Polymorphisms in Patients with Inflammatory Bowel Disease.

BACKGROUND: Changes in cytokine expression have been frequently found in patients with inflammatory bowel disease (IBD). Cytokine values outside the normal range may be somewhat related to common polymorphisms within cytokine genes. OBJECTIVE: The present study was designed to investigate the possible association between polymorphisms within Interleukin IL-4 and IL-10 genes and susceptibility to and clinical features of IBD. METHODS: The study population was composed of 140 healthy controls and 75 patients with IBD (40 patients with Crohn's disease (CD) and 35 patients with ulcerative colitis (UC)). Genotyping was performed using polymerase chain reaction with sequence-specific primers. RESULTS: Higher frequencies for the C allele of IL-4-590 polymorphism (P < 0.0001; odds ratio [OR], 5.68; 95% confidence interval [95% CI], 3.28-9.83) and for the T allele of IL-4-1098 polymorphism (P = 0.016; OR, 1.83; 95% CI, 1.11-3.02) were observed in the whole group of IBD patients. The IL-4-590 C allele was also significantly overrepresented when IBD patients were subdivided into CD and UC (P < 0.0001; OR, 5.2-6.28). While the IL-4-1098 T allele was present at higher frequencies in patients with UC (P = 0.05; OR, 1.95), but not in CD (P = 0.09). Multiple pairwise comparisons indicated that genotypes of all polymorphisms investigated within IL-4 gene are correlated with IBD, CD, and UC. Haplotype analysis showed that the IL-4-1098/-590 TC haplotype might predispose individuals to IBD, CD, and UC whereas the IL-4-1098/-590 TT and GC haplotypes have a protective effect. On the contrary, neither allele nor genotype frequencies of IL-10 polymorphisms (IL-10-1082 A > G, IL-10-592 A > C, and IL-10-819 T > C) were associated with IBD, CD, or UC. CONCLUSIONS: The present study suggests that IL-4 polymorphisms might play a role in susceptibility to IBD and its major subtypes in the Iranian population.

Association of the Single Nucleotide Polymorphisms of the Genes Encoding IL-2 and IFN-γ With Febrile Seizure.

Inflammatory elements and genetics have major roles in febrile seizures (FS) pathogenesis. Seventy patients were enrolled and compared with 139 controls. The allele and genotype frequency of the IL-2 gene at -330 and +166 positions and the IFN-γ at +874 position were determined. A significant positive association with GG genotype at position -330 in the patient group was found (P=0.003). Further, a positive association was detected in simple and complex FS groups at the same position (P=0.03, P=0.004). IL-2 GT haplotype was significantly more common in the patients compared to controls (P=0.0008). Higher frequency of GT haplotype was detected in simple FS patients in comparison to controls (P=0.0003). Contrary, IL-2 TG haplotype frequency was lower in complex FS group (P=0.005). Overrepresentation of certain alleles, genotypes and haplotypes in IL-2 gene in FS patients could predispose individuals to this disease.

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus.

BACKGROUND: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease. OBJECTIVE: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene. METHODS: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene. RESULTS: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs. CONCLUSIONS: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.

Association of PTPN22 Gene Polymorphisms with Susceptibility to Juvenile Idiopathic Arthritis in Iranian Population.

Juvenile idiopathic arthritis (JIA), the most common cause of chronic arthritis in children, is a complex immune-mediated disease with considerable long-term morbidity and mortality. According to previous studies, PTPN22 gene has been associated with JIA in several populations. In the present study, we attempted to determine the association of PTPN22 single nucleotide polymorphisms (SNPs) with susceptibility to JIA in Iranian population. Using the Real-time PCR allelic discrimination method, samples consisting of 55 unrelated patients and 93 healthy controls were genotyped. Using Fisher exact test or Chi-square test, genotypic and allelic frequencies were estimated. The results of our study indicated a significantly decreased association of rs1310182 (OR = 0.59, 95% CI = 0.36 -0.97, p = 0.037) with JIA. This association may indicate a protective role for rs1310182 SNP against JIA. More research would be needed to elucidate the mechanistic role of this association.

APRIL gene polymorphism and serum sAPRIL levels in children with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-factor autoimmune disorder with diverse clinical manifestations and unclear pathogenesis. Genetic components play important roles in the incidence and development of SLE. Among these, APRIL as a cytokine has roles in the stimulation and antibody production in B cells. APRIL was hypothesized to be associated with SLE. The aim of this study was to assess the involvement of the APRIL gene in SLE susceptibility in Iranian patients. A single-nucleotide polymorphism (SNP) for rs11552708 of APRIL gene was analyzed by real-time PCR in 60 SLE Iranian children and 64 healthy controls. DNA samples of patients and healthy controls were extracted from peripheral blood leukocytes by phenol-chloroform. Serum samples obtained from 45 children with SLE and 45 healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). The G/G genotype (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.22-2.07; P = 0.68) and G allele (OR 0.81, 95% CI 0.25-2.56; P = 0.89) frequencies of polymorphism at codon 67 (67G) do not differ significantly in the SLE patients compared with those in the healthy controls. The serum APRIL levels in the SLE patients (mean ± SD = 29.27 ng/ml ± 20.77, range from 0 to 55.33 ng/ml) were significantly higher than those in the healthy controls (P = 0.02). Our results demonstrated that rs11552708 of the APRIL gene is not associated with SLE susceptibility in Iranian children. Likewise, these findings suggest that APRIL antagonist could be a potential therapeutic target to control SLE in children.

Expression of T Helper 17 and Regulatory T Cell Cytokines and Molecules in Glomerulonephritis Class IV Systemic Lupus Erythematosus.

INTRODUCTION: Lupus nephritis is a serious organ involvement with unknown etiology, and glomerulonephritis class IV is one of the most severe forms of the disease which correlates with poor prognosis and death. Immunological abnormalities are implicated in the expression of lupus nephritis. In this study, we examined some T helper 17 and regulatory T-related cytokines and molecules in systemic lupus erythematosus patients with glomerulonephritis class IV. MATERIALS AND METHODS: The study group comprised of 20 glomerulonephritis class IV SLE patients and 20 sex- and age-matched SLE patients without kidney involvement as control group. Blood samples was collected from each participant, lymphocytes were isolated, and RNA was extracted from lymphocytes. Then cDNA was synthesized using reverse transcription enzyme, and finally using specific primers and probes, the expression levels of forkhead box P3 (Foxp3), transforming growth factor (TGF)-ß, interferon (IFN)-γ, interleukin (IL)-6, and IL-17 genes were analyzed by real-time polymerase chain reaction based on the TaqMan method. RESULTS: The expression levels of IL-6, IL-17, IFN-γ, and Foxp3 genes were significantly higher in SLE patients with glomerulonephritis class IV than those with non-nephritis SLE. However, the expression of TGF-ß was not significantly different between the SLE patients with and without glomerulonephritis class IV involvement. CONCLUSIONS: According to our results, it seems that in class IV glomerulonephritis patients, increased Foxp3-producing regulatory T cells has an imperfect capacity to control the pathogenic IL-17- and IFN-γ-producing cells.