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Objective: To evaluate the efficacy and safety of telitacicept in SLE patients specifically with hematological involvement., Method: A total of 22 patients with SLE and hematological involvement were included in this study. These patients received telitacicept in addition to standard therapy. We compared their demographic characteristics, clinical manifestations, and laboratory indicators before and after the administration of telitacicept., Results: A total of 22 patients received telitacicept treatment for a median duration of 10.4 months (ranging from 6 to 19 months). Following telitacicept therapy, significant improvements were observed in various parameters compared to baseline. Specifically, white blood cell count increased from (3.98 ± 1.80) 10 9 /L to (6.70 ± 2.47) 10 9 /L, (P = 0.002), hemoglobin levels increased from (100 ± 19) g/L to (125 ± 22) g/L, (P < 0.001), and platelet count increased from (83 ± 60) 10 9 /L to (161 ± 81) 10 9 /L, (P = 0.004). SLE Disease Activity Index (SLEDAI) scores decreased from 12(5,15) to 0(0,4), (P < 0.001). Additionally, C3 and C4 levels showed improvement. Telitacicept treatment also resulted in a significant reduction in serum IgG levels and daily prednisone dosage. Only one adverse event (4.5%) was reported during the treatment, which was a urinary tract infection., Conclusion: The combination of telitacicept and standard treatment demonstrated significant improvements in anemia, as well as increased leukocyte and platelet levels in patients with SLE and hematological involvement. Importantly, the observed adverse events were manageable and controllable. Key Points • Telitacicept effectively improves anemia, clinical outcomes, and increases leukocyte and platelet counts. • Treatment with telitacicept leads to decreased levels of lgG, IgA, anti-dsDNA, and SLEDAI scores, while serum complement C3 and C4 returned to normal. • During the follow-up period there were observed changes in individual parameters, clinical symptoms, and organ involvement, all without significant adverse events., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: The present study aimed to examine the effects of cDMARD and bDMARD therapy on both gene expressions and protein levels of TNF-α, IL-6, IL-10 and fatty acid levels in patients with RA. Method: Plasma TNF-α, IL-6, and IL-10 levels were examined by the ELISA method, while TNF-α, IL-6, and IL-10 gene expression levels were examined by RT-qPCR, and fatty acid levels were examined by GC/MS. Results: IL-10 gene expression levels significantly increased in RA patients receiving cDMARD treatment compared to those of the control group. Also, eicosadienoic acid, myristoleic acid and capric acid levels were significantly lower in the patient groups compared to those in the control group. Conclusion: The drugs used in the treatment of RA had no effect on the fatty acid levels whereas had effects on the mRNA and protein levels of the target cytokines. Key Points • There are some studies investigating inflammatory cytokines in rheumatoid arthritis but no study includes fatty acid levels besides the cytokines. Therefore, this study has an important contribution for original articles because of including fatty acid levels besides the cytokines on rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. Methodology: This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). Results: The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. Conclusions: Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points • IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. • RF, anti-CCP, and anti-MCV had higher levels in early than established RA. • IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. • Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15. [ABSTRACT FROM AUTHOR]

Introduction: Prolactin (PRL) is a sex hormone with immunomodulatory properties, and it is associated with the clinical activity of rheumatoid arthritis (RA). The -1149G>T polymorphism at the prolactin (PRL) gene has been associated with autoimmune diseases, but its functional effect is unclear. Objective: To analyze the association of the PRL -1149G>T polymorphism with disease susceptibility, mRNA, and protein expression of PRL in RA patients from Southern Mexico. Methods: We included 300 RA patients and 300 control subjects (CS). Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, the PRL mRNA expression was determined by real-time PCR, and PRL serum levels were measured by enzyme-linked immunosorbent assay. Results: Applying genetic models of inheritance (dominant, recessive, and additive), we found an association between the T allele and decreased RA susceptibility (OR = 0.55, 95% CI 0.35–0.87, p = 0.009; OR = 0.09, 95% CI 0.012–0.76, p = 0.011; OR = 0.49, 95% CI 0.32–0.76, p = 0.001, respectively). RA patients had higher mRNA expression and soluble levels of PRL than CS (p < 0.05). The PRL serum levels were similar in RA and CS according to genotypes. However, in CS, carriers of GT and TT genotypes showed lower PRL mRNA expression than GG genotype carriers (7.1-fold and 20-fold respectively, p = 0.006). Conclusions: This study demonstrated that the PRL -1149T allele is a genetic marker of decrease risk to RA in population from Southern Mexico, and it is associated with low PRL mRNA. Key Points: • PRL -1149T allele is a marker of decreased RA susceptibility in population from southern Mexico. • PRL -1149TT genotype is associated with low PRL mRNA expression. • RA patients have higher mRNA expression and soluble levels of PRL than healthy subjects. • PRL serum levels are higher in those RA patients with < 2 years of disease evolution. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms − 794 CATT5–8 (rs5844572) and − 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the − 794 CATT5–8 and − 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc. Materials and methods: A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively. Results: An association between the − 794 CATT7 and − 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p < 0.05). Also, the 7C haplotype was associated with increased MIF mRNA expression (p = 0.03) in SSc. In addition, an increase of IL-1β and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles. Conclusion: The MIF 7C haplotype is a susceptibility marker for SSc in the southern Mexican population and is associated with MIF mRNA expression. Moreover, there is a positive correlation between MIF serum levels and Th1 and Th17 inflammatory response in SSc. [ABSTRACT FROM AUTHOR]

This study aimed to explore whether interleukin-10 polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). Studies that have analyzed the associations of the interleukin-10-1082G>A, -592C>A, and -819C>T polymorphisms with RA were searched for in PubMed and EMBASE. Sensitivity and cumulative analyses were conducted to measure the robustness of our findings. Egger’s linear regression and Begg’s funnel plots were performed to analyze publication bias. The source of heterogeneity was analyzed by subgroup analysis and meta-regression. This meta-analysis involved 2661 RA patients and 3249 controls in 16 studies. There were significant associations with RA in the AG vs AA model (OR = 0.79, 95% CI = 0.67-0.93, P < 0.01) and the AG + GG vs AA model (OR = 0.80, 95% CI = 0.69-0.93, P < 0.01) for the interleukin-10-1082G>A polymorphism, in the TC vs TT model (OR = 0.61, 95% CI = 0.44-0.84, P < 0.01) and the CC vs TT model (OR = 0.64, 95% CI = 0.46-0.89, P < 0.01) for the interleukin-10-819C>T polymorphism, and in the AC vs AA model (OR = 0.73, 95% CI = 0.56-0.96, P = 0.03) and the AC + CC vs AA model (OR = 0.68, 95% CI = 0.47-0.98, P = 0.04) for the interleukin-10-592C>A polymorphism. Meta-regression revealed that the genotyping method was a major cause of heterogeneity in the AC vs AA model and the AC + CC vs AA model for the interleukin-10-592C>A polymorphism. This meta-analysis showed the interleukin-10-1082G>A, -592C>A, and -819C>T polymorphisms are correlated with the susceptibility to RA. Meta-regression indicated that the genotyping method is a major driver of heterogeneity in the relationship between the interleukin-10-592C>A polymorphism and RA. [ABSTRACT FROM AUTHOR]

Interleukin-10 (IL-10), one of the anti-inflammatory cytokines, plays a major role in the pathogenesis of Henoch-Schönlein purpura (HSP). In present study, we investigated the association between genetic variation in IL-10 gene and susceptibility to HSP in a Chinese childhood population. Considering the overlapping clinical manifestations during the course of disease, the relation between IL-10 gene polymorphisms and HSP clinical heterogeneity was also assessed. We analyzed three IL-10 tag single nucleotide polymorphisms (SNPs; rs3021094, rs3790622, and rs1800872) using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method in 182 patients with HSP and 202 healthy controls. For the frequency of alleles, genotypes, and haplotypes of IL-10 SNPs, no significant differences were observed between HSP patients and controls. In addition, we did not find any association of IL-10 gene polymorphisms with the clinical manifestations of HSP. Our results suggest that genetic variation in IL-10 gene is unlikely to confer susceptibility to HSP in Chinese children. [ABSTRACT FROM AUTHOR]

The antibody against peptidylarginine deiminase (PAD) 4 is a biomarker that might be helpful in the diagnosis of rheumatoid arthritis (RA). We aim to estimate the diagnostic value of anti-PAD4 antibody for RA by meta-analysis. We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for studies published in any languages in March 1, 2017 that evaluated the diagnostic accuracy of the anti-PAD4 antibody for the diagnosis of RA. The articles that detected the anti-PAD4 antibody by enzyme-linked immunosorbent assay (ELISA) and used healthy donors or patients without arthritis or arthralgia as controls were included for meta-analysis. The articles were assessed by Quality Assessment of Diagnostic Accuracy Studies tool. A bivariate mixed-effects model was used to summarize the diagnostic indexes from eight eligible studies. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-PAD4 antibody were 38% (95% CI 30.0-46.0%), 96% (95% CI 93.0-98.0%), 8.96 (95% CI 5.00-16.05), and 0.65 (95% CI 0.57-0.74), respectively. The summary diagnostic odds ratios were 13.74 (95% CI 7.23-26.09), and the area under the summary receiver operator characteristic curve was 86% (95% CI 83-89%). Anti-PAD4 antibody detected by ELISA shows a high value in the diagnosis of RA with high specificity, but relatively low sensitivity. [ABSTRACT FROM AUTHOR]

This study aimed to assess the diagnostic and prognostic value of anti-mutated citrullinated vimentin (MCV) antibodies in very early rheumatoid arthritis (VERA) and in established rheumatoid arthritis (RA). Seventy-one patients with undifferentiated arthritis (UA) of <3 months duration, 141 with established RA, 53 with other rheumatic diseases, and 40 healthy individuals were included in the study. Anti-MCV, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) were determined and hand radiographs were recorded. Patients were assessed prospectively for 2 years, and hand radiographs were repeated. Diagnostic performance of anti-MCV was studied with receiver operating characteristic (ROC) curves and evaluation of sensitivity, specificity, and likelihood ratios. Forty-six percent of UA patients progressed to RA at 2 years. In VERA patients, sensitivity of anti-MCV was 52 %, compared to 44 % of anti-CCP and 37 % of RF, while specificity was 91 %, compared to 91 % of RF and 84 % of anti-CCP. Anti-MCV were detected in 25 % of VERA patients negative for both anti-CCP and RF. In established RA, anti-MCV did not sustain its diagnostic performance. By multivariable analysis, anti-MCV, but not anti-CCP or RF, showed significant correlation with radiographic progression in VERA patients. In established RA, anti-MCV, anti-CCP, and RF were associated with active disease ( p ≤ 0.03) and joint damage ( p ≤ 0.004). By multivariate analysis, the strongest factors for radiographic damage were disease duration ( p = 0.000), HAQ score ( p = 0.000), and RF ( p = 0.002). In conclusion, in patients with very early UA, anti-MCV predict both progression to RA and radiological damage, and therefore, anti-MCV antibody testing may be useful in every day practice. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes ( p values <0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others ( p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients. [ABSTRACT FROM AUTHOR]

The goal of the study was to evaluate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) antibodies in juvenile idiopathic arthritis (JIA) comparing to anti-cyclic citrullinated peptide (anti-CCP). Thirty children with confirmed JIA diagnosis and 20 children as a control group were included into the study. Serum and synovial fluid levels of anti-CCP, anti-MCV, and immunoglobulin M rheumatoid factor (IgM-RF) antibodies have been assessed. Anti-MCV was positive in 11/30 (36.6 %), whereas anti-CCP positivity was found in 12/30 (40 %) children with JIA. Among 11 children with JIA positive for anti-MCV, five (45.5 %) were also positive for anti-CCP and among 18 JIA children negative for anti-CCP, six (33.33 %) were also anti-MCV positive. Six out of 30 JIA children were found to be IgM-RF positive. In general, two out of all those 11 anti-MCV-positive patients demonstrated oligoarthritis and 9/11 had polyarticular type of onset. Anti-MCV serum concentration correlated positively with anti-CCP ( p = 0.004). Almost 60 % of children in early stage of JIA were anti-MCV positive. Levels of anti-CCP antibodies correlated positively with the disease activity ( p = 0.0014) and radiological outcome ( p = 0.00017). In all synovial fluid samples, the concentration of autoantibodies was under the cut-off values. The results of our study indicate that anti-MCV as well as anti-CCP antibodies may be helpful in the diagnosis of JIA, especially in the early course of the disease. Anti-MCV antibodies could identify a group of children with JIA which is negative for anti-CCP antibodies and RF. However, it appears that in JIA, anti-CCP rather than anti-MCV antibodies have impact on radiographic changes. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a complex genetic disease. Human leukocyte antigen (HLA) and non-HLA genes are reportedly associated with an increased risk of RA. The protein tyrosine phosphatase non-receptor 22 gene ( PTPN22), which encodes the lymphoid tyrosine phosphatase (LYP) protein, is one of the best examples of a non-HLA gene associated with a risk for RA in several populations. The functional PTPN22 C1858T (R620W) non-synonymous polymorphism is widely associated with an increased risk for RA in Europeans and non-Europeans. The aim of this study was to determine if the PTPN22 C1858T polymorphism confers susceptibility to RA in a sample of patients from Mexico. This study included 364 RA patients and 387 non-related controls from Central Mexico. Genotyping of the PTPN22 C1858T (rs2476601) polymorphism was performed using allelic discrimination assays with TaqMan probes. The functional PTPN22 C1858T polymorphism was associated with an increased risk for RA in our study population. The CC vs CT genotype in RA patients versus healthy controls had an odds ratio (OR) of 4.17 (95 % CI 1.79-9.74, p = 0.00036), while T allele had an OR of 4.06 (95 % CI 1.75-9.41, p = 0.00043). PTPN22 is a genetic risk factor for developing RA in the Mexican population. [ABSTRACT FROM AUTHOR]