STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods—A case–control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results—The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions—In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.

Background . Neuropeptide Y (NPY) is a sympathetic neurotransmitter with effects on the regulation of inflammatory cells. The role of NPY on autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is not completely understood. Therefore, we evaluate if NPY levels are markers of disease activity in RA and if there is a correlation between NPY levels and tumor necrosis factor‐alpha (TNF‐ α ), leptin, and interleukin 6 (IL‐6) levels. Methods . Cross‐sectional design, including 108 women with RA. We assessed disease activity by DAS28‐ESR (considering active disease a score of ≥2.6). Serum NPY levels and anti‐CCP2 antibody, TNF‐ α , IL‐6, and leptin levels were quantified (ELISA). Results . Sixty‐eight RA had an active disease (RA‐active), and 40 were in remission (RA‐remission). RA‐active patients had higher NPY levels vs. RA‐remission (22.8 ± 13.6 vs. 17.8 ± 10.3; p = 0.04). NPY levels correlated with increased TNF‐ α levels ( r = 0.32, p = 0.001). Leptin or IL‐6 did not correlate with NPY levels. In the logistic regression analysis, NPY increased the risk of disease activity (OR: 1.04, 95% CI 1.006‐1.09, and p = 0.03). Conclusion . Higher NPY levels are an independent marker of disease activity in RA. This study encourages the quantification of NPY levels as a surrogate marker for RA‐active. Future studies evaluating the role of NPY levels interacting with other proinflammatory cytokines are required.

Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls ( ). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression ( ). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls ( ). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 ( ). In subanalysis, patients with genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls ( ). No increased risk was observed in genotypes of CYP27B1 rs10877012 ( ). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. Methods: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. Results: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13–21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54–93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79–88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. Conclusion: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.

The Receptor Activator Nuclear of κB Ligand (RANKL) plays an important function in immune responses, activating osteoclast cells and unchanged bone resorption, which in turn leads to bone erosion and inflammation. Genetic variants in the promoter region of the RANKL gene could lead to a higher risk of rheumatoid arthritis (RA). Objective: To assess the association of rs9533155 (-693C>G) and rs9533156 (-643T>C) genetic variants with RA risk. Methods: A case–control study was carried out. A total of 94 patients with RA (RA group) and 134 subjects without any rheumatologic disease (control group) were included. Genetic DNA was extracted from peripheral white blood cells (leukocytes). Genetic variant rs9533155 (-693C>G) was screened by an approach based on Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), while rs9533156 (-643T>C) was screened using quantitative polymerase chain reaction (qPCR) with TaqMan probes. RANKL serum levels were measured by ELISA. Results: For rs9533155 (-693C>G), the polymorphic homozygous genotype frequencies (CC) were higher in the RA group (p = 0.006). Individuals carrying the risk genotype presented higher levels of serum RANKL. Carriers of the polymorphic homozygous genotype in the dominant model (CC vs. CG + GG) had an increased risk of developing RA (OR: 1.8, 95% CI 1.04 to 3.1). No association between rs9533156 (-643T>C) and the haplotypes with RA risk was observed. Conclusion: The rs9533155 (-693C>G) genetic variant exhibits a potential role in RA risk. The studied population had no association with the rs9533156 (-643T>C) genetic variant.