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B cell-activating factor (BAFF) is an essential cytokine in primary Sjogren’s syndrome (pSS) physiopathology. It has been reported that pSS patients develop germinal center-like (GC-like) structures in their minor salivary glands (MSGs). BAFF, BAFF-R, TACI, and BCMA expression was analyzed in MSGs from 29 subjects (nonspecific chronic sialadenitis and focal lymphocytic sialadenitis with the presence [pSS-GC(+)] or absence [pSS-GC(−)] of GC-like structures). Twenty-four percent of patients showed ectopic GC-like structures and a high focus score [p

Psoriasis is a chronic, autoimmune skin disease. In psoriasis, PON1 activity is diminished and peroxidation biomarkers are elevated. The most studied PON1 polymorphisms are rs662 (A G) and rs854560 (A T), which have been associated with the antioxidant activity of PON1, risk of cardiovascular diseases and psoriasis development. The aim of this study, was to determine the association of rs662 (A G) and rs854560 (A T) PON1 polymorphisms with psoriasis susceptibility in Western Mexico population. In this case-control study, we included 104 psoriasis patients and 124 control subjects. The genotyping of polymorphisms rs662 (A G) and rs854560 (A T) of PON1 was carried out by PCR-RFLPs. The lipid profiles were quantified by enzymatic colorimetric method, and PON1 activity was determined by spectrophotometry. The lipid profile levels, except HDL-C and atherogenic index, were higher in patients vs. controls. Patients presented lower paraoxonase and arylesterase activity. The G allele of rs662 (A G) is associated with risk for psoriasis, while the T allele of rs854560 (A T) is associated with low susceptibility to psoriasis. The AG haplotype was more frequent within the patient group (p 0.05). The AA and AG genotypes of rs662 (A G) and TT and AA genotypes of rs854560 (A T) are associated with lower PONase and ARE activity in patients vs. controls. Patients with the G allele of rs662 (G A) and T alleles of rs854560 (A T) show significant differences in the lipid levels in comparison to controls. These results suggest that carriers of G allele of rs662 (A G) present a greater susceptibility to psoriasis.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G

Background Glatiramer acetate (GA) is a drug for Multiple Sclerosis (MS) treatment. However, its administration induces anti-drug antibodies (ADA). This research evaluated the sex differences in humoral response against GA in RR-MS patients Methods We analyzed 69 RR-MS patients, 43 treated with GA and 26 treated with IFN-β. In all cases, the serum concentration of IgG antibodies was determined by UPLC, whereas the levels of IgG subclasses (1–4) of anti-GA antibodies and the concentration of IL-6 were detected by Multiplex and IL-10, and IFN-γ were detected by ELISA. Results The total concentration of IgG antibodies in patients did not differ between treatments, whereas the IgG levels of ADA were higher in male and female patients treated with GA (P ≤ 0.0001). The subclasses of IgG anti-GA antibodies were as follows: IgG4>>IgG3>IgG1>IgG2. Statistical analysis showed differences in the IgG2 (P ≤ 0.01) and IgG4 (P ≤ 0.0001) subclasses by sex in RR-MS patients. Levels of IgG1 subclass in male patients correlated positively with the circulatory levels of IL-6 (rs = 0.587, P ≤ 0.04) and IFN-γ (rs = 0.721, P ≤ 0.001), while IgG2 subclass levels in female patients correlated with serum levels of IFN-γ (rs = 0.628, P ≤ 0.0006). Statistical analysis did not detect correlations between the levels of IgG (1–4) subclasses of anti-GA antibodies and the evaluated clinical parameters. Conclusion This study showed differences in the levels of IgG2 and IgG4 subclasses of ADA between male and female RR-MS patients. Further studies are necessary to take advantage of the clinical potential of this finding.

Background:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction of exocrine glands secondary to lymphocytic infiltration. Lymphoid tyrosine phosphatase (LYP) regulates T and B lymphocyte activation.PTPN22gene encodes LYP; multiple polymorphic variants have been described as genetic risk factor of autoimmune diseases.Objectives:The aim was to analyze thePTPN22rs2488457G>C, rs33996649G>A, and rs2476601C>T genetic variants relationship with the development risk of pSS in the western Mexico population.Methods:One hundred and eighty healthy subjects (HS) and 150 pSS patients, classified according to EULAR 2016 criteria, were included. The genetic variants and mRNA expression were determined through PCR-RFLP and qPCR assays.Results:The frequency of heterozygote rs33996649GA genotype was higher in pSS patients than HS [OR=3.143 (1–10.234), p=0.046], and also, rs33996649GA genotype was associated with high SSDAI score (p=0.01). The pSS patients showed 44-fold more mRNA expression in comparison with HS (p=0.002), and mRNA expression correlates with SSDAI (r2=0.512, p=0.006).Conclusion:The rs33996649G>A genetic variant of thePTPN22gene is associated with increased development risk of pSS in the western Mexican population. The expression mRNA correlates with disease activity in pSS.References:[1]Brito-Zerón, P., Baldini, C., Bootsma, H., Bowman, S. J., Jonsson, R., Mariette, X., Ramos-Casals, M. (2016). Sjögren syndrome.Nature Reviews Disease Primers, 2(July), 1–20.https://doi.org/10.1038/nrdp.2016.47[2]Stanford, S. M., & Bottini, N. (2014). PTPN22: The archetypal non-HLA autoimmunity gene.Nature Reviews Rheumatology,10(10), 602–611.https://doi.org/10.1038/nrrheum.2014.109[3]Chen, Z., Zhang, H., Xia, B., Wang, P., Jiang, T., Song, M., & Wu, J. (2013). Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis.International Journal of Colorectal Disease,28(10), 1351–1358.https://doi.org/10.1007/s00384-013-1671-3[4]Machado-Contreras, J. R., Muñoz-Valle, J. F., Cruz, A., Salazar-Camarena, D. C., Marín- Rosales, M., & Palafox-Sánchez, C. A. (2016b). Distribution of PTPN22 polymorphismsin SLE from western Mexico: correlation with mRNA expression and disease activity.Clinical and Experimental Medicine,16(3), 399–406.https://doi.org/10.1007/s10238-015-0359-0Disclosure of Interests:None declared

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

Interleukin 10 (IL-10) is an immunoregulatory cytokine with multiple roles in the immune system. Three single nucleotide polymorphisms at positions -1082 (AG), -819 (CT), and -592 (CA) in the promoter region of the IL10 gene are believed to be associated with different inflammatory, infectious, and autoimmune diseases. These polymorphisms exhibit a strong linkage disequilibrium (LD) and form three principal haplotypes (GCC, ACC, and ATA). The GCC and ATA haplotypes have been associated with high and low levels of IL-10 production, respectively. The aim of this study was to establish the allele and haplotype frequencies of the IL10 polymorphisms in Mestizos from western Mexico. SNPs were analyzed in 340 healthy unrelated Mestizos from western Mexico by polymerase chain reaction-restriction fragment length polymorphism. The studied population presented significant differences, in the distribution of IL10 polymorphisms, from the Asian, African, and European populations. We also observed a strong LD within -1082 AG, -819 CT, and -592 CA (100% pc = 7.735 x 10

Objective: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28null T-cells, both present in synovial membrane of RA. Therefore we evaluated the associations of KIR genes with RA. Methods: 16 KIR genes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences in KIR genotypes and gene frequencies were assessed using the X2 test. Results: Gene frequency of KIR2DL3 was lower in RA than in HS (p = 0.0019), whereas KIR2DL2 and KIR2DS2 were higher in RA than HS (p = 0.0004 and p = 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p = 0.0001, p = 0.0208 and p = 0.0300, respectively). Conclusions: The presence of KIR2DL2, KIR2DS2 and absence of KIR2DL3 are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest that KIRs can be involved in RA susceptibility.

Objective: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Results: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p = 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p = 0.016), was found. Conclusion: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.

We describe a family with a 7-year-old proband case diagnosed with systemic lupus erythematosus (SLE) plus secondary anti-phospholipid syndrome (APS) as well as two affected paternal aunts. We compared the frequency of these polymorphisms with healthy controls.To evaluate the mode of inheritance in this familial case of APS and SLE and the possible association of plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G and PAI-2 Ser(413)/Cys polymorphisms. To compare the genotype frequency of these polymorphisms with the results found in a Mexican Mestizo population.PAI-1 -675 4G/5G and PAI-2 Ser(413)/Cys were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique using Bsl I and Mwo I on four generations of the family studied. PAI-2 Ser(413)/Cys polymorphism was also determined in 50 healthy individuals of Mexican Mestizo origin.The family pedigree demonstrated that this family did not follow a Mendelian inheritance pattern. When the PAI-2 Ser(413)/Cys polymorphism was examined, we found that 60% (3/5) of the relatives homozygous to Ser(413)/Ser were affected with SLE and/or APS (p = 0.027). The proband case was 4G/5G genotype for the PAI-1 -675 4G/5G polymorphism. No differences between healthy controls of the Mexican Mestizo population and the family studied for the PAI-2 Ser(413)/Cys polymorphism or PAI-1 -675 4G/5G polymorphisms were found.Our data indicate that this family did not follow the Mendelian inheritance pattern. The Ser(413)/Ser genotype demonstrated in 60% of the affected members (3/5) of this family might increase the risk for autoimmune syndromes such as APS or SLE.

To determine IL-1 beta, TNF alpha, IL-6, IL-4, IL-10, MMP-1, MMP-3 and MMP-13 expression by freshly isolated peripheral blood (PBMC) and synovial fluid mononuclear cells (SFMC) in early, never-treated (ENT-RA) and non-acute, treated rheumatoid arthritis (NAT-RA) patients. To elucidate whether excessive or inadequate interleukin (IL) and metalloprotease (MMP) expression is influenced by the disease duration.Fourteen RA patients, 7 with early RA (1 year of evolution) never treated with corticosteroids or disease-modifying antirheumatic drugs, and 7 patients with non-acute RA (2 years of evolution) treated with disease-modifying antirheumatic drugs, were studied by ELISA and quantitative and semiquantitative RT-PCR. A group of 14 healthy subjects matched for sex and age was included.No statistically significant difference in the protein or transcript levels for the cytokines of interest was found between the ENT-RA and NAT-RA groups. The cytokine mRNA expression by freshly isolated PBMC and SFMC in both groups was as follows: IL-1 betaTNF alphaIL-10IL-6, with no mRNA IL-4 expression. In contrast, cytokine serum levels in ENT-RA and NAT-RA patients were detected in inverse order as follows: IL-6IL-10, while IL-1 beta, TNF alpha and IL-4 were undetectable. MMP-3 mRNA expression by the PBMC of NAT-RA patients was statistically different to that in ENT-RA patients. Similar levels of mRNA expression of MMP-1, MMP-3 and MMP-13 by the PBMC and SFMC in both RA groups were observed.A close equilibrium between MMP and pro/anti-inflammatory cytokine production is observed in ENT-RA and NAT-RA patients. This balance is apparently not influenced by the length of the disease. Highly sensitive methods such as quantitative RT-PCR and ELISA, and even studying freshly isolated MC, showed sustained cytokine secretion at the local level (synovial fluid/SFMC) and scarce translation at the peripheral level (serum/PBMC). Expression of MMP mRNA needs to be further evaluated in order to know whether their peripheral expression reflects their local activity in RA patients.