The functional TNFAIP3 rs2230926T/G (Phe127Cys) variant confers risk to systemic lupus erythematosus in a Latin American population.

TNFAIP3 is a classical systemic lupus erythematosus (SLE)-associated risk locus identified by genome-wide association studies (GWASs) and replicated by candidate gene association studies primarily in Caucasians and Asians. However, in Latin American populations, its role on SLE susceptibility is not known. We conducted a case-control study to evaluate whether the TNFAIP3 rs2230926T/G (Phe127Cys) variant is associated with risk of developing SLE in a cohort of Mexican patients. The TNFAIP3 rs2230926T/G variant was analyzed in 561 patients with SLE and 499 control subjects, using TaqMan probes. We found that the G allele was associated with susceptibility to SLE under the allelic (OR 2.09, p = 0.005) and genotypic (OR 2.14, p = 0.004) models. In conclusion, our results show that TNFAIP3 rs2230926T/G is a risk factor for the development of SLE in the Mexican population.

No association of eight TNFAIP3 single nucleotide variants to rheumatoid arthritis in Mexicans.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin with many associated genetic traits, including genes related to the control of inflammation. The A20 protein, encoded by the TNFAIP3 gene, is a negative regulator of NF-kB mediated inflammation. Several single nucleotide variants (SNVs) of TNFAIP3 are associated with susceptibility to RA in different ethnic groups, none of which has been evaluated in Mexican patients. OBJECTIVE: To examine the possible association of eight TNFAIP3 SNVs in Mexican patients with RA. MATERIALS: We studied 471 patients with RA and 500 controls, as well as eight TNFAIP3 SNVs: including, rs10499194C/T, rs6920220G/A, and rs2230926T/G, which have been associated with RA in European or Asian patients, in addition to rs373421182G/C, rs139054966T/G, rs5029924C/T, rs59693083A/G and rs61593413T/A, not previously examined in RA. All SNVs were evaluated by means of an allelic discrimination assay using TaqMan probes. RESULTS: The allelic and genotypic frequencies of all SNVs examined were similar between cases and controls, and none of them was associated with RA under the allelic, codominant, dominant, and recessive models, as well as in haplotype combinations. CONCLUSION: Our data indicate that TNFAIP3 SNVs evaluated herein are not risk factors for RA in Mexican subjects.

TNFSF4 is a risk factor for rheumatoid arthritis but not for primary Sjögren's syndrome in the Mexican population.

PURPOSE: Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are autoimmune diseases (ADs) characterized by joint damage and involvement of the salivary glands, respectively. ADs share some susceptibility loci, such as TNFSF4, which is a classical susceptibility gene associated with systemic lupus erythematosus, but its role in RA and pSS is not yet clear. Thus, the aim of this study was to determine whether three TNFSFS4 polymorphisms are associated with RA and pSS. METHODS: Our case-control study included 500 controls, 459 patients with RA, and 210 patients with pSS from Mexico. TNFSF4 single nucleotide polymorphisms (SNPs) rs1234315C/T, rs2205960G/T, and rs704840T/G were genotyped using TaqMan probes and discrimination allelic assay. RESULTS: The three TNFSF4 SNPs were associated with susceptibility to RA (rs1234315C/T: odds ratio [OR] 1.4, p = 0.01; rs2205960G/T: OR 1.23, p = 0.03; rs704840T/G: OR 1.24, p = 0.02). An association between TNFSF4 rs1234315C/T and pSS was also observed (OR 1.28, p = 0.04), however, after Bonferroni correction, this association was lost. CONCLUSION: Our data suggest that TNFSF4 could be a risk factor in RA but not pSS in a Mexican population.

A Novel Technique for the Evaluation and Interpretation of Elastography in Salivary Gland Involvement in Primary Sjögren Syndrome.

Ultrasound (US) of major salivary glands (MSG) evaluates echogenicity, border features and vascularization, with elastography, it can detect tissue elasticity and glandular fibrosis, related to inflammation in Primary Sjögren's syndrome (pSS). This study aimed to develop a novel technique by pixel analysis for evaluation and interpretation of elastography in MSG in pSS. A cross-sectional and observational multicenter study was conducted. The US of MSG performed in orthogonal planes in grayscale, Doppler, and shear-wave elastography. For elastography images of each gland were analyzed with the open-source program ImageJ to perform a pixel analysis. Statistical analysis was performed with the IBM-SPSS v25 program. Fifty-nine women with a mean age of 57.69 (23-83) years were recruited; pSS mean duration of 87 (5-275) months, and 12 healthy women without sicca symptoms as a control group with a mean age of 50.67 (42-60) years. Intragroup analysis showed p-values >0.05 between sicca symptoms, ocular/dryness tests, biopsy, US, and pixel analysis; correlation between Hocevar and pixel analysis was not found (rho < 0.1, p >0.5). MSG anatomical size was 41.7 ± 28.2 mm vs. 67.6 ± 8.8 mm (p ≤ 0.0001); unstimulated whole saliva flow rate was 0.80 ± 0.80 ml/5 min vs. 1.85 ± 1.27 ml/5 min (p = 0.016). The elastography values (absolute number of pixels) were 572.38 ± 99.21 vs. 539.69 ± 93.12 (p = 0.290). A cut-off point risk for pSS identified with less than 54% of red pixels in the global MSG mass [OR of 3.8 95% CI (1.01-15.00)]. Pixel analysis is a new tool that could lead to a better understanding of the MSG chronic inflammatory process in pSS.

BLK and BANK1 variants and interactions are associated with susceptibility for primary Sjögren's syndrome and with some clinical features.

BLK and BANK1 in primary Sjögren's syndrome (pSS) have scarcely been evaluated and the results are inconclusive. The aim of our study was to determine whether single nucleotide variants (SNVs) located within BLK or BANK1 are associated with susceptibility, clinical and serological features, and smoking in pSS. BLK rs13277113A/G, BANK1 rs10516487G/A and rs3733197G/A were genotyped in 203 cases and 424 controls using a TaqMan® SNP genotyping assay. The BLK rs13277113A allele showed association with pSS under the allelic (OR 1.35, p = 0.02), and recessive (OR 1.83, p = 0.003) model, while, BANK1 rs3733197G/A showed association under the dominant model (OR 2.90, p = 0.043). Interactions between BANK1 and BLK genotypes also showed association (OR 2.36, p < 0.0001). In addition, BLK rs13277113A/G was associated with protection against arthritis and BANK1 rs10516487G/A with both arthritis and keratoconjunctivitis sicca, meanwhile, BANK1 rs3733197G/A was associated with smoking in patients with pSS. This is the first study to describe an association between BLK and susceptibility to pSS in a Latin-American population. Our data also shows a first evidence of association between interactions of BLK and BANK1 in pSS, and association of BLK and BANK1with arthritis, keratoconjunctivitis sicca and smoking in patients with pSS.

TNFSF4 is a risk factor to systemic lupus erythematosus in a Latin American population.

OBJECTIVE: The aim of this study was to examine the association of three TNFSF4 single nucleotide variants (SNVs) with systemic lupus erythematosus (SLE) susceptibility in Mexican patients. METHODS: Genotypes of the TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G SNVs were determined using a TaqMan assay. In our study, we included 395 patients with SLE and 500 controls. RESULTS: Our information shows a significant difference in the allelic and genotypic frequency of the three TNFSF4 SNVs between cases and controls. Thus, our data showed an association between TNFSF4 rs1234315T/C (T vs. C, OR 1.40, p = 0.00087), rs2205960G/T (G vs. T, OR 1.32, p = 0.0037), and rs704840T/G (T vs. G, OR 1.41, p = 0.0003) and SLE susceptibility in Mexican subjects. Besides, we conducted a meta-analysis to determine the role of TNFSF4 rs2205960G/T and SLE susceptibility; our results showed that this variant is a risk factor for SLE in Latin Americans and Asians. CONCLUSION: Our results show that TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G are risk factors to SLE in Mexicans. This is the first study to document an association between TNFSF4 rs704840T/G and SLE in a Latin American population. In addition, our meta-analysis showed that TNFSF4 rs2205960G/T is a risk factor for Asians and Latin Americans. Key Point • The TNFSF4 rs1234315T/C, rs2205960G/T, and rs704849T/G SNVs are risk factors to SLE in patients from Mexico.

The VEGFA -1154G/A polymorphism is associated with reduced risk of rheumatoid arthritis but not with systemic lupus erythematosus in Mexican women.

BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention. Thus, the present study aimed to determine whether the VEGFA -2578C/A, -1154G/A and -634G/C polymorphisms confer risk or were associated with reduced risk of RA or SLE in a Mexican population. METHODS: The present study included 903 women from Mexico: 405 were patients with RA, 282 had SLE and 216 were healthy individuals. The genotypes were obtained with TaqMan probes. RESULTS: The data obtained in the present study suggest that the VEGFA -2578C/A and -634G/C polymorphisms are not risk factors for RA or SLE; however, VEGFA -1154G/A was associated with reduced risk in women with RA (odds ratio = 0.6, pc  = 0.0051) but not with SLE (odds ratio = 0.7, pc  = 0.13). CONCLUSIONS: The present study is the first to document an association between VEGFA -1154G/A and reduced risk in women with RA but not with SLE.

Tumor necrosis factor gene polymorphisms are associated with systemic lupus erythematosus susceptibility or lupus nephritis in Mexican patients.

The TNF -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms have consistently been associated with systemic lupus erythematosus (SLE) in several populations; however, these findings have not been verified in all populations. Here, we aimed to examine whether the TNF -238G/A, -308G/A, -376G/A (rs1800750), and -1031T/C (rs1799964) polymorphisms confer SLE or lupus nephritis (LN) susceptibility in a Mexican population. Our study included 442 patients with SLE and 495 controls. For genotyping, we used the TaqMan 5' allele discrimination assay. The TNF -238G/A and -1031T/C polymorphisms were associated with SLE susceptibility (odds ratio (OR) 2.1, p = 0.0005 and OR 1.4, p = 0.003, respectively). Gender stratification showed a strong association between TNF -238G/A and SLE in women (OR 2.2, p = 0.00006), while TNF -1031T/C had an OR of 1.5 (p = 0.007). With regard to the TNF -376G/A polymorphism, this also showed association with SLE susceptibility (OR 1.95, p = 0.036) and LN (OR 3.5, p = 0.01). In conclusion, our study provides the first demonstration of association between the TNF -376G/A polymorphism and SLE and LN susceptibility. In addition, our study is the second documenting an association of TNF -1031T/C with SLE susceptibility. We also observed a strong association between TNF -238G/A and SLE susceptibility. The TNF 308G/A polymorphism was not associated with SLE or LN.

Tumor necrosis factor (TNF) and TNFR1 polymorphisms are not risk factors for rheumatoid arthritis in a Mexican population.

Tumor necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Different genetic variants including the TNF -308G/A polymorphism are associated with RA susceptibility. However, these findings have not been replicated in all populations. The aim of this study was to determine whether the TNF -1031T/C (rs1799964), -376G/A (rs1800750), -308G/A (rs1800629) -238G/A (rs361525), and TNFR1 -609G/T polymorphisms are associated with RA susceptibility in a sample of Mexican patients. Our study included 499 patients with RA and 492 healthy controls. The genotypes of the TNF polymorphisms were obtained using TaqMan assay. The genotype and allele frequencies of the TNF -1031T/C, -376G/A, -308G/A, -238G/A, and TNFR1 -609G/T polymorphisms were similar among RA cases versus healthy controls, and no association with RA susceptibility was identified. Our results suggest that the TNF -1031T/C, -376G/A, -308G/A, -238G/A, and TNFR1 -609G/T polymorphisms are not associated with RA susceptibility in a sample of Mexican patients.

[Tuberculous rheumatism "Poncet's disease". Case report]. / Reumatismo tuberculoso "enfermedad de Poncet". Reporte de caso.

BACKGROUND: Deaths due to tuberculosis have reached 2.5 million cases per year worldwide. Poncet's disease is an infrequent form of tuberculosis characterised by a clinical picture of polyarthritis. CLINICAL CASE: A 24-year-old male presented with morning stiffness, arthralgias, bilateral symmetric arthritis of the proximal interphalangeal joints, wrists, knees, ankles, and shoulders, and adenomegalies at the cervical, submandibular, left supraclavicular, axillary and inguinal levels, without fever. Laboratory results were as follows: ESR 44mm/h, C-reactive protein 4.35, normal levels of complement C3 and C4, negative rheumatoid factor and anticyclic citrullinated peptide antibodies, positive antinuclear antibodies with fine speckled pattern (1:320) and cytoplasm (1:160) pattern and negative anti-Smith, -double-stranded DNA, Sjogren's syndrome-antigen A and Sjogren's syndrome-antigen B. Histological report of cervical node tissue revealed granulomatous lesions compatible with tuberculosis. Rheumatoid arthritis and systemic lupus erythematosus were ruled out. Anti-tuberculosis agents were initiated that resolved the clinical picture. Diagnosis of Poncet's disease was confirmed. CONCLUSION: The differential diagnosis between tuberculosis and autoimmune inflammatory joint diseases is a clinical challenge.