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.

Mechanisms of Immunosuppressive Tumor Evasion: Focus on Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a malignancy with high heterogeneity in its biological features and treatments. Although the overall survival (OS) of patients with ALL has recently improved considerably, owing to the application of conventional chemo-therapeutic agents, approximately 20% of the pediatric cases and 40-50% of the adult patients relapse during and after the treatment period. The potential mechanisms that cause relapse involve clonal evolution, innate and acquired chemoresistance, and the ability of ALL cells to escape the immune-suppressive tumor response. Currently, immunotherapy in combination with conventional treatment is used to enhance the immune response against tumor cells, thereby significantly improving the OS in patients with ALL. Therefore, understanding the mechanisms of immune evasion by leukemia cells could be useful for developing novel therapeutic strategies.

TLR4 and TLR9 polymorphisms are not associated with either rheumatoid arthritis or systemic lupus erythematosus in Mexican patients.

Toll-like receptor (TLR)-mediated signaling pathways induce a proinflammatory microenvironment to eradicate pathogens. However, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), TLRs can promote chronic inflammation. It has been shown that some TLR4 and TLR9 single nucleotide polymorphisms (SNPs) are risk factors for RA and SLE, but these findings have not been replicated in all populations; thus, results are inconclusive. We evaluated the TLR4 Asp299Gly, Thr399Ile, - 1892G/A SNPs, and the TLR9 Pro545Pro SNP to assess potential associations with RA and SLE in Mexican patients. This study included 474 patients with RA, 283 patients with SLE, and 424 healthy controls. We used a 5' nuclease allelic discrimination assay to genotype individuals for the four TLR4 and TLR9 polymorphisms. We found that the genotype or allelic frequencies of the TLR4 Asp299Gly, Thr399Ile, - 1892G/A, and TLR9 Pro545Pro polymorphisms were similar between patients and controls. We found no association under different genetic models. A haplotype analysis of TLR4 showed no association with either RA or SLE. We found no significant differences in the allelic or genotypic frequencies of TLR4 Asp299Gly, Thr399IIe, - 1892G/A, or TLR9 Pro545Pro between patients and controls. These findings suggested that these variants are not risk factors for RA or SLE in Mexican patients.

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.

Immunization of BALB/c mice with pigeon IgY induces the production of anti-IgG autoantibodies.

The breakdown of immunological tolerance due to the activation of autoreactive B and T cells triggers physiopathological processes. An example of such conditions is the production of IgG autoantibodies specific for the Fc portion of IgG (anti-Fcγ IgG). Previous reports have shown that patients with pigeon-related hypersensitivity pneumonitis exhibit an increase in the serum levels of anti-Fcγ IgG. There is no in vivo model for the study of this condition and the immunological mechanisms of tolerance breakdown associated with sensitization by pigeon antigens are still unknown. In this work, we show that the repeated immunization of BALB/c mice with pigeon IgY during 16-weeks induces the production of anti-Fcγ IgG and keeps their high levels for seven weeks. The late appearance of anti-Fcγ IgG autoantibodies in the plasma is similar to what has been reported in other experimental autoimmune models. With the occurrence of anti-Fcγ IgG, there is a reduction in the proportion of Foxp3 + cells (regulatory T cells, Tregs) within the population of splenic CD4 + CD25 + T cells. Thus, our data showed that the immunization of BALB/c mice with IgY promotes the production of anti-Fcγ IgG along with a decrease in Tregs in the spleen. We propose that immunization of mice with pigeon antigens, like IgY can provide a model to study the immunological mechanisms involved in the development of pigeon-related hypersensitivity pneumonitis.

Clinical comparison of two Mexican coccidioidins.

Coccidioidin, an extract from the saprophytic mycelial form of Coccidioides spp., has been a very useful antigen preparation both for skin and serological tests for coccidioidomycosis. Unfortunately, coccidioidin is not currently available for skin testing in the United States. Coccidioidin has been produced commercially in Mexico by a vaccine and reagents laboratory of the Mexican Federal Government. It also has been produced at the Microbiology Laboratory of the Faculty of Medicine, Universidad Nacional Autónoma de México exclusively as an antigen for research projects. The objective of the study was to compare both coccidioidins in their reactivity and safety when applied in humans. One hundred and eighty-four volunteers were tested; median age was 33 (range 14-82). When the cutoff point is set in 5 mm, 88 subjects (47.8%) had a positive test for the commercial coccidioidin and 76 (41.3%; CI(95%) 0.50, 1.15; P = 0.20) were positive with the research antigen. Seventy-five subjects were positive for both antigens and 96 were negative for both. Fifty-nine subjects (31.3%) reported an adverse reaction after the application of the antigen; they were mostly very mild local reactions. Mexican research coccidioidin is a safe and reliable antigen that can be used for the detection of coccidioidomycosis infection in mammals.