Seroprevalencia de enfermedad celiaca en pacientes con infertilidad. Un estudio de casos y controles / Celiac disease seroprevalence in patients with infertility. A case-control study

Resumen Antecedentes: Aunque los pacientes con enfermedad celiaca (EC) tienen en su mayoría manifestaciones digestivas, algunos pueden presentarlas de índole extraintestinal (atípicas), como anemia crónica, ataxia y trastornos de la fertilidad. Objetivo: Determinar la prevalencia de anticuerpos relacionados con EC en mujeres mexicanas con trastornos de la fertilidad. Material y métodos: Estudio de casos y controles de mujeres que acudieron a valoración por trastornos de la fertilidad en un centro especializado. Se cuantificó h-tTG IgA, gliadina IgA II y gliadina IgG II; los títulos > 30 UI fueron considerados como positivos. Resultados: Se incluyeron 171 casos y 171 controles; 137 pacientes (80.1 %) tuvieron infertilidad y 34 (19.9 %), esterilidad. Ocho pacientes (4.6 %, IC 95 % = 2.3-8.9) tuvieron al menos un marcador positivo para EC comparadas con una mujer del grupo control (0.5 %, IC 95 % = 0.01-3, p = 0.04, razón de momios = 8.3). Seis de las ocho pacientes presentaron infertilidad inexplicable. Conclusiones: Hasta 4.6 % de las mujeres con infertilidad presentó al menos un marcador positivo para EC. Al igual que en otras partes del mundo, podría recomendarse el escrutinio para EC en mujeres con infertilidad, en especial en quienes padecen infertilidad inexplicable.

Abstract Background: Although most patients with celiac disease (CD) have digestive manifestations, in some of them they may be of extraintestinal (atypical) nature, such as chronic anemia, ataxia, and fertility disorders. Objective: To determine the prevalence of CD-related antibodies in Mexican women with fertility disorders. Material and methods: Case-control study of women who attended evaluation for fertility disorders in a specialized center. h-tTG-IgA, gliadin IgA II and gliadin IgG II were quantified; titers > 30 IU were considered positive. Results: One-hundred and seventy-one cases and 171 controls were included; 137 patients (80.1%) had infertility, and 34 (19.9%), sterility. Eight patients (4.6%, 95% CI = 2.3-8.9) had at least one positive marker for CD in comparison with one woman in the control group (0.5%, 95% CI = 0.01-3, p = 0.04, odds ratio = 8.3). Six of the eight patients had unexplained infertility. Conclusions: Up to 4.6% of women with infertility had at least one positive marker for CD. As in other parts of the world, screening for CD could be recommended in women with infertility, especially in those with unexplained infertility.

The Prevalence of Anti-Zein Antibodies: A Comparative Study between Celiac Disease and Irritable Bowel Syndrome.

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. In contrast, irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting the large intestine, without an autoimmune component. Here, we evaluated the prevalence of IgA and IgG antibodies to maize zeins (AZA) in patients with CD and IBS. Using an in-house ELISA assay, the IgA and IgG anti-zein antibodies in the serum of 37 newly diagnosed CD (16 biopsy proved and 21 serological diagnosis) and 375 IBS patients or 302 healthy control (HC) subjects were measured. Elevated levels of IgA AZA were found in CD patients compared with IBS patients (p < 0.01) and HC (p < 0.05). CD patients had the highest prevalence (35.1%), followed by IBS (4.3%) and HCs (2.3%) (p < 0.0001). IgG AZA antibodies were not found in any CD patients, IBS patients, or HC subjects. A significant positive correlation was found between IgA AZA with IgA anti-gliadin (AGA, r = 0.34, p < 0.01) and IgA anti-deaminated gliadin peptides (DGP, r = 0.42, p < 0.001) in the celiac disease group. Taken together, our results show for the first time a higher prevalence of AZA IgA antibodies in newly diagnosed CD patients than in IBS patients, confirming a biased immune response to other gliadin-related prolamins such as maize zeins in genetically susceptible individuals.

Optimization of Zika virus envelope protein production for ELISA and correlation of antibody titers with virus neutralization in Mexican patients from an arbovirus endemic region.

BACKGROUND: Zika virus (ZIKV) has become a global threat with immediate need for accurate diagnostics, efficacious vaccines and therapeutics. Several ZIKV envelope (Env)-based vaccines have been developed recently. However, many commercially available ZIKV Env are based on the African lineage and produced in insect cells. Here, we sought to produce Asian-lineage ZIKV Env in mammalian cells for research and clinical applications. METHODS: We designed various gene expression constructs to optimize the production of ZIKV using prM-Env and full or C-terminal truncations of Env; with or without a rat CD4 fusion partner to allow large-scale production of soluble protein in mammalian HEK293 cells. Protein expression was verified by mass spectrometry and western-blot with a pan-flavivirus antibody, a ZIKV Env monoclonal antibody and with immune sera from adenoviral (ChAdOx1) ZIKV Env-vaccinated mice. The resulting Env-CD4 was used as a coating reagent for immunoassay (ELISA) using both mouse and human seropositive sera. RESULTS: Replacement of the C-terminus transmembrane Env domain by a rat CD4 and addition of prM supported optimal expression and secretion of Env. Binding between the antigens and the antibodies was similar to binding when using commercially available ZIKV Env reagents. Furthermore, antibodies from ZIKV patients bound ZIKV Env-CD4 in ELISA assays, whereas sera from healthy blood donors yielded minimal OD background. The serological outcomes of this assay correlated also with ZIKV neutralisation capacity in vitro. CONCLUSIONS: Results obtained from this study indicate the potential of the Asian-lineage Zika Env-CD4 and Env proteins in ELISA assays to monitor humoral immune responses in upcoming clinical trials as well as a sero-diagnostic tool in ZIKV infection.

First Insights into the Gut Microbiota of Mexican Patients with Celiac Disease and Non-Celiac Gluten Sensitivity.

Gluten-related disorders (GRDs) are common chronic enteropathies and increasing evidence suggests an involvement of the gut microbiota. We examined the gut microbiota in Mexican people afflicted with GRDs. Ultra-high-throughput 16S marker sequencing was used to deeply describe the duodenal and fecal microbiota of patients with celiac disease (CD, n = 6), non-celiac gluten sensitivity (NCGS, n = 12), and healthy subjects (n = 12) from our local area. Additionally, we also investigated the changes in gut microbiota after four weeks on a gluten-free diet (GFD) in a subset of patients from whom paired samples were available. Despite a high inter-individual variability, significant differences in various microbial populations were identified. The linear discriminant analysis (LDA) effect size (LEfSe) method revealed that the genus Actinobacillus and the family Ruminococcaceae were higher in the duodenal and fecal microbiota of NCGS patients, respectively, while Novispirillum was higher in the duodenum of CD patients (p < 0.05, LDA score > 3.5). Interestingly, paired samples from NCGS patients showed a significant difference in duodenal Pseudomonas between the baseline period (median: 1.3%; min/max: 0.47⁻6.8%) and the period after four weeks on GFD (14.8%; 2.3⁻38.5%, p < 0.01, Wilcoxon signed-rank test). These results encourage more research on GRDs in México.

Elevated circulating levels of IL-21 and IL-22 define a cytokine signature profile in type 2 autoimmune hepatitis patients.

UNLABELLED:  Background and aims. Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver in which the immunological mechanisms involved in tissue destruction and/or repair are still unclear. Different pro-inflammatory cytokines have been shown to play a determinant role in AIH pathogenesis. Here, we aim to compare the circulating levels of pro- and anti-inflammatory cytokines such as IL-6, TNF-?, IL-17A/F, IL-21, IL-22, IL-23, and IL-10 in patients with type 2 AIH compared to patients with type 1 AIH and healthy controls (HC). Fourty-six Mexican patients with AIH were recruited in our study. Patients were classified as type 1 or 2 AIH based on immune serological markers. Fourty-four serum samples from healthy individuals were included as controls. Serum cytokine levels were determined by ELISA technique. RESULTS: Compared to healthy controls, serum levels of IL-17F, IL-21, IL-23, IL-10, IL-6, and TNF-?, but not IL-17A and IL-22, were significantly increased in AIH patients. When patients were grouped by aminotransferase activity, a biomarker of active disease, a positive correlation between serum IL-17F and alanine transaminase (rs: 0.4739; P = 0.0009) and aspartate transaminase (rs: 0.4984; P = 0.0004) levels was found. A cytokine signature profile associated with type 2 AIH was characterized by high serum IL-21 (type 1 AIH: 0.66 pg/mL; type 2 AIH: 331.1 pg/mL; P = 0.0042) and IL-22 (type 1 AIH: 0.1 pg/mL; type 2 AIH: 55.26 pg/mL; P = 0.0028) levels. CONCLUSIONS: We show for the first time, differential regulation of certain pro-inflammatory cytokines associated with disease progression and AIH type in Mexican patients.

Recombinant Listeria monocytogenes expressing a cell wall-associated listeriolysin O is weakly virulent but immunogenic.

Listeriolysin O (LLO) is an essential virulence factor for the gram-positive bacterium Listeria monocytogenes. Our goal was to determine if altering the topology of LLO would alter the virulence and toxicity of L. monocytogenes in vivo. A recombinant strain was generated that expressed a surface-associated LLO (sLLO) variant secreted at 40-fold-lower levels than the wild type. In culture, the sLLO strain grew in macrophages, translocated to the cytosol, and induced cell death. However, the sLLO strain showed decreased infectivity, reduced lymphocyte apoptosis, and decreased virulence despite a normal in vitro phenotype. Thus, the topology of LLO in L. monocytogenes was a factor in the pathogenesis of the infection and points to a role of LLO secretion during in vivo infection. The sLLO strain was cleared by severe combined immunodeficient (SCID) mice. Despite the attenuation of virulence, the sLLO strain was immunogenic and capable of eliciting protective T-cell responses.