Galectin-9 gene (LGALS9) polymorphisms are associated with rheumatoid arthritis in Brazilian patients.

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and hyperplasia, as well as cartilage and bone destruction. Several proteins are associated with the pathogenesis of the disease. Galectin-9 belongs to the family of lectins that are involved in various biological processes and have anti-inflammatory activity.ObjectiveTo investigate associations between the SNPs of the GAL-9 gene (LGALS9) and serum levels in rheumatoid arthritis patients. We extracted DNA from 356 subjects, 156 RA patients and 200 healthy controls from northeastern Brazil. Three polymorphisms (rs4795835, rs3763959, and rs4239242) in the LGALS9 gene were selected and genotyped using TaqMan SNP genotyping assay. Serum concentrations of galectin-9 were analyzed by ELISA.ResultsThe rs4239242 TT genotype showed a positive association with RA (p = 0.0032, odds ratio = 0.28), and heterozygous TC were prevalent in the control group compared to RA patients (p = 0.0001, odds ratio = 7.99). Galectin-9 serum levels were significantly increased in RA patients compared to the control group (p<0.0001). Patients in remission had high levels of galectin compared to the moderate activity group (p<0.0001). Regarding the Clinical Disease Activity Index (CDAI), patients in remission or low activity presented high levels of galectin when compared to patients in severity (p<0.0001). Patients performing moderate activity had a significant value compared to patients who were in high disease severity (p = 0.0064). Interestingly, the AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients (p = 0.0436). The SNP rs4239242 TT genotype showed a positive association with RA in comparison to the control group. The AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients

Interleukin-18 in Brazilian Rheumatoid Arthritis Patients: Can Leflunomide Reduce It?

Objectives. Rheumatoid arthritis affects about 1% of the world’s population. This is a chronic autoimmune disease. It is predominant in females with progressive joint damage. Immune cells are involved, especially Th1/Th17 lymphocytes and their inflammatory cytokines. These proteins have different functions in the immune system, such as IL-16 is a chemotactic factor; IL-18 can activate NFκB transcription producing inflammatory proteins; IL-31 can activate the JAK/STAT pathway which leads to the production of inflammatory factors in chronic diseases; IL-33 promotes IL-16 secretion which causes lymphocyte recruitment, and IL-32 and IL-34 appear to increase TNF secretion by macrophages activation in AR. The aim of this study was to evaluate serum levels of IL-16, IL-18, IL-31, IL-32, IL-33, and IL-34 and compare them with the severity and treatment of RA patients if there are any correlations. Methods. A total of 140 RA patients and 40 healthy donors were recruited from the Department of Rheumatology at Hospital das Clínicas from the Federal University of Pernambuco. 60 AR patients were naïve for any treatment. Serum cytokine levels were determined using an ELISA kit. Results. Serum IL-16 (p = 0.0491), IL-18 (p < 0.0001), IL-31 (p = 0.0004), and IL-32 (p = 0.0040) levels were significantly increased in RA patients compared with healthy donors. It was observed that patients using leflunomide had the lowest IL-18 levels, close to controls levels (p = 0.0064). Conclusion. IL-16, IL-18, IL-31, and IL-32 are increased in the serum of RA patients. IL-18 is at lower levels in those AR who are taking leflunomide as treatment

Genetic variants in LGALS3 are related to lower galectin-3 serum levels and clinical outcomes in systemic sclerosis patients: A case-control study

Introduction Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene LGALS3 (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis. Objective To investigate associations among LGALS3 single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features. Methods A case-control study with 88 patients and 151 matched controls was performed. LGALS3 variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages. Results The LGALS3 rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 − 3.52); p = .046]. Also, LGALS3 rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels (p = .03) and control group (p = 0.005), as noted by generalized linear model (GLM). The LGALS3 rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes (p = .03); however, in SSc patients, no difference was found. None of the LGALS3 SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed LGALS3 rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels. Conclusion The LGALS3 rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and LGALS3 rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes

Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p = 0.02), digital ulcers (p = 0.02), lung fibrosis (p < 0.0001), positive antitopoisomerase I (p = 0.03), and higher modified Rodnan score (p = 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia

Submitted by Adagilson Silva ([email protected]) on 2017-06-05T13:08:05Z No. of bitstreams: 1 27603703 2016 men-sin.oa.PDF: 1008770 bytes, checksum: 82f0081628ade062bc08ce6be5782a03 (MD5)Approved for entry into archive by Adagilson Silva ([email protected]) on 2017-06-05T13:08:29Z (GMT) No. of bitstreams: 1 27603703 2016 men-sin.oa.PDF: 1008770 bytes, checksum: 82f0081628ade062bc08ce6be5782a03 (MD5)Made available in DSpace on 2017-06-05T13:08:29Z (GMT). No. of bitstreams: 1 27603703 2016 men-sin.oa.PDF: 1008770 bytes, checksum: 82f0081628ade062bc08ce6be5782a03 (MD5) Previous issue date: 2016Programa de Doutorado da Rede Nordeste de Biotecnologia. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT). Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Hematologia e Hemoterapia de Pernambuco (HEMOPE). Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Ciências Biológicas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT). Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Ciências Biológicas. Recife, PE, Brasil.Fundação Hematologia e Hemoterapia de Pernambuco (HEMOPE). Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT). Recife, PE, Brasil.Programa de Doutorado da Rede Nordeste de Biotecnologia. Recife, PE, Brasil / Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Programa de Doutorado da Rede Nordeste de Biotecnologia. Recife, PE, Brasil / Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor

Serum galectin-3 levels associated with <i>LGALS3</i> +191 (A) and +292 (B) genotypes in children with SCA.

<p><i>LGALS3</i> +191: C = reference allele; A = variant allele; <i>LGALS3</i> +292: A = reference allele; C = variant allele; +191 genotypes: CC vs. CA: <i>p <</i>0.0001; CC vs. AA: <i>p <</i>0.0001; CC vs. AA+CA: <i>p</i> <0.0001. +292 genotypes: AA vs. AC: <i>p</i> = 0.1684; AA vs. CC: <i>p</i> = 0.0046; AA vs. CC+AC: <i>p</i> = 0.0136. Mann-Whitney tests.</p

Clinical data of children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p>Clinical data of children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

Serum galectin-3 levels are associated with <i>LGALS3</i> +191 and +292 combined genotypes in children with SCA.

<p>Statistical analysis of <i>LGALS3</i> combined genotype related of galectin-3 levels (high, intermediate and low) in which the serum concentrations in ng/ml were compared using Kruskal-Wallis test. High vs. intermediate: <i>p =</i> 0.1687; high vs. low: <i>p =</i> 0.0002; high vs. intermediate+low: <i>p</i> = 0.0098.</p

<i>LGALS3</i> +191 and +292 combined genotype distribution with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 combined genotype distribution with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p