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Ines Matia-Garcia,1 Eduardo Vadillo,2 Rosana Pelayo,3 José F Muñoz-Valle,4 Mariel García-Chagollán,4 Jaqueline Loaeza-Loaeza,1 Amalia Vences-Velázquez,1 Lorenzo Salgado-Goytia,1 Samuel García-Arellano,4 Isela Parra-Rojas1 1Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México; 2Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional, Instituto Mexicano del Seguro Social, Ciudad de México, México; 3Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Atlixco, Puebla, México; 4Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, MéxicoCorrespondence: Isela Parra-RojasLaboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo, Guerrero, 39090, MéxicoTel +52 7474719310Email iprojas@yahoo.comPurpose: We aim to identify Th1 and Th2 cell clusters in young subjects, including their clinical and metabolic characteristics and the Th1/Th2 balance.Patients and Methods: A total of 100 participants were included. The frequencies of Th1 and Th2 cells in peripheral blood were determined by flow cytometry. Serum C-reactive protein was measured using a turbidimetric assay, and insulin levels were quantified with an enzyme-linked immunosorbent assay. Circulating cytokine levels were analyzed using a multiplex system.Results: A cluster analysis was performed to determine the Th1/Th2 balance in a group of young people, and 3 clusters were formed with the following characteristics: 1) subjects with a higher prevalence of hyperglycemia (38%), dyslipidemia (38– 75%), and insulin resistance (50%), as well as a higher percentage of Th1 cells and Th1/Th2 ratio, including elevated IFN-ɣ levels; 2) subjects with a lower prevalence of hyperglycemia (23%) and insulin resistance (15.4%), but a higher prevalence of dyslipidemia (8– 85%) with a predominance of Th2 cells, and lower Th1/Th2 ratio; 3) subjects with a lower prevalence of hyperglycemia (6%), insulin resistance (41%), and dyslipidemia (10– 63%), as well as a balance of Th1 and Th2 cells and lower Th1/Th2 ratio, including low IFN-ɣ levels. Positive correlations between Th1 cells with IFN-γ, IL-12, and IL-1β and between Th2 cells with IFN-γ, IL-2, and IL-4 were found (p < 0.05). A significant increase in Th1 cells was observed in the presence of hyperglycemia and high LDL-C levels, as well as increased Th2 cells in the absence of abdominal obesity and high blood pressure, including low HDL-C levels. The Th1/Th2 ratio was higher in the group with high cardiometabolic risk (p = 0.03).Conclusion: Th1/Th2 balance is related to metabolic abnormalities that may occur in young population, and thus the timely identification of different phenotypes may help predict an increased cardiometabolic risk.Keywords: Th1 cells, Th2 cells, hyperglycemia, dyslipidemias, IFN-ɣ levels

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis, two processes associated with transforming growth factor β (TGF-β) functions. In the present study, we investigated the expression of TGF-β isoforms in serum and the skin distribution of TGF-β and two receptors (TGF-βR1 and TGF-βR2) and their relationship with some clinical, inflammatory, autoimmune (autoantibodies), and vascular (platelets) biomarkers in SSc patients. A total of 56 SSc patients and 120 control subjects (CS) were included. The serum levels of TGF-β isoforms were quantified by immunoassay with magnetic microspheres, and the skin biopsies were processed by immunohistochemistry. The soluble levels of the three active TGF-β isoforms were lower in SSc patients than in CS (p 0.0001). However, sTGF-β1 and sTGF-β3 levels were positively correlated with C-reactive protein levels in SSc patients. Additionally, sTGF-β2 and sTGF-β3 levels were positively correlated with the number of platelets in SSc patients. In skin biopsies, TGF-β1, TGF-βR1, and TGF-βR2 expression levels were higher in SSc patients than CS. In conclusion, this is the first study showing a joint decrease of the 3 active TGF-β isoforms in SSc patients. However, TGF-β1, TGF-βR1, and TGF-βR2 are possibly increased in clinically involved skin. Therefore, it is likely that a distinct role is played by TGF-β at the local (skin lesions) and systemic levels in SSc patients.

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. Methodology: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. Results: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p

Background Macrophage inhibitory factor (MIF) is a pro‐inflammatory cytokine secreted by several cells, including those in the immune system and the skin. The MIF gene contains the SNP ‐173 G> C and STR ‐794 CATT5‐8 polymorphisms in the promoter region capable of affecting its activity. Our objective was to investigate the MIF polymorphisms as a risk factor for plaque psoriasis (PP) in the Mexican population. Methods We genotyped both MIF polymorphism (rs5844572 and rs755622) in 224 PP patients with a clinical and histopathological diagnosis and 232 control subjects (CS) by the PCR‐RFLP method. MIF serum levels were determined by an ELISA kit. Results We found significant differences in the genotypic and allelic frequencies for the MIF ‐173 G>C polymorphism; carriers of the GC genotype (OR 1.51, 95% CI 1.026–2.228, p = 0.03) and the C allele (OR 1.34, 95% CI 1.005–1.807, p = 0.04) had higher odds to present with PP. Moreover, the 6C haplotype was associated with PP risk (OR 2.10, 95% CI 1.22–3.69, p, Summary of key results from this study. (1) “Linkage disequilibrium was identified between ‐173 G>C and STR‐794 CATT5‐8 polymorphisms (D′ value = 0.62, r2 = 0.17, p

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity.This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI).The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices.Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points • IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. • RF, anti-CCP, and anti-MCV had higher levels in early than established RA. • IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. • Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.

Background Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. Methods Ninety‐nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K‐mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal‐Wallis test and the Bonferroni test. Results Higher IFN‐γ, IL‐17F, IL‐21, IL‐23, IL‐4, and IL‐31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. Conclusion Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach., Principal component analysis of 14 cytokines was realized to determine the cytokine groups in primary Sjögren´s syndrome patients. The mild group was characterized by less severity of the disease with low cytokine levels and fewer clinical parameters; the moderate group included patients with intermediate severity, presented higher cytokine levels than the mild group but less than severe group. Patients of the severe group showed higher severity, higher cytokine levels, and clinical parameters.

This study aimed to summarize the epidemiological and clinical characteristics of COVID-19 from Western Mexico people during 2020. A retrospective analysis from an electronic database of people visiting a sentinel center for molecular SARS-CoV-2 confirmatory diagnosis by RT-PCR from April to December 2020 was carried out for epidemiological and clinical description of COVID-19. Out of 23,211 patients evaluated, 6918 (29.8%) were confirmed for SARS-CoV-2 infection (mean age 38.5 ± 13.99), mostly females (53.8%). Comorbidities, such as diabetes (34.7%), obesity (31.15%), and hypertension (31.8%), presented an increased odds OR = 1.27, CI = 1.14–1.41, OR = 1.08, CI = 1.01–1.16, and OR = 1.09, CI = 0.99–1.19, respectively, for viral-infection. Moreover, fever, headache, and dry cough were the most frequent symptoms. No infection difference among sex was found. Those patients &gt, 60 years old were prone to COVID-19 severity (OR = 3.59, CI = 2.10–6.14), evaluated by the number of manifested symptoms, increasing with age. In conclusion, a high SARS-CoV-2 prevalence was found in Western Mexico. Comorbidities were frequent in infected people, nevertheless, no association with disease outcomes was observed, in contrast with the highest disease severity risk found in older patients, however, continuous monitoring should be carried since comorbidities have been reported as aggravating factors. This study can help the health officials for the elaboration of planning efforts of the disease management and others in the future.

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_89∗G, PADI4_90∗T and PADI4_92∗G gene polymorphisms were associated with RA susceptibility (OR=1.34, p=0.04; OR=1.35, p=0.03; OR=1.34, p=0.04; respectively). The GTG haplotype was also significantly associated with RA (OR=2.27 95%CI=1.18-4.41; p=0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.

It has been accepted that satiety‐ and appetite‐stimulating hormones play a role in the regulation of food intake and body composition during and after the lactation stage. Therefore, the purpose was to demonstrate that serum appetite‐regulating hormones in infants differ according to anthropometric indicators and type of feeding. In a nonrandom cohort study, 169 mother–newborn dyads whose pregnancy and birth were attended at the Hospital Civil de Guadalajara were enrolled. According to the type of feeding, infants were classified as full breastfeeding (FBF), partial breastfeeding (PBF), and infants receiving human milk substitutes (HMS). Serum concentrations of ghrelin (pg/ml), leptin (ng/ml), peptide YY (pg/ml), and glucagon‐like peptide‐1 (GLP‐1) (pM) were measured. Anthropometric measurements including weight, length, cephalic, arm circumference, tricipital, and subscapular skinfolds were obtained. Weight/age, weight/height, height/age, and BMI Z‐score indexes were estimated. We performed one‐way ANOVA, unpaired Student's t test, post hoc Tukey test, and Pearson correlation tests. The ANOVA comparison of the three feeding types showed significant differences in most anthropometric indicators (z‐scores), especially between infants receiving FBF versus HMS and particularly on indicators of adiposity; no differences were observed in length and cephalic circumference z‐scores at 8th and 16th weeks. Further, significant correlations were found between most of the adiposity indicators with ghrelin, leptin, and GLP‐1, especially in infants who received FBF. There were differences in anthropometric and body composition parameters among infants receiving FBF, PBF, and HMS. There were significant correlations between body composition indicators with ghrelin, leptin, and GLP‐1 mainly in infants receiving FBF., This was a comparative and correlational analysis of a nonrandom cohort study of 169 infant/mother dyads. We measured appetite‐regulating hormones and performed anthropometry related to growth and body composition; the analysis was carried out according to the type of feeding. We found differences in body composition according to the type of feeding and correlations of anthropometric indicators with ghrelin, leptin, and GLP‐1, especially in infants who received full breastfeeding.

Introduction : Prolactin (PRL) is a 23-kDa protein that can be synthesized and secreted by pituitary and extrapituitary tissues such as immune cells due to its expression being regulated by two independent promoter regions. The promoter which is responsible for extrapituitary expression contains the single nucleotide polymorphism (SNP) –1149 G/T previously associated with autoimmune diseases in various populations. This study evaluates the relationship of PRL –1149 G/T polymorphism with PRL serum levels and clinical characteristics in systemic lupus erythematosus (SLE) patients from western Mexico. Material and methods: One hundred and sixty-three SLE patients classified according to the 1982 American College of Rheumatology (ACR) SLE classification criteria and 326 unrelated control subjects (CS), both from western Mexico, were included. The PRL –1149 G/T polymorphism was genotyped using the polymorphism was performed by the polymerase chain reaction restriction fragment length polymorphism technique, and both PRL serum levels and autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA). Results : We found an association between the PRL –1149 TT genotype and SLE according to the recessive genetic model (OR = 2.26, 95% CI: 1.01–5.08, p = 0.04). The TT genotype was associated with anti-RNP antibodies (p = 0.04) and with higher scores of the Mex-SLEDAI (p = 0.02). Moreover, SLE patients showed elevated PRL serum levels (12.4 ng/ml; p < 0.01), and this condition was associated with renal activity and the presence of anti-RNP antibodies. Conclusions : PRL –1149 TT genotype is associated with susceptibility to SLE in a Mexican-Mestizo population, and high PRL serum levels are associated with anti-RNP antibodies and renal activity.

The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.

espanolObjetivo: evaluar la relacion entre la concentracion de suero y la leche materna y la concentracion de grelina y leptina en leche materna en madres lactantes segun el tipo de alimentacion. Metodos: diseno de cohorte realizado en 131 diadas madre-lactante que ingresaron en una sala de puerperio fisiologico. Variables independientes: tipo de alimentacion, lactancia materna completa (LMC, 56,5%) y lactancia materna parcial (LMP, 43,5%). Variables dependientes: concentracion serica de grelina total (pg/ml) y leptina (ng/ml), leche humana pre-tetada y pos-tetada a las ocho y 16 semanas. Se utilizaron pruebas no pareadas t de Student, U de Mann-Whitney, correlacion de Pearson, coeficiente de determinacion y regresion linear. Resultados: la concentracion de grelina y leptina en leche humana pre-tetada fue mayor que en leche humana pos-tetada en ambos grupos a las ocho y 16 semanas. La concentracion de grelina y leptina fue mayor en suero que en leche humana en ambos grupos; estos valores mostraron una correlacion lineal directa y significativa con la excepcion de la grelina en el grupo de LMC. La concentracion serica de leptina en las madres explico el 32% de la varianza de su concentracion en leche humana en LMC y el 13% en madres en LMP. Conclusion: el gradiente de leche humana pre-tetada/pos-tetada sugiere un mecanismo de regulacion e ingestion de leche. La concentracion de grelina y leptina fue mayor en suero que en leche humana y los coeficientes de determinacion sugieren una transferencia de suero-leche, ademas de una regulacion de la sintesis por la glandula mamaria, el tejido adiposo u otros organos. EnglishObjective: we assessed the relationship between serum and human foremilk and hindmilk concentrations of ghrelin and leptin in nursing mothers according to the type of feeding. Methods: this cohort design was carried out on 131 mother-newborn dyads admitted to a physiological puerperium ward. The independent variables were the type of feeding, full breastfeeding (FBF, 56.5%) and partial breastfeeding (PBF, 43.5%). The dependent variables were the concentration of total ghrelin (pg/ml) and leptin (ng/ml) in serum, foremilk and hindmilk at eight and 16 weeks. Fasting blood samples were obtained from the nursing mothers at four months for serum assays. Unpaired Student’s t-test, Mann-Whitney U test, Pearson’s correlation tests, coefficient of determination and linear regression were used. Results: the concentration of ghrelin and leptin in hindmilk was higher than that of foremilk in both groups at eight and 16 weeks. The concentration of ghrelin and leptin was higher in serum than in foremilk in both groups. These values showed a direct and significant linear correlation with the exception of ghrelin in the FBF group. The serum concentration of leptin in mothers explained 32% of the variance of its concentration in foremilk in the FBF and 13% in the PBF groups. Conclusion: the hindmilk/foremilk gradient suggests an intake regulating mechanism during the fed. The concentration of ghrelin and leptin was higher in the serum than in foremilk and its correlation and determination coefficients could suggest plasma-milk transfer in addition to synthesis regulation by the mammary gland, adipose tissue or other organs.

Satiety and appetite‐stimulating hormones play a role in the regulation of food intake. Breastfed infants may have a different profile of serum appetite‐regulating hormones than formula‐fed infants. We propose to demonstrate that the serum concentration of appetite regulatory hormones differs according to the type of feeding and that there is a correlation between the serum concentrations of these hormones in mothers and in infants at 4 months of age. In a cross‐sectional analysis, 167 mother–newborn dyads at the Hospital Civil de Guadalajara were enrolled: 74 full breastfeeding (FBF), 56 partial breastfeeding (PBF), and 37 receiving human milk substitutes (HMS). Serum levels of ghrelin (pg/ml), leptin (ng/ml), peptide YY (pg/ml), and glucagon‐like peptide‐1 (GLP‐1) (pM) were measured. We performed one‐way analysis of variance, unpaired Student t test, post hoc Tukey test, and Pearson correlation. The total sample at 16 weeks postpartum included 167 dyads. The mean age was 16 ± 1 weeks. The concentrations of GLP‐1 (pM) and peptide YY (pg/ml) were higher in the FBF group (42.6 and 442.9) than in the HMS group (35.2 and 401.9), respectively, p = 0.046 and p = 0.056. And, the FBF group had higher correlation coefficients of ghrelin (r = 0.411 vs. 0.165), GLP‐1 (r = 0.576 vs. 0.407), and peptide YY (r = 0.218 vs. 0.067), respectively, than the HMS group. The concentrations of GLP‐1 and peptide YY were higher in the FBF group when compared with the HMS group. Mother–infant dyads fed by FBF had more significant direct correlations of appetite‐regulating hormones than those who received HMS.

Periodontitis is modulated by a complex dysbiotic microbiota, these species stimulate upward the production of pro-inflammatory cytokines such as TNF-α, which, in turn, upregulates the production of bone resorption molecules. Enzymes such as MMP-8 and 9 have been associated with the destructive disease. This study evaluated the composition of periodontal microbiota with the checkerboard hybridization technique and its correlation with TNF-α, MMP-8, and MMP-9 evaluated with ELISA, of 80 patients (45 healthy, and 35 with chronic periodontitis). The frequency of the 18 species evaluated was higher in patients with bone loss compared with control group. TNF-α in gingival crevicular fluid was significantly higher in bone loss group (p

Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms − 794 CATT5–8 (rs5844572) and − 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the − 794 CATT5–8 and − 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc. A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively. An association between the − 794 CATT7 and − 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p

BACKGROUND Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS). METHODS The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit. RESULTS The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p

Background Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important role in the development and pathogenesis of rheumatoid arthritis (RA). MIF promotes the expression of cytokines related to RA development, as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-17. Two polymorphisms in the promoter of the MIF gene have been associated with increased production of protein and it has been shown that TNF-α is involved in the regulation of MIF mRNA expression and protein secretion in a dose-dependent manner. Objectives To evaluate the effect of MIF gene haplotypes on rhTNF-α and rhMIF response in peripheral blood mononuclear cells (PBMC) of RA patients Methods Genotyping was performed for MIF gene haplotypes in 230 RA patients. Cell culture of PBMC from two patients per homozygous haplotype (5G, 6G and 7C) was performed and stimulated with rhTNF-α and rhMIF. Cytokine levels were analyzed by a microsphere-based ELISA method (Bio-Plex® MAGPIX™). Results rhTNF-α and rhMIF-induced IL-6, IL-17A and IL-17F secretion in PBMC of RA patients. We observed that PBMC extracted from patients with MIF 7C haplotypes stimulated with rhTNF showed higher secretion of IL-17A and IL-17F than patients with 5G and 6G haplotypes. IL-6 production with rhMIF stimulation was more pronounced in the 5G haplotype group than 6G or 7C haplotype groups. Conclusions rhTNF-α and rhMIF promote differential secretion of IL-6, IL-17A and IL-17F according to MIF haplotypes presence. IL-17A and IL-17F secretion of stimulated PBMC with rhTNF-α are higher in patients with 7C haplotype than non-7C haplotypes. Furthermore, IL-6 levels are higher in PBMC from patients with 5G haplotype stimulated with MIF than non-5G haplotypes. References McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis - shaping the immunological landscape. Nat Rev Rheumatol 2016;12(1):63–68. Llamas-Covarrubias MA, Valle Y, Navarro-Hernandez RE, Guzman-Guzman IP, Ramirez-Duenas MG, Rangel-Villalobos H, Estrada-Chavez C, Munoz-Valle JF. Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course. Rheumatol Int 2012;32(8):2307–2311. Stojanovic I, Cvjeticanin T, Lazaroski S, Stosic-Grujicic S, Miljkovic D. Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells. Immunology. 2009;126(1):74–83. Gregersen PK y Bucala R. Macrophage migration inhibitory factor, MIF alleles, and the genetics of inflammatory disorders: incorporating disease outcome into the definition of phenotype. Arthritis Rheum. 2003;48(5):1171–6. Xiong C1, Huang B, Cun Y, Aghdasi BG, Zhou Y. Migration inhibitory factor enhances inflammation via CD74 in cartilage end plates with Modic type 1 changes on MRI. Clin Orthop Relat Res. 2014;472(6):1943–54. Acknowledgements This study was supported by funding from the National Council of Science and Technology (CONACYT) Grant #161749 assigned to JFMV. Disclosure of Interest None declared

Interleukin 10 (IL-10) is an immunomodulatory cytokinethat plays a central rolein the pathogenesis of autoimmune diseases. Different studies consistently show increased IL-10 serum levels in rheumatoid arthritis (RA) and it appears to be caused by genetic variants. Three polymorphisms situated at positions -1082, -819 and -592 of IL10 gene and its major haplotypes have been associated with regulating IL10 promoter activity. In this study, we evaluated whether IL10 haplotypes are associated with mRNA expression and IL-10 serum levels as well as susceptibility to RA in a Western Mexican population. A total of 240 RA patients and 240 control subjects (CS) were included. Genotyping of IL10 polymorphisms was performed by PCR and PCR-RFLP, respectively. IL10 mRNA expression was determined by real-time PCR and IL-10 serum levels were measured using an ELISA kit. IL10 mRNA expression was 50-fold higher in RA patients than CS (p

We analyzed the relationship of −794CATT5–8and −173 G>CMIFpolymorphisms with mRNA and soluble MIF in young obese subjects. A total of 250 young subjects, 150 normal-weight and 100 obese subjects, were recruited in the study. Genotyping of −794CATT5–8and −173 G>CMIFpolymorphisms was performed by PCR and PCR-RFLP, respectively. MIF mRNA expression was determined by real-time PCR and serum MIF levels were measured using an ELISA kit. For bothMIFpromoter polymorphisms, no significant differences in the genotype and allele frequencies between groups were observed. MIF mRNA expression was slightly higher in obese subjects than in normal-weight subjects (1.38-fold), while soluble MIF levels did not show differences between groups. In addition, we found an increase in MIF mRNA expression in carriers of the 6,6 and C/C genotypes and the 6G haplotype of the −794CATT5–8and −173 G>CMIFpolymorphisms, although it was not significant. In conclusion, this study found no relationship between obesity andMIFgene promoter polymorphisms with MIF mRNA expression in young obese subjects.