There is increasing evidence of a close link between inflammation and cancer, and at the core of inflammation there are both pathogen-associated molecular patterns (PAMPs) and danger (or damage)-associated molecular patterns (DAMPs). Microorganisms harbor molecules structurally conserved within groups called PAMPs that are recognized by specific receptors present on immune cells, such as monocytes and dendritic cells (DCs); these are the pattern recognition receptors (PRRs). Activation through different PRRs leads to production of pro-inflammatory cytokines. A robust immune response also requires the presence of endogenous molecules that pose 'danger' to self-tissues and are produced by damaged or stressed cells; these are the DAMPs, which act also as inducers of inflammation. PAMPs and DAMPs are each recognized by a limited set of receptors that in number probably do not exceed 100. PAMPs and DAMPs interact with each other, and a single PRR can bind to a PAMP as well as a DAMP. Within this framework, we propose that PAMPs and DAMPs act in synchrony, modifying the activation threshold of one another. Thus, the range of PAMP-DAMP partnerships defines the course of inflammation, in a predictable manner, in an 'inflammatory code'. The definition of relevant PAMP-DAMP complexes is important for the understanding of inflammatory disorders in general, and of cancer in particular. Here, we review relevant findings that support the notion of a PAMP-DAMP-based inflammatory code, with emphasis on cancer immunology and immunotherapy.
Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT’s adipocytes showed a lower range of size expandability than VAT’s adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT’s larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT’s larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT’s larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.
Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American
Objectives We aimed to determine whether parameters associated with adipose tissue (adipocyte density and the circulating concentrations of markers of adipose tissue pathology) predict cardiovascular risk (CVR) modification after metabolic surgery (MS). Methods We performed a case–control study of patients with morbid obesity who were candidates for MS. CVR was defined using flow-mediated dilation (FMD) and carotid intima media thickness (CIMT), which were measured during the 9 months following MS. Subgroups of CVR reduction were defined using the following cut-offs: CIMT 10% and/or a two-fold increase in FMD. Results We studied 40 patients with morbid obesity (mean age 44.5 years, 75% women, mean body mass index 46.4 kg/m2) and high prevalences of the metabolically unhealthy obesity phenotype, hypertension, and diabetes mellitus. A significant reduction in CVR was associated with lower vascular endothelial growth factor-A concentration (6.20 vs. 1.59 pg/mL, respectively), low adipocyte density in visceral adipose tissue (100 vs. 80 cells/field), low infiltration with CD68+ cells (18 vs. 8 cells/field) and higher concentrations of lipid peroxidation markers and malondialdehyde (313.7 vs. 405.7 ng/mL). Conclusion The characteristics of adipose tissue and the circulating concentrations of markers of adipose pathology might represent useful predictors of the reduction in CVR following MS. Clinical trial registration number: NCT0356198 ( https://clinicaltrials.gov )
Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population.
Background. Leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli Mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. Thus, in this case-control study, we evaluated the possible association between the IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs and susceptibility to leprosy disease in Mexican population. Methods. Seventy-five leprosy patients and sixty-nine control subjects were included. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique. Results. We found nonsignificant differences in genotype and allele frequencies related to IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs in MB as well as subclinical forms of leprosy disease versus healthy individuals. Conclusions. Since the sample size is not large enough, it is difficult to sustain an association of susceptibility to leprosy with genotypes or allele frequencies of IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780), suggesting that IL-17 polymorphisms have no significant role in the genetic susceptibility to development of this disease in the Mexican Mestizo population.
Background Multiple factors are implicated in the etiology and pathogenesis of Abdominal Aortic Aneurysms (AAA). Available literature of genetic studies has previously suggested the possible roles of autoimmunity, genetic predisposition and ethnic susceptibility. Due to the association with autoimmune diseases and proven application in population genetics, we aimed to investigate alleles of the Class II Human Leukocyte Antigens (HLA-DRB1) in the Mexican Mestizo population with aortic aneurysms and determine possible associations with susceptibility. Methods We performed a case Control Study; the HLA molecular typing was completed for DRB1 loci by LabType Sequence-Specific Oligonucleotide (SSO) SSO-OneLambda kit (Applied Biosystems; Thermo Fisher Scientific. Inc.) in the studied individuals. Allele frequencies (af) were determined, associations were assessed by chi square or fisher exact tests at significance level (< 0.05), and Odds Ratios (OR) were calculated using the STATA software version 14. Results The genetic polymorphism of HLA-DRB1 of fifty one patients (70% males with a mean age of 71 years) with atherosclerotic or also known as degenerative AAA were compared with 99 unrelated patients (60% males, mean age 65 years) without the disease [Control group (CG)] from the same ethnic group. We examined a total of 102 Class II HLA-DRB1 alleles of AAA patients and 198 from CG. When comparing af, we observed the HLA-DRB1*01 af of 0.139 in the AAA compared to 0.05 in the CG [ p = 0.015, OR 3, 95% confidence interval (CI) 1.29–7.08], the HLA-DRB1*16 af were 0.109 in the AAA and 0.025 in CG ( p = 0.006, OR 4.7, 95% CI 1.59–13.98). Conclusions Our study confirmed increased frequencies of the alleles HLA-DRB1*01 and HLA-DRB1*16 and their association to the development of AAA in Mexican Mestizo patients. The utility of genetic testing may assist in identifying individuals at genetic risk for the development of this disease in different ethnic groups, who might benefit from earlier ultrasound screening and closer imaging surveillance.
Abstract. Despite the introduction of multidrug therapy and the overall reduction of leprosy prevalence in Mexico, the disease remains endemic in certain regions of the country. A genetic basis for the immune susceptibility to Mycobacterium leprae has already been established in different populations worldwide. In this study, we investigated the possible association of the HLA-DRB1 alleles with leprosy in a Mexican Mestizo population. The results demonstrated that the HLA-DRB1*01 allele is associated with lepromatous and dimorphic leprosy [P<0.001, odds ratio (OR)= 4.6, 95% confidence interval (95% CI): 1.8-11.4; and P=0.03, OR=6.2, 95% CI: 1.1-31.6, respectively] and the frequency of the HLA-DRB1*08 allele was found to be significantly lower among leprosy patients compared to controls (P=0.046, OR=2.4, 95% CI: 1-5.8). In conclusion, although the association of the HLA-DR locus with leprosy has been established in different populations and several studies have demonstrated significant differences in the DR alleles, this study demonstrated an association of the HLA-DRB1*01 allele with susceptibility to lepromatous and dimorphic leprosy, as well as an association of the HLA-DRB1*08 allele with protection against leprosy in a Mexican Mestizo population.
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