Mestizo Patients Research Articles

Trisomy 1q41-qter and monosomy 3p26.3-pter in a family with a translocation (1;3): further delineation of the syndromes.

BackgroundTrisomy 1q and monosomy 3p deriving from a t(1;3) is an infrequent event. The clinical characteristics of trisomy 1q41-qter have been described but there is not a delineation of the syndrome. The 3p25.3-pter monosomy syndrome (MIM 613792) characteristics include low birth weight, microcephaly, psychomotor and growth retardation and abnormal facies.Case presentationA 2 years 8 months Mexican mestizo male patient was evaluated due to a trisomy 1q and monosomy 3p derived from a familial t(1;3)(q41;q26.3). Four female carriers of the balanced translocation and one relative that may have been similarly affected as the proband were identified. The implicated chromosomal regions were defined by microarray analysis, the patient had a trisomy 1q41-qter of 30.3 Mb in extension comprising about 240 protein coding genes and a monosomy 3p26.3-pter of 1.7 Mb including only the genes CNTN6 (MIM 607220) and CHL1 (MIM 607416), which have been implicated in dendrite development. Their contribution to the phenotype, regarding the definition of trisomy 1q41-qter and monosomy 3p26.3-pter syndromes are discussed.ConclusionWe propose that a trisomy 1q41-qter syndrome should be considered in particular when the following characteristics are present: postnatal growth delay, macrocephaly, wide fontanelle, triangular facies, frontal bossing, thick eye brows, down slanting palpebral fissures, hypertelorism, flat nasal bridge, hypoplasic nostrils, long filtrum, high palate, microretrognathia, ear abnormalities, neural abnormalities (in particular ventricular dilatation), psychomotor developmental delay and mental retardation. Our patient showed most of these clinical characteristics with exception of macrocephaly, possibly due to a compensatory effect by haploinsufficiency of the two genes lost from 3p. The identification of carriers has important implications for genetic counseling as the risk of a new born with either a der(3) or der(1) resulting from an adjacent-1 segregation is of 25% for each of them, as the products of adjacent-2 or 3:1 segregations are not expected to be viable.

Diagnóstico genotípico y fenotípico de tuberculosis ósea y miliar en un paciente VIH positivo en Bogotá, Colombia

Tuberculosis is the single most frequent cause of death by an infectious agent worldwide. Diagnosis of extra-pulmonary tuberculosis is not always possible through conventional methods, due to the long time required for cultures and the paucibacillary nature of samples; hence the need of rapid molecular methods. HIV infection increases the risk of tuberculosis, and HIV/tuberculosis coinfection is associated with higher mortality.We describe the case of a 56-year old mestizo male patient suspected of having tuberculosis who consulted the San Ignacio Hospital in Bogotá with a two-month history of a painful ulcerated lesion over the distal third area of the right forearm and in whom HIV coinfection was confirmed.Bone and pulmonary histological examination evidenced multiple granulomas, giant cells and fibrosis. Cultures and IS6110-PCR from lung and bone tissues were positive for Mycobacterium tuberculosis complex. Mycobacterium tuberculosis isolates were sensitive to first line drugs.

Expression of interleukin (IL)-19 and IL-24 in inflammatory bowel disease patients: a cross-sectional study

Interleukin (IL)-19 and IL-24 belong to the IL-20 subfamily, and are involved in host defence against bacteria and fungi, tissue remodelling and wound healing. Nevertheless, no previous studies have explored their expression in Mexican mestizo patients with inflammatory bowel disease (IBD). The aim of the study was to characterize and to enumerate peripheral and tissue IL-19- and IL-24-producing cells, as well as gene expression in patients with IBD with regard to its clinical activity. We studied a total of 77 patients with ulcerative colitis (UC), 36 Crohn's disease (CD) and 33 patients as control group (without endoscopic evidence of intestinal inflammation). Gene expression was measured by real-time-polymerase chain reaction (RT-PCR). Protein expression was detected in biopsies by immunohistochemistry and in freshly isolated peripheral blood mononuclear cells by flow cytometry. IL-19 and IL-24 gene expression was elevated significantly in patients with active IBD versus the inactive disease and non-inflammatory control groups (P < 0·05). However, IL-19- and IL-24-producing cells were only increased in active CD versus active UC and non-inflammatory tissues (P < 0·05). IL-19 was produced conspicuously by circulating B cells and monocytes in patients with inactive disease (P < 0·05). Conversely, IL-24 was noticeably synthesized by peripheral B cells, CD4(+) T cells, CD8(+) T cells and monocytes in patients with active disease. In conclusion, IL-19- and IL-24-producing cells in active CD patients were increased compared with active UC and non-inflammatory tissues. These cytokines could significantly shape and differentiate inflammatory process, severity and tolerance loss between UC and CD pathophysiology.

Genetic mutations in early‐onset Parkinson's disease Mexican patients: Molecular testing implications

Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.

Abstract T P168: Headache and Cerebral Venous Thrombosis

Background and purpose: Headache is the most frequent presenting symptom of cerebral venous thrombosis (CVT), but many aspects of its profile are unknown because large scale studies are scarce. We aimed to analyze the headache characteristics in the largest cohort of Hispanic Mestizo patients with CVT. Methods: Since 1986 a systematic CVT registry has been carried out in 2 tertiary referral Neurological centers in Mexico City. Herein we examine the headache profile and the association of demographic, clinical and neuroimaging factors with the occurrence of headache in 408 consecutive patients. Results: Among 408 patients (82% women) included in this registry, headache occurred in 346 (85%; 86% in women, 79% in men, p NS), being the first neurological manifestation in 309 (76%). Headache onset was acute in 46%, of gradual onset in 51%, and a sudden explosive onset like thunderclap occurred in 3%. A diffuse headache pattern occurred in 56%, bifrontal in 22%, unilateral in 15%, and suboccipital in 8%. It was of pulsatile quality in 73%, and oppressive in 24.3%, and it was mostly deemed as severe (49%) or moderate (47%) in intensity, described as progressive in 19%, and with nausea or vomiting in 52% patients. Headache was the only neurological symptom in 58 patients (14%): as part of an isolated intracranial syndrome in 52 (13%) and as the sole manifestation of CVT in 6 (1.5%). Headache was followed by other neurological symptoms in 70%, appearing within 48 hours of headache onset in 33%, within 3-6 days in 34%, within 7-10 days in 16%, and after 10 days in 18%. CVT diagnosis was significantly delayed in patients with headache, as compared with other neurological presentations (delay &gt;15 days: 30% vs. 8%, respectively; p&lt;0.05). There were not differences in anatomical topography of CVT in patients presenting with headache, as compared with other neurological features. Conclusions: There is no identifiable, uniform, recognizable pattern of headache in CVT and often precedes the development of other neurological deficits for days or even weeks delaying the diagnosis of CVT. Interestingly, neither the presence nor the quality of headache is associated with the topography or extension of CTV.

Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.

150-P: POLYMORPHISM OF MICA IN HELICOBACTER PYLORI-POSITIVE MEXICAN PATIENTS WITH GASTRODUODENAL LESIONS

MHC class I chain related gene A (MICA) is a highly polymorphic gene expressed in gastrointestinal epithelial cells. MICA activates NK and gamma delta T cells trough the binding of NKG2D receptor under cellular stress situations (infection or transformation). Helicobacter pylori (H. pylori) colonization of the gastric mucosa is a major cause for chronic gastritis and predisposition for peptic ulcer and gastric cancer. We analyze the associations between allelic and microsatellite polymorphism of MICA, and gastroduodenal lesions related to H. pylori infection in Mexican Mestizo patients. We genotyped by RSCA technique 282 H. pylori-positive patient samples diagnosed by endoscopy and histology (non-atrophic gastritis=139, intestinal metaplasia=67, gastric cancer=34 and duodenal ulcer=42), and 96 H. pylori seropositive asymptomatic persons without gastric lesions. The allelic and microsatellital frequencies in the different groups of patients were statistically compared by chi-square and Fisher test (pc < 0.05). We found in the asymptomatic group five microsatellites: A4 (5.8%), A5 (25.2%), A5.1 (10.7%), A6 (18.0%) and A9 (40.3%) and six MICA alleles: ∗001 (5.2%), ∗00201 (40.6%), ∗004 (17.2%), ∗00801 (10.9%), ∗010 (25.0%) and ∗011 (1.1%). In patients we observed a decrease of the 00201/00201 genotype frequency in duodenal ulcer (9.5%) when compared with non-atrophic gastritis (20.0%) and asymptomatics (23.0%), but it was not statistically significant. We did not find any association with gastric cancer. These results strongly suggest that the MICA polymorphism may not be associated with the gastroduodenal diseases provoked by H. pylori infection in Mexican population. (CONACyT 6957, FOFOI 2001/007 and 2002/110).

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: Data from a Latin American cohort

The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. Systemic lupus erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR 3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50-0.99). Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

Central Adiposity and Mortality after First-Ever Acute Ischemic Stroke

Background: The waist-to-height ratio (WHtR) may be a better adiposity measure than the body mass index (BMI). We evaluated the prognostic performance of WHtR in patients with acute ischemic stroke (AIS). Methods: First, we compared WHtR and BMI as adiposity measures in 712 healthy adults by tetrapolar bioimpedance analysis. Thereafter, baseline WHtR was analyzed as predictor of 12-month all-cause mortality in 821 Mexican mestizo adults with first-ever AIS by a Cox proportional hazards model adjusted for baseline predictors. Results: In healthy individuals, WHtR correlated higher than BMI with total fat mass and showed a higher accuracy in identifying a high percentage of body fat (p < 0.01). In AIS patients a U-shaped relationship was observed between baseline WHtR and mortality (fatality rate 29.1%). On multivariate analysis, baseline WHtR ≤0.300 or >0.800 independently predicted 12-month all-cause mortality (hazard ratio 1.91, 95% confidence interval 1.04-3.51). BMI was not associated with mortality, tested either as continuous, binomial or stratified variable. Conclusion: WHtR is a modifiable risk factor that accurately demonstrates body fat excess. Extreme WHtR values were associated with increased 12-month all-cause mortality in Mexican mestizo patients with AIS. No survival advantage was found with high WHtR as the pragmatic indicator of obesity in this population.

Association of HLA-DRB1*15 and HLA-DQB1* 06 with SLE in Saudis

BACKGROUND AND OBJECTIVESSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by humoral autoimmunity. The etiology of SLE is thought to be multifactorial including environmental, hormonal, and genetic factors. The human leukocyte antigen (HLA) has extensively been associated with the susceptibility to SLE; however, the association is heterogeneous among different ethnic groups. The aim of this study was to determine the association of HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1 with SLE susceptibility in the Saudi population.DESIGN AND SETTINGSA total of 86 consecutive SLE patients attending the rheumatology clinic at King Abdulaziz Medical City, Riyadh, were recruited for this study.METHODSHLA types were determined by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSP) method in 86 patients and 356 control subjects.RESULTSThe following HLA alleles were found to be positively associated with SLE: HLA-A*29 (OR=2.70; 95% CI=1.03–7.08; P=.0035), HLA-B*51 (OR=1.81; 95% CI=1.17–2.79; P=.0066), HLA-DRB1*15 (OR=1.45; 95% CI=0.98–2.29; P=.063), and HLA-DQB1*06 (OR=1.67; 95% CI=1.19–2.36; P=.0032), whereas HLA-DRB1*16 was negatively associated with the disease (OR=0.18; 95% CI=0.02–1.3; P=.055). HLA-DRB1*15 haplotypes were significantly associated with SLE (OR=2.01, 95% CI=1.20–3.68, P=.008); this was mainly due to the HLA-DRB1* 15-DQB1*06 association.CONCLUSIONSOur data suggest an association between MHC class I and class II (HLA-A*29, HLA-B*51, HLA-DRB1*15, and HLA-DQB1*06) and susceptibility to SLE in the Saudi population. HLA-DRB1*15-DQB1*06 haplotype showed the highest risk factor for the disease that is similar to what was seen in the African American patients, suggesting shared susceptibility genetic factors among these ethnic groups.

Interleukin-10 gene polymorphisms (-1082 A/G, -819 C/T, -592 C/A) in primary Sj�gren's syndrome

Event Abstract Back to Event Interleukin-10 gene polymorphisms (-1082 A/G, -819 C/T, -592 C/A) in primary Sjögren's syndrome Edith Oregon-Romero1*, Mirna Vázquez-Villamar1, Diana C. Salazar-Camarena1, Beatriz A. Treviño-Talavera1, Gerardo Orozco-Barocio2, José F. Muñoz-Valle1, Yeminia M. Valle-Delgadillo1 and Claudia A. Palafox-Sánchez1, 2 1 Universidad de Guadalajara, Mexico 2 Hospital General de Occidente, Servicio de Reumatología, Mexico Introduction: Primary Sjögren´s syndrome (pSS) is an autoimmune disease of unknown etiology affecting primarily salivary and lacrimal exocrine glands. It is characterized by a progressive lymphocytic infiltration where B cells produce a great variety of antibodies, including those against ribonucleoproteins Ro and La. IL-10 plays an important role in pSS by promoting the differentiation of B cells inducing antibody production. Three polymorphic sites located at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the IL-10 promoter show a linkage disequilibrium and form haplotypes that may influence the IL-10 production and consequently an increased activity of the disease. Objective: To determine the frequency of haplotypes in the IL-10 promoter gene in patients with pSS. Methodology: The study included 113 Mexican mestizo patients with pSS, classified according to the American-European Consensus criteria, from the Department of Rheumatology (Hospital General de Occidente, SSJ). As control group, 154 clinically healthy subjects were included. The polymorphisms were genotyped by PCR/RFLP technique. Statistical analysis was carried out with the Stata 9.0 and EmHapFre software. Results: Polymorphisms were in Hardy–Weinberg equilibrium (-1082 A/G p=0.8377, -819C/T p= 0.1174, -592 C/A p=0.7953) and showed high linkage disequilibrium (100%, pc=1.42 x 10-34).The most frequent haplotypes were: ACC (41-61%), ATT (21.38%), GTA (14.86%), and GCC (11.18%). GTC haplotype was associated with a 4.35-fold less probability to develop pSS [OR; 95%CI: 0.23 (0.064-0.792) p= 0.01]. Conclusion: Our results suggest that carriers of the GTC haplotype have a protective status for the development of pSS. Keywords: primary Sjögren´s syndrome, Antibodies, IL-10 promoter, Linkage Disequilibrium, Haplotypes Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Oregon-Romero E, Vázquez-Villamar M, Salazar-Camarena DC, Treviño-Talavera BA, Orozco-Barocio G, Muñoz-Valle JF, Valle-Delgadillo YM and Palafox-Sánchez CA (2013). Interleukin-10 gene polymorphisms (-1082 A/G, -819 C/T, -592 C/A) in primary Sjögren's syndrome. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00346 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Edith Oregon-Romero, Universidad de Guadalajara, Guadalajara, Mexico, oregon_edith@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez Google Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez Google Scholar Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez PubMed Edith Oregon-Romero Mirna Vázquez-Villamar Diana C Salazar-Camarena Beatriz A Treviño-Talavera Gerardo Orozco-Barocio José F Muñoz-Valle Yeminia M Valle-Delgadillo Claudia A Palafox-Sánchez Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The −174G/C and −572G/C Interleukin 6 Promoter Gene Polymorphisms in Mexican Patients with Rheumatoid Arthritis: A Case-Control Study

Objective. There is a lack of information about the genotype frequencies of IL-6 −174G/C and −572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 −174G/C and −572G/C polymorphisms in Mexican mestizo with RA. Methods. We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 −174G/C and −572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. Results. The genotype −174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype −572GG (54% in patients versus 60.8% in controls, P = 0.295). Conclusions. This is the first study to evaluate the association of −174G/C and −572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.

Indoleamine 2,3-Dioxygenase: Expressing Cells in Inflammatory Bowel Disease—A Cross-Sectional Study

Aim. To characterise and enumerate IDO+ cells, Tregs, and T cell subsets in patients with ulcerative colitis (UC) and Crohn's disease (CD) with regard to their clinical activity. Methods. Ten active UC (aUC), 10 inactive UC (iUC), 6 aCD, and 8 iCD patients and 10 healthy individuals were included in the study. Circulating Foxp3-, IDO-, IL-17A-, IL-4-, IFN-γ-, and IL-10-expressing CD4+ T cells were quantitated by flow cytometry. Interleukin-17-expressing cells, CD25+/Foxp3+ Tregs, and CD123+/IDO+ plasmacytoid dendritic cells were evaluated in intestinal biopsies from 10 aUC, 6 aCD, and 10 noninflamed tissues. Results. All CD4+ T subsets were increased in aIBD patients compared with healthy donors. Meanwhile, frequency of CD8α +/CD16+/IDO+, CD8α +/CD56+/IDO+, CD8α +/CD80+/IDO+, CD8α +/CD123+/IDO+ large granular nonlymphoid cells, and CCR6+/CD123+/IDO+ plasmacytoid dendritic cells was higher in aIBD patients versus healthy donors or iIBD patients. Tissue IL-17A+ cells were present in higher amounts in aIBD versus noninflamed controls. IDO- and Foxp3-expressing cells were increased in aUC versus aCD patients and noninflamed tissues. Conclusions. The findings represent an original work in Mexican Mestizo patients with IBD. It shows that Tregs and IDO-expressing cells are increased with regard to disease activity. These cells could significantly shape inflammatory bowel disease pathophysiology, severity, and tolerance loss.

Antiphospholipid antibodies in Mexican HIV-positive patients

Several studies have shown that HIV patients tend to develop autoimmune diseases, and have numerous antibodies, such as antiphospholipid antibodies. Antiphospholipid antibodies are the serological markers used in the diagnosis of the antiphospholipid syndrome. However, antiphospholipid antibodies also appear to exist in infectious diseases. ObjectiveTo measure the titers of antiphospholipid antibodies in healthy and in HIV positive Mexican mestizo patients, and correlate them with the patient clinical manifestations to identify possible findings compatible with an autoimmune disease. Material and methodsA case control study was conducted on 50 healthy mixed race Mexican subjects and in 50 randomly selected HIV-positive patients from the Infectious Diseases Department of a Regional Hospital in Puebla, México. Antiphospholipid titers were performed on the patients and controls and analyzed to see if there was any correlation between clinical signs. ResultsThere was a statistical difference in the titers of anticardiolipin antibodies isotype IgG between the control group and the HIV group. When sexual preference was evaluated in the HIV group a statistical difference in the antibody titers was observed between homosexual and heterosexual HIV patients. ConclusionThere were no correlations found between the antibody titers and specific clinical manifestations in HIV positive patients. The exact clinical meaning of the presence of these antibodies in HIV positive patients is still unknown, so further studies are needed.

Genetic association of IFN-γ +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, but potentially life-threatening diseases, characterized by widespread epidermal necrosis and are predominantly drug induced. There is a paucity of data regarding the role of cytokine and cytokine receptors polymorphisms in the pathoimmunology of SJS/TEN. The aim of this study was to investigate the role of TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg gene polymorphisms in SJS/TEN in Mexican Mestizo patients. Twenty-nine unrelated SJS/TEN patients and 128 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR-RFLP method was used to amplify the following polymorphisms: TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg. TNF-α-308, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg polymorphisms were not associated with the genetic susceptibility to SJS/TEN. The distribution of TT, TA, AA genotypes of IFN-γ +874 was significantly different in SJS/TEN patients compared with controls (pC = 0.012). TA and AA genotypes were grouped to highlight the differences between patients and controls given by the absence of the AA genotype in the group of patients (pC = 0.03, OR = 3.61 95 % CI 1.20-11.6). This preliminary study suggests that IFN-γ +874 T/A polymorphism is associated with SJS/TEN.

Hearing Impairment in a Tertiary-Care-Level Population of Mexican Rheumatoid Arthritis Patients

The objectives of this study were to assess characteristics of hearing impairment (HI) in Mexican Mestizo patients with rheumatoid arthritis. One hundred thirteen consecutive patients (101 women, aged 43.3 ± 13.1 years) without previously identified HI diagnosis had a structured interview and complete rheumatic and audiologic evaluations, which included at least a pure-tone audiometry and standard and high-frequency tympanometry. Hearing impairment was defined if the average thresholds for at least 1 of low-, mid-, or high-frequency ranges were 25-dB hearing level or greater in 1 ear (unilateral) or both ears (bilateral). Hearing impairment was classified as mild or moderate/severe. Appropriate statistics, multivariate analysis, and receiver operating characteristic curves were used. Hearing impairment was detected in 27 patients (24%), was sensorineural-type HI in 25 (93%), bilateral in 14 (52%), and mild in 20 of them (74%). Normal tympanograms (type A) were found in 93 patients (82%), although high-frequency tympanometry was abnormal in 80 patients (71.4%). Patients with HI were significantly older (51.8 ± 14.1 vs. 40.7 ± 11.7 years, P ≤ 0.001), had more frequent rheumatoid nodules (37% vs. 12.8%, P = 0.001), and had more (median [range]) comorbidities per patient (2 [1-2] vs. 1 [0-2], P = 0.03). Multivariate analysis showed that HI was significantly associated to age (odds ratio, 1.1; 95% confidence interval, 1.03-1.15; P ≤ 0.001). The best cutoff level for HI was 50 years of age and increased to 59 years for moderate/severe HI. A significant proportion of Mexican Mestizo outpatients with rheumatoid arthritis had previously undiagnosed HI, mainly of sensorineural type, of mild severity, and bilateral. Older age was the only prognosticator of HI.

Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus

BackgroundSystemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity and the production of pathogenic anti-nuclear-directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored.MethodsRelative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann–Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman’s ranking.ResultSLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells.ConclusionsOur data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.

Genetic polymorphisms of interleukin 20 (IL-20) in patients with ulcerative colitis

Interleukin (IL)-20 belongs to the IL-10 family and is a potent immunomodulatory cytokine with implications for pathogenesis in the inflammatory bowel disease (IBD). The interleukin 20 gene is located within a 200kb region of q31-32 locus of chromosome 1. No previous studies have reported this novel association between ulcerative colitis (UC) and IL-20 polymorphisms. In the present work, we evaluated the role of IL-20 gene polymorphisms as susceptibility markers for UC. Three polymorphisms of IL-20 gene (rs2981573, rs2232360, rs1518108) were genotyped by 5′ exonuclease TaqMan genotyping assays on an ABI Prism 7900 HT Fast Real-Time PCR system in a group of 198 Mexican Mestizo patients with UC and 698 ethnically matched healthy unrelated individuals with no family history of UC. We found significant decreased frequencies of two IL-20 genotypes: GG (rs2981573) [10.6% vs. 17.6%, p=0.017, OR=0.55, 95% CI: 0.33–0.93] and GG (rs2232360) [10.6% vs. 17.6%, p=0.017, OR=0.55, 95% CI: 0.33–0.93] in UC patients as compared to healthy controls. No significant differences of gene frequencies were found between UC patients and healthy controls in the rs1518108 polymorphism. In the subgroup analysis, no differences were found between the IL-20 genotypes and the clinical characteristics of UC. The results suggest that the GG genotypes of the IL-20 polymorphisms (rs2981573 and rs2232360) might have an important role in the development of UC in the Mexican population.

Primary thrombophilia in Mexico IX

The sticky platelet syndrome (SPS) seems to be a common cause of thrombosis, although no molecular substrate to explain platelet hyperaggregability has been found. To analyze an association between the SPS phenotype and the platelet glycoprotein (GP) IIIa PL(A1/A2) (human platelet antigen [HPA]-1a/b) gene polymorphism. Along an 18-month period, Mexican mestizo thrombophilic patients were prospectively accrued. The SPS phenotype was assessed by aggregometry, whereas a tetra-primer amplification refractory mutation system (ARMS) polymerase chain reaction analysis was used to detect the PLA1 and PLA2 alleles. A total of 95 individuals with SPS and 127 healthy donors were studied; in 11 of the donors and 16 of the patients with SPS the A2 allele of the GP IIb/IIIA was found, yielding a weak and nonsignificant association (odds ratio 2.14, 95% CI 0.94-4.85). In Mexican mestizo patients, the platelet GP IIIa PL(A1/A2) gene polymorphism does not lead to the SPS phenotype.

Disease Severity in Patients Infected with Leishmania mexicana Relates to IL-1β

Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, yet little is known about factors regulating disease severity in these patients. We analyzed if the disease was associated with single nucleotide polymorphisms (SNPs) in IL-1β (−511), CXCL8 (−251) and/or the inhibitor IL-1RA (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control cases. Additionally, we analyzed the in vitro production of IL-1β by monocytes, the expression of this cytokine in sera of these patients, as well as the tissue distribution of IL-1β and the number of parasites in lesions of LCL and DCL patients. Our results show a significant difference in the distribution of IL-1β (−511 C/T) genotypes between patients and controls (heterozygous OR), with respect to the reference group CC, which was estimated with a value of 3.23, 95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1β (−511 C/T) represents a variable influencing the risk to develop the disease in patients infected with Leishmania mexicana. Additionally, an increased in vitro production of IL-1β by monocytes and an increased serum expression of the cytokine correlated with the severity of the disease, since it was significantly higher in DCL patients heavily infected with Leishmania mexicana. The distribution of IL-1β in lesions also varied according to the number of parasites harbored in the tissues: in heavily infected LCL patients and in all DCL patients, the cytokine was scattered diffusely throughout the lesion. In contrast, in LCL patients with lower numbers of parasites in the lesions, IL-1β was confined to the cells. These data suggest that IL-1β possibly is a key player determining the severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8 and IL-1RA showed no differences between patients with different disease severities or between patients and controls.