Predictors of remission, erosive disease and radiographic progression in a Colombian cohort of early onset rheumatoid arthritis: a 3-year follow-up study.

The objective of the study is to find predictors of remission, radiographic progression (RP), and erosive disease in a cohort of patients with early onset rheumatoid arthritis (EORA) that followed a therapeutic protocol aiming at remission, in a real world tight-control setting. EORA patients were enrolled in a 3-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed. Radiographs were scored according to Sharp-van der Heijde (SvdH) method. RP was defined by an increase of 3 units in 36 months. Remission was defined as DAS28 <2.6. A stepwise multiple logistic regression model was used to identify independent predictors of the three target outcomes. One hundred twenty-nine patients were included. Baseline disease activity was high. Significant overall improvement was observed, but only 33.3 % achieved remission. At 36 month, 50.4 % (65) of patients showed erosions. RP was observed in 62.7 % (81) of cases. Statistical analysis showed that baseline SvdH score was the only predictive factor associated with the three outcomes evaluated. Lower HAQ-DI and absence of autoantibodies were predictive of remission. Higher levels of ESR and presence of erosions at entry were predictive of RP. Independent baseline predictors of incident erosive disease were anti-CCP and RF positivity, symptom duration at baseline >3 months, and presence of HLA-DRB1 shared epitope. Radiographic damage at baseline was the main predictor of outcomes. Autoantibodies, HAQ and ESR at baseline, symptom duration before diagnosis, and HLA-DRB1 status had influence on clinical course and development of structural joint damage in Colombian RA patients.

Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population.

INTRODUCTION: Late-onset systemic lupus erythematosus (SLE) represents a specific subgroup that is defined as onset after 50 years of age. Late-onset lupus may have a different clinical course and serological findings, which may delay diagnosis and timely treatment. OBJECTIVES: The objective of this paper is to determine the clinical, serologic, and immunogenetic differences among Colombian patients with late-onset SLE versus conventional SLE patients. METHODOLOGY: This was a cross-sectional study in a Colombian population. Patients and their medical records were analyzed from the services of Rheumatology in Bogotá and met the criteria for SLE, according to the American College of Rheumatology (ACR) revised criteria for the classification of SLE.In a reference group of late-onset SLE patients (98 participants, with an onset after 50 years of age) and a group of conventional SLE patients (72 participants, with an onset of age of 49 years or less), multiple clinical variables (age, clinical criteria for lupus, alopecia, weight loss, fever, Raynaud's phenomenon) and multiple serological variables (blood count, blood chemistry profile, autoantibodies) were analyzed. Additionally, the HLA class II (DRB1) of all the patients was genotyped, including an additional group of patients without the autoimmune disease. Statistical analysis was performed using the STATA 10.0 package. RESULTS: In the group of late-onset lupus, there was a higher frequency of pleurisy (p = 0.002), pericarditis (p = 0.026), dry symptoms (p = 0.029), lymphopenia (p = 0.007), and higher titers of rheumatoid factor (p = 0.001) compared with the group of conventional SLE. Late-onset SLE patients had a lower seizure frequency (p = 0.019), weight loss (p = 0.009), alopecia (p < 0.001), and Raynaud's phenomenon (p = 0.013) compared to the conventional SLE group. In late-onset SLE, HLA DR17 (DR3) was found more frequently compared with individuals without autoimmune disease (OR 3.81, 95% CI 1.47 to 10.59) (p = 0.0016). CONCLUSION: In the Colombian SLE population analyzed, there may be a probable association of several clinical and serologic variants, which would allow the differentiation of variables in the presentation of the disease among patients with late-onset SLE vs. conventional SLE.

Association study of polymorphisms in LRP1, tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients.

Analysis of genetic susceptibility factors for Alzheimer's disease (AD) in populations with different genetic and environmental background may be useful to understand AD etiology. There are few genetic association studies of AD in Latin America. In the present work, we analyzed polymorphisms in 3 candidate genes; the LDL receptor related protein-1, the microtubule-associated protein Tau and the serotonin transporter genes in a sample of 106 Colombian AD patients and 97 control subjects. We did not find a significant allelic or genotypic association with any of the three polymorphisms analyzed using different statistical analysis, including a neural network model or different sample stratifications. To date, APOE polymorphisms are the only genetic risk factors identified for AD in the Colombian population. It may be factible that future combination of high-throughput genotyping platforms and multivariate analysis models may lead to the identification of other genetic susceptibility factors for AD in the Colombian population.

Gastritis crónica en el Hospital San Juan de Dios y Clínica Carlos Lleras Restrepo de Bogotá, Universidad Nacional de Colombia / Chronic gastritis

La patología gástrica inflamatoria es una causa importante de morbilidad en nuestro medio. Condiciones específicas como la gastritis crónica atrófica multifocal, la metaplasia intestinal y la displasia gástrica se encuentran asociadas con el proceso de múltiples pasos en el desarrollo del adenocarcinoma gástrico de tipo intestinal. En este estudio, descriptivo retrospectivo, se revisó el archivo de quirúrgicos del Hospital San Juan de Dios y de la Clínica Carlos Lleras Restrepo de Bogotá, en el periodo comprendido entre el 1 de enero de 1.999 y el 31 de Mayo de 2.000, encontrando 9.349 casos. Dentro de éstos, la patología gástrica correspondió a 18,6 por ciento (1.742), de los cuales 1585 casos ( 90 por ciento) correspondieron a patología no tumoral Se seleccionaron 1.387 casos de los diferentes tipos de gastritis, los cuales fueron clasificados de acuerdo al sistema Sydney modificado del consenso internacional de Houston de 1994. Se encontró una asociación de gastritis crónica y H. pylori del 74,62 por ciento. La gastritis crónica no atrófica se presentó más frecuentemente (73,46 por ciento), afectando personas entre los 40 y 60 años y su asociación con H. pylori fue del 80 por ciento. La gastritis crónica atrófica ocupó el segundo lugar en frecuencia (26,46 por ciento), predominando en mujeres, y con una asociación significativa a infección por H. Pylori (63,31 por ciento).Todos los casos de displasia se presentaron asociados con gastritis crónica atrófica multifocal. Además, se encontró que la presencia de gastritis crónica atrófica multifocal y displasia representan un mayor riesgo relativo (2,2) de desarrollo de adenocarcinoma gástrico

Genetic relationship of the Guambino, Paez, and Ingano Amerindians of southwest Colombia using major histocompatibility complex class II haplotypes and blood groups.

We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively). The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia.

Apolipoprotein E genotyping in a sample of Colombian patients with Alzheimer's disease.

Apolipoprotein E e4 (APOEe4) allele has been associated with an increased risk for Alzheimer's disease (AD) in diverse populations. Few studies have been carried out in Hispano-Americans and results are inconclusive due to ethnic diversity. This study determined the frequency of APOE alleles in a group of 61 Caucasian-Mestizos patients with probable AD, and 61 age- and sex-matched controls. APOEe4 frequency was 36.8% for patients, and 8.2% for controls (P < 0.0001; OR 7.6). Genotype frequencies differ between the two groups (P < 0.0001). Genotype 3/3 was the most common. Frequency of genotypes 3/4, 4/4 and 2/4 were higher in patients than in the controls. Our results show a highly significant association of APOEe4 with AD, and implies the importance of APOEe4 as a risk factor in this population.

Population data on 6 short tandem repeat loci in a sample of Caucasian-Mestizos from Colombia.

Blood samples from 409-452 unrelated Colombian Caucasian-Mestizo individuals were amplified and typed for six short tandem repeat (STR) markers (HUMF13A01, HUMFES/FPS, HUMVWA, HUMCSF1PO, HUMTPOX, HUMTH01). The allele frequencies, genotype frequencies, heterozygosity, mean paternity exclusion chance, polymorphism information content, discrimination power, assumption of independence within and between loci and Hardy Weinberg equilibrium were determined. The results demonstrate that all markers conform to Hardy-Weinberg equilibrium expectations. In addition, the results demonstrate the assumption of independence within and between the loci analysed. The mean exclusion chance (MEC) was 0.9851 for all six STR loci analysed and the discrimination power (DP) was 0.9999973. Therefore, this Colombian population database can be used in identity testing to estimate the frequency of a multiple PCR-based locus DNA profile in forensic cases as well as in paternity testing.

Population frequency for the short tandem repeat loci D18S849, D3S1744, and D12S1090 in Caucasian-Mestizo and African descent populations of Colombia.

Blood samples from 489 unrelated Caucasian Mestizo and 252 individuals of African descent in Colombia were amplified and typed for three short tandem repeat (STR) markers (D12S1090, D3S1744, and D18S849). All markers conformed to Hardy-Weinberg equilibrium expectations in both populations studied. In addition, heterozygosity, mean exclusion chance, polymorphism information content, discrimination power, and the assumption of independence within and between loci were determined. The mean exclusion chance for all three STR markers is 0.9750 in the Caucasian Mestizo population and 0.9731 in the African Colombian Population. The discrimination power is 0.999925 and 0.999911 in the Caucasian Mestizo and African Colombian respectively.

Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.

BACKGROUND: Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. OBJECTIVE: To study the influence of the MHC class I and class II genes in the susceptibility to atopic asthma. METHODS: MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). RESULTS: MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.0 17, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC = 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC<0.05). The HLA-DRB1*1101, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC< 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P<0.001) and Der f (median, 46.9 vs 2.7 kU/L, P<0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. CONCLUSIONS: We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.

Major histocompatibility complex class II alleles and haplotypes and blood groups of four Amerindian tribes of northern Colombia.

MHC class II alleles and haplotypes were determined from unrelated individuals and families of the Arhuaco (n = 107), Kogi (n = 42), Arsario (n = 18), and Wayú (n = 88) tribes located in the northern part of Colombia. Class II DRB, DQA1, and DQB1 alleles were determined by PCR-SSO and PCR-RFLP based methods. Four haplotypes, [DRB1*0407, DRB4*0101, DQA1*03, DQB1*0302]; [DRB1*0403, DRB4*0101, DQA1*03, DQB1*0302]; [DRB1*1402/1406, DRB3*0101, DQA1*0501, DQB1*0301]; and [DRB1*0802, DQA1*0401, DQB1*0402], were observed among these four tribes. In addition to these haplotypes, the Wayú Indians showed a frequency of 21.3% for the [DRB1*1602, DRB5*02, DQA1*0501, DQB1*0301] haplotype, 13.1% for the [DRB1*0411, DRB4*0101, DQA1*03, DQB1*0302] haplotype, and 8.1% for the [DRB1*0411, DRB4*0101, DQA1*03, DQB1*0402] haplotype. Red cell antigen typing was used to calculate genetic admixture. The Kogi and Arsario showed no genetic admixture while the Arhuaco tribe showed admixture with genes of African origin and the Wayú showed admixture with Caucasians as well as genes of African origin. These findings were confirmed by the MHC class II allele and haplotype data obtained, as alleles and haplotypes of Caucasian and African origin were detected in the Wayú and Arhuaco and not in the Kogi or Arsario. These studies will be important in disease association and transplantation studies for Amerindian and colombian populations and for correlating genetic traits with the anthropologic and linguistic data available in order to better understand the Amerindian populations.

Molecular quantification of residual disease in chronic myelogenous leukemia after bone marrow transplantation.

Residual disease remains a major problem in the treatment of human neoplasia. To effectively monitor minimal leukemic activity after bone marrow transplantation (BMT), we used a competitive polymerase chain reaction (PCR) amplification technique to quantify expression of the characteristic bcr-abl fusion message in patients with chronic myelogenous leukemia (CML). Quantitative results were obtained between the 0.001% and 0.1% level in control experiments. This represents a significant advantage over cytogenetic and Southern blotting techniques routinely used to diagnose CML, which may not be sensitive below the 1% level. To illustrate the potential clinical usefulness of the quantitative PCR strategy, we compared results of bcr-abl messenger RNA expression with those obtained using cytogenetic and Southern blotting techniques, in a study of consecutive BM and peripheral blood (PB) samples from two CML patients at high risk for relapse after BMT. One patient received a syngeneic transplant during the chronic phase of the disease and relapse was apparent at the molecular level 4.5 months after BMT, while the patient was in complete clinical remission. The second patient was treated with an allogeneic BMT during the accelerated phase of the disease. A slow, but progressive decrease in bcr-abl expression was observed during the first 12 months after BMT, and expression was undetectable thereafter. Our results indicate that the competitive PCR technique can be used to monitor disease activity in patients at high risk of relapse, while the patients are in complete clinical remission, which should facilitate the early detection of relapse or the identification of progressive disappearance of leukemic activity. The approach used may serve as a model for the study of residual disease in an increasing number of other hematologic malignancies that express cancer-specific RNAs.

Familial occurrence of the aniridia-Wilms tumor syndrome with deletion 11p13-14.1.

A report of a family with two half-brothers and a maternal aunt affected with the aniridia-Wilms tumor syndrome is presented. The proband showed a deletion of most of band 11p13 and of subband 11p14.1 of one chromosome 11, and the proband's mother and an older brother, both phenotypically normal, showed a balanced chromosomal rearrangement. This family demonstrates that deletion of a small chromosome segment (11p13-14.1) is responsible for the aniridia-Wilms tumor syndrome and, that in some cases, the syndrome can be familial.