RESUMO
The purpose of this review is to present the main aspects of the genetic component of autoimmune rheumatic diseases, including the characteristics of the multifactorial or polygenic inheritance model, and its monogenic forms, as well as the main associated genes in both cases. The epigenetic changes involved, and the influence of the environment and sex that confer greater risk to women suffering from any of these diseases. Finally, to make known the advances that the study of omic sciences has allowed, opening the way to a new molecular classification of these diseases, aimed at personalized medicine. A review of the literature of the last 5 years, of English-language publications, in the PubMed database was performed and 28 review articles, and 19 original articles were included. Knowledge of the genetic factors involved in the aetiology of autoimmune rheumatic diseases, thanks to the availability of molecular studies, allows a better understanding of their pathophysiology and the possibility of diagnosis and treatment based on molecular markers in the future.
Assuntos
Doenças Autoimunes , Doenças Reumáticas , Humanos , Feminino , Doenças Reumáticas/genética , Doenças Autoimunes/diagnóstico , BiomarcadoresRESUMO
INTRODUCTION: Pemphigus is an autoimmune blistering disease of skin and mucous membranes characterized by presence of IgG antibodies against desmoglein 3, and 1. Desmoglein 3 and 1 are presented in pemphigus vulgaris and pemphigus foliaceous, respectively. Desmoglein are transmembrane proteins that form part of cellular junctions called desmosomes. Major histocompatibility complex class II molecules have been related to autoimmune disease; in pemphigus vulgaris, different human lymphocyte antigens (HLA) were associated among different ethnic groups, such as HLA-DR4, HLA-DR14, and HLA-DR1. OBJECTIVE: to determine the allele HLA-DR genetic frequencies in Mexican patients with pemphigus. METHOD: Patients with clinical, histological, and immunofluorescence diagnosis monitored at the Dermatology Department of the Mexican General Hospital were included. DNA was extracted from blood samples and genetic recognition of HLA-DRß1 was performed by polymerase chain reaction and hybridization. Forty-three patients with pemphigus were included: 35 (81.4%) women and eight men (18.6%) between 16 and 85 years old. RESULTS: The HLA-DR14 and HLA-DR1 genetic frequencies were elevated among pemphigus patients and these alleles confer risk to pemphigus 2.2 and 3.3, respectively. CONCLUSION: These findings suggest that pemphigus vulgaris susceptibility is part of a general predisposition to present autoimmune diseases.
Assuntos
Autoimunidade/imunologia , Suscetibilidade a Doenças/imunologia , Epitopos/imunologia , Antígenos HLA-D/imunologia , Pênfigo/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos HLA/imunologia , Antígenos HLA-D/genética , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.
Assuntos
Variação Genética , Indígenas Norte-Americanos/genética , Americanos Mexicanos/genética , População/genética , População Negra/genética , Genoma Humano , Humanos , México , População Branca/genéticaRESUMO
A 65-year-old unemployed man, originally from Michoacán and currently living in Toluca, state of Mexico, presented for medical consultation for disseminated dermatosis in all body segments. The condition was limited to the head and neck, was bilateral and symmetrical, and was characterized by infiltrated and confluent erythematous-edematous plates of diverse diameter covering 90% of the upper and lower extremities (Figure 1). The ailment had 2 years' evolution and a progressive course. The patient was diagnosed in private practice as having atopic dermatitis. After exacerbation of symptoms, he was treated with deflazacort and hydroxychloroquine with no improvement. Results from lesion biopsies revealed sarcoidal granulomas and the patient was therefore referred to the dermatology department at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán for further study and treatment with the presumptive diagnosis of mycosis fungoides vs sarcoidosis.
Assuntos
Hanseníase Dimorfa/diagnóstico , Hanseníase Tuberculoide/diagnóstico , Micose Fungoide/diagnóstico , Idoso , Progressão da Doença , Humanos , Hanseníase Dimorfa/patologia , Hanseníase Tuberculoide/patologia , Masculino , México , Micose Fungoide/patologiaRESUMO
Infection with human papillomavirus (HPV), mainly HPV type 16, is the major etiologic factor associated with cervical cancer (CC), but HPV infection alone is not sufficient for progression of precursor lesions. Host genetic susceptibility may lead to abnormal immune response resulting from virus persistence. Several studies have suggested a possible association with specific human leukocyte antigen (HLA) class I and II alleles and CC, but results are not consistent. The association of genetic HLA class I (A and B) and HLA class II (DR*B1 and DQ*B1) haplotypes with HPV16-positive CC (n = 104) and base population controls (n = 104) was evaluated in this Mexican population study. Sequence-specific primer HLA genes were determined by polymerase chain reaction (PCR)-based methods in peripheral blood cell counts (PCR sequence-specific oligonucleotides). The cervical swabs of 208 women were tested for HPV16 by Hybrid Capture II. Allele and haplotype HLA frequencies, Hardy-Weinberg tests, and a haplotype homogeneity test were estimated using the Arlequin software v. 3.01. Odds ratio (OR) was calculated to compare cases and control women. Consistent associations across other studies in women with CC and infected by HPV16 were observed for HLA-DRB1*15 (OR, 3.9; 95% CI, 1.6-10.2) and the haplotype DRB1*15 DQB1*0602 (OR, 4.1; 95% CI, 1.4-12.7) compared with control women. The HLA-A2-B44-DR4-DQ*0302, HLA-A24-B35-DR16-DQ*0301, and HLA-A2-B40-DR4-DQ*0302 haplotypes showed a positive association with CC (OR, >1), whereas HLA-A2-B39-DR4-DQ*0302, HLA-A24-B35-DR4-DQ*0302, and HLA-A68-B40-DR4-DQ*0302 showed a negative association (OR, <1). These results support the hypothesis that some HLA class I and II haplotypes could be involved with susceptibility for developing CC.
Assuntos
Carcinoma/genética , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Papillomavirus Humano 16 , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Carcinoma/patologia , Carcinoma/virologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Haplótipos , Papillomavirus Humano 16/genética , Humanos , México , Pessoa de Meia-Idade , Invasividade Neoplásica , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Polimorfismo Genético , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
BACKGROUND: Several studies have reported a direct association between elevated plasma levels of inflammatory cytokines and worse functional class (New York Heart Association [NYHA]) and cardiac function, measured as left ventricular ejection fraction (LVEF). Thalidomide has recently shown to improve LVEF in chronic heart failure patients, accompanied by a marked decrease in plasma levels of tumor necrosis factor alpha (TNF-alpha). METHODS: In a randomized prospective open label study of men and women with heart failure (HF) due to ischemic and non-ischemic cardiomyopathy who had systolic dysfunction (LVEF <40%) and NHYA classification, functional classes II and III were assigned to control (without thalidomide, 60 patients) or thalidomide group (20 patients). The initial dose of thalidomide was 100 mg once a day, and it was increased to 100 mg twice a day after a period of 10 days, if the prior dosage was well-tolerated. Demographic characteristics, etiology of HF, prior myocardial infarction, co-morbidities associated were registered and laboratory routine test, TNF-alpha serum levels, and echocardiogram were obtained at the beginning and after 6 months of follow-up. RESULTS: Clinical status (NYHA) at the end of the follow-up period, improved moderately in both groups. TNF-alpha levels were initially of 5.88 +/- 0.9 and 6.49 +/- 1.82 vs. 6.32 +/- 1.6 and 7.94 +/- 3.8 pg/ml during follow-up, for thalidomide and control groups, respectively. There were non-significant differences in echocardiography variables. CONCLUSION: In conclusion, although there is a large amount of information supporting a direct relationship between TNF-alpha and worsening of symptoms and prognosis in patients with HF and recently, the beneficial effect on thalidomide treatment has been suggested, these preliminary observations should be confirmed in a larger prospective study, specially trying to clarify the action mechanisms.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangueRESUMO
Los pénfigos son un grupo de enfermedades ampollosas de piel y mucosas que histológicamente presentan ampollas intraepidérmicas por acantólisis y anticuerpos fijos y circulantes dirigidos contra la superficie celular de los queratinocitos. En pacientes mexicanos que padecen pénfigo, no se han determinado desequilibrios de presentación de antígenos del HLA, como se ha estudiado en otras poblaciones, por lo que se efectuó un estudio comparativo, prospectivo, transversal y observacional en 25 pacientes; 18 de ellos con pénfigo vulgar y 7 con pénfigo foliáceo a quienes se les tomó muestra de sangre periférica para la extracción de DNA, con el método de expulsión salina ("salting out"). Se realizó determinación de HLA-DR, amplificando la región HLA-DRB1, mediante la técnica de reacción de polimerasa en cadena (PCR) y se determi-naron cada uno de los alelos con oligonucleótidos específicos de alelos (ASO), utilizando el kit Amplicor Hoffman La Roche Basilea, Suiza.Los resultados mostraron que el HLA-DR14 (DR6) es más común en los pacientes con pénfigo, sobre todo pénfigo vulgar, que en la población sana control, esto concuerda con lo descrito en la literatura universal. Por otra parte, el HLA-DR1 representa un riesgo relativo mayor para el desarrollo de pénfigo foliáceo en nuestra población.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Antígenos HLA-DR/análise , México , Pênfigo/imunologia , Doenças Autoimunes , Antígenos de HistocompatibilidadeRESUMO
Existe predisposición genética para el desarrollo de diabetes mellitus. La retinopatía diabética es una de sus complicaciones. Los mestizos mexicanos tienen una prevalencia alta para el desarrollo de diabetes mellitus; por ello resulta importante su estudio en cuanto a la susceptibilidad o resistencia para el desarrollo de retinopatía diabética proliferativa en diabetes mellitus no insulinodependiente. Objetivos: Identificar los alelos del complejo mayor de histocompatibilidad como marcadores de susceptibilidad o resistencia al desarrollo de retinopatía diabética proliferativa en pacientes mexicanos con diabetes mellitus no insulinodependiente. Material y métodos: Fueron incluidos 50 pacientes que fueron clasificados de acuerdo a sus antígenos clase I y clase II del complejo mayor de histocompatibilidad. Los antígenos clase II fueron sometidos al análisis del DNA después de la amplificación de sus genes. Las diferencias significativas entre los dos grupos fueron analizadas por medio de la prueba de c2 y la prueba exacta de Fisher. Resultados: Se encontraron incrementos significativos del HLA-B35 y HLA-B40 en todos los pacientes estudiados. Conclusiones: Se observó un aumento significativo en la incidencia de DR6 como marcador de susceptibilidad al desarrollo de retinopatía diabética, así como el efecto protector de los antígenos DR9, DR10 y DR5. Aunque nuestro grupo es pequeño, encontramos resultados estadísticamente significativos que consideramos importantes.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade/análise , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Retinopatia Diabética/patologia , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
Antecedentes. La uveítis anterior aguda asociada al HLA-B27 es una enfermedad inflamatoria del ojo ampliamente conocida; la espondilitis anquilosante y la uveítis anterior aguda, bilateral alterna, no granulomatosa se asocia al HLA-B27 en un 30 por ciento de la población mexicana afectada con esta espondiloartropatía. Se han observado diferencias entre la uveítis anteriores agudas asociadas al HLA-B27 y aquellas que no lo presentan, considerándose como un factor pronóstico al antígeno B27. Objetivo. Determinar la prevalencia del antígeno HLA-B27 en la uveítis anteriores agudas idiopáticas y sus características clínicas, a fin de establecer la importancia del HLA-B27 en pacientes con uveítis en la población mexicana. Material y métodos. Se practicó examen oftalmológico completo y estudios de laboratorio a 30 pacientes que, de acuerdo a criterios de inclusión y exclusión, tuvieron el diagnóstico de uveítis anterior aguda no granulomatosa en la que no se demostró enfermedad sistémica asociadas a la uveítis. En caso necesario, se indicó tratamiento local con corticoesteroides y ciclopléjicos. La muestra de sangre para determinar HLA-B27 se envió al Servicio de Inmunología del Instituto Nacional de Nutrición Salvador Zubirán. Resultados. Se incluyeron 30 pacientes, 16 del sexo femenino y 14 del masculino, todos mestizos, edad entre 15 a 65 años con una media de 33.6 años. Ocho de los 30 pacientes tuvieron HLA-B27 positivo (26.7 por ciento). Los 22 restantes fueron HLA-B27 negativos; de éstos, 17 (72 por ciento) presentaron uveítis unilateral, once (50 por ciento) tuvieron recurrencias, 18 (81.8 por ciento) respondieron favorablemente al tratamiento tópico; la duración promedio del cuadro agudo fue de 24 días, la agudeza visual promedio fue 20/25. En los ocho pacientes con B27 positivo, los resultados porcentualmente fueron semejantes. La uveítis en los casos B-27 negativos presentaron: congestión ciliar en el 82 por ciento, depósitos retroqueráticos moderados en el 59 por ciento, celularidad leve en cámara anterior en el 72 porciento, sinequias en el 63 por ciento y la uveítis se consideró leve en el 72 por ciento...