RESUMEN

Type 1 diabetes mellitus is a clinical condition characterized by insufficient insulin production due to progressive loss of pancreatic islet ß-cells mediated by an autoimmune response. This deregulation of the immune system is caused by the action of genetic, epigenetic, and environmental factors in varying combinations for each individual. Although the inflammation of the islets with immune cell infiltration, known as insulitis, is an important element in pathogenesis, other factors are necessary for disease initiation. Associations with variants of HLA and other genes related to immune system function, mainly haplotypes HLA-DR3-DQ2 and HLA-DR4-DQ8, are more evident. The influence of polymorphisms and epigenetic modifications, as well as the microbiome, is convincing proof of the existence of a complex interaction between genetic, immune, and environmental factors in the etiology and pathogenesis of this metabolic disorder. Loss of selftolerance to autoimmunity is a critical point in the development of the disease, and regulatory T cells play a key role in this process. Thus, any failure of these cells, either due to an insufficient number or altered expression of cytokines and transcription factors, may be the trigger for the onset of the disease. The protective action of regulatory T cells is controlled by gene expression that is modulated by epigenetic modifications, including the dysregulation of noncoding RNAs. This review takes an updated approach to the natural history of type 1 diabetes, focusing on the factors involved in the etiology and pathogenesis.

Asunto(s)

Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/genética , Haplotipos , Antígeno HLA-DR3/genética

RESUMEN

Löfgren's syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3-restricted manner. Using ELISPOT analysis, a greater number of IFN-γ- and IL-2-secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.

Asunto(s)

Aspergillus nidulans/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Epítopos de Linfocito T/inmunología , Sarcoidosis/inmunología , Adulto , Animales , Antígenos Fúngicos/inmunología , Estudios de Casos y Controles , Femenino , Proteínas Fúngicas/inmunología , Antígeno HLA-DR3/química , Antígeno HLA-DR3/genética , Antígeno HLA-DR3/inmunología , Humanos , Hibridomas/inmunología , Inmunoglobulina G , Masculino , Ratones Transgénicos , Persona de Mediana Edad

RESUMEN

INTRODUCTION: Neuromyelitis optica (NMO) and Multiple Sclerosis (MS) have been reported in different populations. NMO is more frequent in non-Caucasians, and clinical phenotype differences between populations are likely influenced by genetic susceptibility. In Brazil, it has been reported that NMO patients have a mainly European ancestry background. Like other autoimmune diseases, NMO has a multifactorial origin (i.e., genetics, environmental and infectious factors). Regarding the genetics of NMO, epidemiological findings suggest that a polygenic background has an important role in the development of this type of disease. In this context, various genes have been studied, such as those involved in the synthesis of the T cell beta chain receptor, the VH2-5 gene, myelin basic protein, the CTLA-4 gene, and the interleukin-1 gene. MATERIALS AND METHODS: We performed a study with the main objective of identifying candidate genes involved in the susceptibility to develop NMO in a Mexican population. RESULT: We included 35 patients with an NMO diagnosis according to the Wingerchuk 2006 criteria. The mean age of the patients was 43.3 years old (20-67), and 80 percent of the patients were women. The presence of HLA-DRB1*03 and HLA-DRB1*10 alleles were more frequent in NMO patients than in controls (n=198; p=0.03 and 0.005, respectively). CONCLUSION: There were no differences in the other alleles that have been described in MS subjects, such as HLA-DRB1*04, HLA-DRB1*08 and HLA-DRB1*13. These findings may support the hypothesis that implicated immune-genetics as a key factor in development of this type of disease.

Asunto(s)

Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Inmunoglobulina G/genética , Neuromielitis Óptica/etnología , Neuromielitis Óptica/genética , Adulto , Anciano , Etnicidad/genética , Femenino , Subtipos Serológicos HLA-DR/sangre , Subtipos Serológicos HLA-DR/genética , Antígeno HLA-DR3/sangre , Antígeno HLA-DR3/genética , Humanos , Inmunoglobulina G/sangre , Masculino , México/etnología , Persona de Mediana Edad , Neuromielitis Óptica/sangre , Adulto Joven

RESUMEN

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.

Asunto(s)

Cardiomiopatía Dilatada/genética , Antígeno HLA-DR3/genética , Biopsia , Cardiomiopatía Dilatada/patología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Miocardio/patología , Polimorfismo Genético , Factores de Riesgo

RESUMEN

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.

Asunto(s)

Humanos , Cardiomiopatía Dilatada/genética , Antígeno HLA-DR3/genética , Polimorfismo Genético , Biopsia , Cardiomiopatía Dilatada/patología , Estudios de Casos y Controles , Factores de Riesgo , Predisposición Genética a la Enfermedad , Miocardio/patología

RESUMEN

Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The -448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T > A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.

Asunto(s)

Autoanticuerpos/inmunología , Diabetes Mellitus Tipo 1/genética , Interleucinas/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Alelos , Autoanticuerpos/genética , Autoanticuerpos/metabolismo , Biomarcadores/metabolismo , Brasil , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Femenino , Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/inmunología , Antígeno HLA-DR3/genética , Antígeno HLA-DR3/inmunología , Antígeno HLA-DR4/genética , Antígeno HLA-DR4/inmunología , Humanos , Interleucinas/inmunología , Masculino , Regiones Promotoras Genéticas , Proteína Tirosina Fosfatasa no Receptora Tipo 22/inmunología , Riesgo , Análisis de Secuencia de ADN , Población Blanca

RESUMEN

Several studies correlated genetic background and pancreatic islet-cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and ß cell function. This characterization has a potential importance with regard to T1AD patients' stratification and follow-up in therapeutic prevention. In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1ß, tumour necrosis factor (TNF)-α, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0·80; P = 0·000), IL-8 and TNF-α (r = 0·60; P = 0·000); IL-8 and IL-12 (r = 0·57; P = 0·001) and TNF-α and IL-12 (r = 0·93; P = 0·000). Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = -0·45; P = 0·011) and CCL2 (r = -0·65; P = 0·000), while IA-2A showed a negative correlation with IL-10 (r = -0·38; P = 0·027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. In summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA-2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre-T1AD phase could help to explain the mechanistic of the well-known role of IA-2A as a more specific marker of beta-cell damage than GADA during the natural history of T1AD.

Asunto(s)

Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/inmunología , Glutamato Descarboxilasa/inmunología , Adolescente , Autoanticuerpos/inmunología , Quimiocinas/sangre , Niño , Citocinas/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Glutamato Descarboxilasa/genética , Antígeno HLA-DR3/genética , Antígeno HLA-DR4/genética , Humanos , Células Secretoras de Insulina/inmunología , Masculino , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética

RESUMEN

INTRODUCTION: Autoimmune hepatitis (AIH) and overlap-syndrome (OS) are autoimmune liver diseases of unknown etiology. Although HLA-DR3/DR4 plays a susceptibility role in AIH but there is limited information in regard to OS. OBJECTIVE: Determine the genetic expression of HLA-DR among patients with AIH versus OS in order to establish susceptibility alleles in comparison to healthy controls (HC). METHODS: 26 patients with AIH and 15 patients with OS were studied. Ninety-nine healthy historical controls without autoimmunity were evaluated. Patients with AIH and OS were selected based on the international group for the study of AIH criteria and the Chazouilleres criteria for OS. Patients had at least one liver biopsy. Characterization of HLA-DR was extracted from peripheral blood leukocytes. Alleles were obtained for AIH, OS and HC and comparisons were made between groups. RESULTS: There was a significant increase in HLADR3 and DR1 in AIH compared with the HC group (p = 0.04, OR 2.6, 0.87-7.9, 95% CI). In the AIH group there was a decreased frequency in allele HLA-DR8 when compared with HC (p = 0.04, OR 3.2). There were no statistical differences between the genetic frequencies in the OS group compared with HC. However, HLA-DR7 was able to distinguish between OS patients from those with AIH (p = 0.02, OR 9.8, 1.02-233.6, 95% CI). CONCLUSIONS: HLA-DR1/DR3 is increased in AIH, but contrary to data reported in AIH, HLA-DR7 frequency is increased in OS, suggesting increased susceptibility which distinguishes patients with AIH from those with OS.

Asunto(s)

Antígeno HLA-DR7/genética , Hepatitis Autoinmune/genética , Cirrosis Hepática Biliar/genética , Biopsia , Distribución de Chi-Cuadrado , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígeno HLA-DR1/genética , Antígeno HLA-DR3/genética , Hepatitis Autoinmune/clasificación , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/patología , Humanos , Hígado/inmunología , Hígado/patología , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/patología , México , Fenotipo , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo

RESUMEN

In this study, we aimed to compare the Mitsuda skin test with the alleles HLA-DR2/HLA-DR3 and HLA-DQ1, in relation to the clinical forms of leprosy in 176 patients (50 TT, 50 LL and 76 B). The results obtained did not reveal any association between the Mitsuda reaction and the HLA alleles in the clinical forms isolated. However, when analyzed according to Mitsuda test response, a significant association was found between patients with negative Mitsuda reaction and HLA-DQ1 (p=0.002). No association was observed between positive Mitsuda reaction and the HLA-DR2/DR3 alleles. We concluded that the allele HLA-DQ1 has an important participation when there is no response to the Mitsuda test. We suggest that more specific studies should be developed on this allele.

Asunto(s)

Antígenos HLA-D/inmunología , Lepra/inmunología , Pruebas Cutáneas/métodos , Alelos , Antígenos HLA-D/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/inmunología , Antígeno HLA-DR2/genética , Antígeno HLA-DR2/inmunología , Antígeno HLA-DR3/genética , Antígeno HLA-DR3/inmunología , Humanos , Fenotipo , Reacción en Cadena de la Polimerasa

RESUMEN

OBJECTIVE: The pathogenesis of sinonasal polyposis (SNP) is not clear; it has been suggested that it is polygenic and multifactorial. The major histocompatibility complex is a useful tool to predict genetic susceptibility to diseases, especially to autoimmune diseases. Since such susceptibility is influenced by ethnicity, it is necessary to have a wide knowledge of the structure of the population to which the patient belongs. The purpose of the study was to determine the association of HLA-DRB1 alleles with sinonasal polyposis in the Mexican Mestizo population. STUDY DESIGN: We studied the HLA-DR alleles in 34 adult Mexican Mestizo patients with SNP and compared them to those present in 99 healthy controls. METHODS: Genomic DNA from mononuclear cells was obtained by using the "salting out" technique and high-resolution DNA typing of the HLA-DRB1 alleles was performed after PCR amplification. RESULTS: We found a statistically significant increased frequency of the HLA-DRB1*03 allele (P = 0.03, odds ratio [OR] = 2.9, 95% confidence interval [CI]: 1.0-7.8) and of the HLA-DRB1*04 allele (P = 0.009, OR = 2.2, 95% CI: 1.2-4.2) in patients with SNP as compared to controls, and a statistically significant decreased frequency of the HLA-DRB1*08 allele (P = 0.01, OR = 0.2, 95% CI: 0.05-0.8). CONCLUSION: The HLA-DR locus seems to be associated with the genetic susceptibility to develop SNP in Mexicans. EBM RATING: B-2b.

Asunto(s)

ADN/genética , Expresión Génica , Antígeno HLA-DR3/genética , Antígeno HLA-DR4/genética , Pólipos Nasales , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Humanos , Incidencia , Masculino , México/etnología , Persona de Mediana Edad , Pólipos Nasales/etnología , Pólipos Nasales/genética , Pólipos Nasales/inmunología , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos

RESUMEN

We studied the human leukocytes antigens in 18 Egyptian children with biliary atresia (BA) without extrahepatic congenital malformations. There was a significant increased frequency of both B8 and DR3 (83.3% and 94.4% in patients with BA compared with 6.5% and 14.9% in the general population, respectively). Ten patients had the B8/DR3 haplotype. Our results support the hypothesis that genetic factors may play a role in susceptibility to BA.

Asunto(s)

Atresia Biliar/inmunología , Antígenos HLA/sangre , Atresia Biliar/genética , Estudios de Casos y Controles , Niño , Preescolar , Egipto/epidemiología , Femenino , Antígenos HLA/genética , Antígeno HLA-B8/sangre , Antígeno HLA-B8/genética , Antígeno HLA-DR3/sangre , Antígeno HLA-DR3/genética , Haplotipos , Humanos , Lactante , Masculino , Riesgo

RESUMEN

BACKGROUND/AIMS: Type 1 autoimmune hepatitis has a strong genetic predisposition that varies among different ethnic groups. Our aims were to determine if the clinical manifestations differed between patients with type 1 autoimmune hepatitis from Brazil and the United States and if classical disease could be associated with region-specific susceptibility markers. METHODS: The clinical manifestations and genetic risk factors of 161 patients from the United States were compared to those of 115 patients from Brazil. RESULTS: The patients from Brazil had earlier disease onset, lower frequency of concurrent immune diseases, higher serum levels of aspartate aminotransferase and gamma-globulin, greater occurrence of smooth muscle antibodies, and lower frequency of antinuclear antibodies than the patients from the United States. Human leukocyte antigen (HLA) DR13 and DRB1*1301 occurred more commonly in the Brazilian patients and HLA DR4 less often. Normal subjects from each country had similar frequencies of HLA DR13 and DR3. CONCLUSIONS: Type 1 autoimmune hepatitis in Brazil has different features at presentation than the disease in Caucasoid patients from the United States, and it is associated with HLA DR13. Background populations in each country have similar frequencies of HLA DR13 and DR3, and region-specific etiologic factors may determine the HLA association.

Asunto(s)

Hepatitis Autoinmune/epidemiología , Hepatitis Autoinmune/genética , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Antígenos HLA-DR/genética , Subtipos Serológicos HLA-DR , Antígeno HLA-DR3/genética , Cadenas HLA-DRB1 , Hepatitis Autoinmune/etiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiología

RESUMEN

OBJECTIVE: To determine the frequency of shared epitopes in our population of patients with rheumatoid arthritis (RA) and to investigate whether the presence of these alleles is associated with a more aggressive form of disease. METHODS: Demographic and clinical data were obtained from 140 patients with RA, 123 female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years. Radiographs of both hands were taken and scored by Larsen's method. HLA-DR alleles were determined by PCR-SSP. The control group comprised 202 healthy ethnic-matched subjects. RESULTS: DR4 was significantly more frequent in patients with RA than controls, and was observed in 70/140 patients (50%) versus 47/202 controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4 subtypes *0404 and *0401 were the most commonly found (37.7 and 29%, respectively). DR3 and DR11 exerted a protective effect with significantly higher frequency in controls than in patients with RA. When patients were divided into 2 groups according to disease severity (radiographic score) the frequency of alleles with QKRAA and QRRAA sequences was similar in both groups. Although with lower frequency, subtype *1001 alone was significantly more frequent in the severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03]. CONCLUSION: These results are in accordance with findings observed in Caucasians and differ from other Latin American populations. However shared epitope alleles failed to correlate with more severe disease with the exception of subtype *1001 which, although infrequent, was significantly more frequent in patients with relevant radiological damage.

Asunto(s)

Artritis Reumatoide/genética , Antígeno HLA-DR3/genética , Adulto , Anciano , Alelos , Argentina , Epítopos/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-DR/genética , Subtipos Serológicos HLA-DR , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad

RESUMEN

Predisposition to MS is associated with the HLA-DR2 antigen in white patients. The authors investigated the genetic factors behind the increasing frequency of MS in the Mexican population. HLA-DR and DQ were analyzed in 17 patients with MS, 15 of their first-degree relatives, and 99 healthy ethnically matched controls. DR2 or DR3 was found in 15 of 17 patients. In controls, both alleles had frequencies less than 0.05. MS in Mexican patients was associated with HLA-DR2 and DR3.

Asunto(s)

Antígenos de Histocompatibilidad Clase II/genética , Esclerosis Múltiple/genética , Adulto , Femenino , Genotipo , Antígeno HLA-DR2/genética , Antígeno HLA-DR3/genética , Humanos , Masculino , México , Persona de Mediana Edad , Linaje

RESUMEN

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is characterized by episodes of neuromuscular weakness occurring in the context of hypokalemia and hyperthyroidism and has been predominantly described in Oriental populations. Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of Native American descent. The objective was to analyze the clinical, biochemical, and HLA characteristics of a group of Mexican mestizo patients with TPP. METHODS: The sample was comprised of 14 men with TPP diagnosed since January 1990, based on one or more episodes of flaccid paralysis, accompanied by hypokalemia and occurring in the context of clinical and biochemical hyperthyroidism. Eight were available for HLA testing. RESULTS: Hyperthyroidism was diagnosed before the development of periodic paralysis in five of the patients, whereas in six it occurred afterward. The severity of paralysis did not correlate with the degree of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was found in Graves' patients without paralysis but not in those with paralysis, as compared to the general population. CONCLUSIONS: TPP is more common than previously thought in Mexicans, in whom it behaves as in other Native American groups. The lack of HLA-DR3 association in Graves' patients with TPP is interesting, but at the moment has no pathophysiological implications.

Asunto(s)

Etnicidad , Enfermedad de Graves/complicaciones , Antígenos HLA/análisis , Hipopotasemia/etnología , Parálisis/etnología , Tirotoxicosis/etnología , Adulto , Pueblo Asiatico/genética , Etnicidad/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Enfermedad de Graves/sangre , Enfermedad de Graves/inmunología , Antígenos HLA/genética , Antígeno HLA-DR3/análisis , Antígeno HLA-DR3/genética , Humanos , Hipopotasemia/sangre , Hipopotasemia/etiología , Hipopotasemia/inmunología , Indígenas Norteamericanos/genética , Masculino , México/epidemiología , Persona de Mediana Edad , Parálisis/sangre , Parálisis/etiología , Parálisis/inmunología , Periodicidad , Potasio/sangre , Factores Sexuales , España/etnología , Hormonas Tiroideas/sangre , Tirotoxicosis/sangre , Tirotoxicosis/etiología , Tirotoxicosis/inmunología , Población Blanca/genética

RESUMEN

A study performed on Venezuelans reveals a correlation between the common Caucasoid linkage group HLA-A1 B8 (A*0101, B*0801, DR3-) and increased lymphoproliferative activity stimulated by several concentrations of phytohemagglutin and concanavalin A in comparison to the group of persons possessing either the HLA-A1 (A*0101) antigen or the HLA-B8,DR3 (B*0801,DRB1*03012) haplotype. The increased lymphoproliferative activity was simultaneously present with increased CD16 cell counts and decreased CD3 and total mononuclear counts. A further comparison of lymphocyte population and subpopulation counts in peripheral blood and serum Ig G,A,M levels in the HLA-A1+ B8+ versus the HLA-A1-B8-high-responder individuals revealed increased CD16 cell counts and IgM levels in persons with the common Caucasoid haplotype (HLA-A1 B8). The data may suggest that some of the genes responsible for these levels or genes controlling their expression could be localized in or along the length of the common Caucasoid haplotype HLA-A1 B8 between the A and B loci of the MHC.

Asunto(s)

Formación de Anticuerpos/genética , Antígeno HLA-A1/genética , Antígeno HLA-B8/genética , Antígeno HLA-DR3/genética , Desequilibrio de Ligamiento , Población Blanca/genética , Adulto , Femenino , Haplotipos , Humanos , Masculino , Fenotipo , Receptores de IgG/análisis , Venezuela/etnología

RESUMEN

We studied IgG and IgM anticardiolipin antibodies (aCL) by an ELISA method in 80 Mexican systemic lupus erythematosus (SLE) patients and 378 of their first degree relatives. Sixty five percent of SLE patients and 16% of their relatives were positive for aCL. We also determined allele and haplotype frequencies of Major Histocompatibility Complex (MHC) genes (classes I, II and III) in both patients and relatives. MHC allele and haplotype frequencies of aCL positive and negative individuals were compared to those of normal ethnically matched controls. SLE patients with aCL had statistically significant increased corrected frequencies of HLA-DR3 (pC = 0.04, RR = 2.78); DR7 (pC = 0.005), RR = 3.42) and DQ2 (pC = 0.003, RR = 2.58) antigens. Their first degree relatives positive for aCL also had increased frequency of HLA-DR7 but it did not remain significant after correcting the P value. On the other hand, SLE patients negative for aCL had a moderate increased frequency of DR3 and DQ2 but not of DR7. These results suggest that DR7 associates with the presence of aCL. The distribution of MHC alleles in SLE patients positive for aCL resembles that found in their aCL positive first degree relatives. Since the presence of the antibody is not sufficient to predict a clinical outcome, we studied those patients with reliable clinical data regarding the presence of the antiphospholipid syndrome (aPLS). SLE patients with aPLS had significantly increased frequency of DR7 (pC = 0.004), as did those with probable aPLS (pC = 0.05), while the frequency of DR7 in SLE patients in the doubtful or negative aPLS categories was no different from normal controls. These data support a possible role of DR7 in the development of aCL in SLE patients and their relatives and suggest a contribution of this class II MHC antigen to the development of aPLS within SLE.

Asunto(s)

Anticuerpos Anticardiolipina/inmunología , Síndrome Antifosfolípido/inmunología , Antígeno HLA-DR7/inmunología , Lupus Eritematoso Sistémico/inmunología , Alelos , Síndrome Antifosfolípido/epidemiología , Síndrome Antifosfolípido/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Frecuencia de los Genes , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/inmunología , Antígeno HLA-DR3/genética , Antígeno HLA-DR3/inmunología , Antígeno HLA-DR7/genética , Haplotipos , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/genética , Masculino , México/epidemiología , Linaje

RESUMEN

The increase of HLA-DR3 and complotype SCO1 previously found in Mexican mestizo adults with E. histolytica amoebic abscess of the liver, was also found in Mexican mestizo children of either sex with the same disease, when compared to the healthy control population (adults and/or children) of the same ethnic and socioeconomic background. This HLA and complotype pattern was not found in Mexican Mestizo patients with amoebic rectocolitis. No linkage disequilibrium was found between these and the other MHC determinants tested in this survey. Thus, HLA-DR3 and SCO1 may constitute primary, independent risk factors, not for any kind of amoebic tissue invasion (i.e. amoebic rectocolitis), but specifically for amoebic liver abscess, irrespective of age or sex. The possibility of linkage disequilibrium with other factors (i.e. the TNF family) within or close to the MHC that were not tested in this study, is discussed. Children with amoebic liver abscess revealed a significant increase in HLA-DR5, and the absence of HLA-DR6 when compared to adults with amoebic liver abscess, suggesting that at least in this ethnic group these class II HLA traits may contribute to some of the peculiarities of pediatric amoebic liver abscess as opposed to the adult version of this disease. HLA-DR3, SCO1, but also HLA-DR5 and HLA-DR6 have all been associated with certain forms of immune-dysfunction, and may thus contribute to some of the clinical and immunological features of this parasitic disease.

Asunto(s)

Antígeno HLA-DR3 , Absceso Hepático Amebiano/inmunología , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Disentería Amebiana/genética , Disentería Amebiana/inmunología , Etnicidad/genética , Femenino , Frecuencia de los Genes , Antígeno HLA-DR3/genética , Antígeno HLA-DR5/genética , Antígeno HLA-DR6/genética , Humanos , Indígenas Norteamericanos/genética , Lactante , Desequilibrio de Ligamiento , Absceso Hepático Amebiano/genética , Masculino , México , Factores de Riesgo , Población Blanca/genética

Asunto(s)

Alelos , Tipificación y Pruebas Cruzadas Sanguíneas , Antígeno HLA-DR3/genética , Secuencia de Aminoácidos , Linfocitos B/química , Composición de Base , Secuencia de Bases , ADN Complementario , Humanos , México , Datos de Secuencia Molecular , Estados Unidos