RESUMEN
A 76-year-old patient, since the age of 45, presented with frequent attacks often triggered by emotional stimuli and characterised by forward head drop and a fall to the ground without loss of consciousness. Clinically these episodes were misinterpreted as pseudoseizures and treated with clomipramine for more than 20 years. In spite of this chronic therapy, during the last year, the attacks presented with a daily recurrence and, moreover, after arbitrary clomipramine withdrawal, they increased in frequency until they became subcontinuous. Videopolygraphic analysis, multiple sleep latency test (MSLT) and human leukocyte antigen (HLA) association studies were suggestive of narcolepsy and the recurrent episodes, diagnosed as status cataplecticus, recovered after citalopram administration.
Asunto(s)
Cataplejía/diagnóstico , Errores Diagnósticos , Síncope/diagnóstico , Anciano , Electroencefalografía/métodos , Antígenos HLA-DQ/análisis , Cadenas beta de HLA-DQ , Antígeno HLA-DR2/análisis , Humanos , Imagen por Resonancia Magnética , Masculino , Recurrencia , Síncope/fisiopatologíaRESUMEN
We have reported previously that naive T cells from relapsing-remitting multiple sclerosis (RRMS) patients have T cell receptor (TCR) repertoire shifts, but the basis of these TCR repertoire shifts was uncertain. Here, we questioned whether RRMS patients have altered naive CD4 and CD8 T cell homeostasis by studying homeostatic proliferation and thymic production in RRMS patients and healthy controls. We measured thymic production by quantifying signal joint T cell receptor excision circles (sjTRECs). Both naive T subsets from controls showed an age-associated decrease in sjTRECs, i.e. evidence of progressive thymic involution, but we detected no age-associated decrease in sjTRECs in RRMS patients. Instead, naive CD8 T cells from patients had lower sjTRECs (P = 0.012) and higher Ki-67 proliferation levels (P = 0.04) than controls. Naive CD4 T cell sjTRECs did not differ between patients and controls. However, in RRMS these sjTRECs correlated strongly with CD31, a marker expressed by newly generated CD4 T cells but not by naive CD4 T cells that have undergone homeostatic proliferation. HLA-DR2 positivity correlated negatively with naive CD4 T cell CD31 expression in RRMS (P = 0.002). We conclude in RRMS that naive T subsets have homeostatic abnormalities due probably to peripheral (non-thymic) mechanisms. These abnormalities could have relevance for MS pathogenesis, as naive T cell changes may precede MS onset.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Homeostasis/inmunología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Timo/inmunología , División Celular/inmunología , Reordenamiento Génico de Linfocito T/genética , Reordenamiento Génico de Linfocito T/inmunología , Genes Codificadores de los Receptores de Linfocitos T/genética , Genes Codificadores de los Receptores de Linfocitos T/inmunología , Antígeno HLA-DR2/análisis , Homeostasis/genética , Humanos , Inmunofenotipificación/métodos , Antígeno Ki-67/análisis , Esclerosis Múltiple Recurrente-Remitente/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Receptores Inmunológicos/inmunología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: HLA-DR2 (15) and 14 (6) have been recently proposed as susceptibility alleles for the development of sarcoidosis and HLA-DR15 as a marker of poor outcome, but validation in other populations is necessary. METHODS: Employing serological techniques, we HLA-typed 103 Irish sarcoidosis patients and 105 ethnically-matched healthy controls for class I A and B and II DR and DQ alleles. RESULTS: HLA-B5 (10% vs. 2%, p = 0.018) and DR2 (45% vs. 27%, p = 0.007) were positively associated and B15 (0% vs. 7%, p = 0.01) negatively associated with sarcoidosis compared to control subjects. Seventy-five patients were followed > 2 years and 47 (63%) had chronic and 28 (37%) non-chronic disease. HLA-DR2 (55% vs. 27%, p = 0.001) and DR11 (26% vs. 5%, p<0.0001) were significantly more frequent in chronic disease vs. controls, in contrast to HLA-DR3 (13% vs. 38%, p = 0.002), which had a significant negative association. HLA-B5 (11% vs. 2%, p = 0.029) and DR3 (64% vs. 38%, p = 0.005) were significantly more frequent in non-chronic disease. Of the 29 patients achieving spontaneous remission, 24 (83%) were HLA-DR3 -positive and DR3-positivity was associated with significantly greater carbon monoxide diffusion at follow-up compared to DR3-negative patients (90% vs. 82% predicted, p = 0.027). CONCLUSIONS: This study supports the role of HLA-DR2 (15) as both a susceptibility and poor prognostic marker in sarcoidosis and DR2 positive patients may particularly benefit from close follow-up and early treatment. In contrast, DR3 positive patients are at a much lesser risk of chronic disease. Studies for long-term treatment effects require stratification for HLA-DR2 and DR3 status.
Asunto(s)
Biomarcadores/análisis , Antígeno HLA-DR2/análisis , Antígeno HLA-DR2/farmacología , Sarcoidosis/inmunología , Sarcoidosis/patología , Adulto , Monóxido de Carbono/sangre , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Pronóstico , Remisión Espontánea , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate whether there is an association between HLA class II and distal interphalangeal osteoarthritis (DIP OA). METHODS: The study group consisted of consecutive patients with and without DIP OA aged between 40 and 70 years. DIP OA was diagnosed by radiology. These patients were referred to an "Early Arthritis Clinic" (EAC) with different types of arthritis at an early stage. Patients with rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathies, and psoriatic arthritis were excluded for the purpose of this study. DNA typing for HLA-DR and x ray examination of the hands were performed at enrollment in the EAC. To establish whether the study group was representative of the Dutch population, a population based study in Zoetermeer (n=3243) for the prevalence of DIP OA and blood donors in the Leiden area (n=2400) for the HLA-DR antigen frequencies were used as references. RESULTS: Fifty five patients (33%) of the total study group (n=166) had DIP OA. The prevalence of DIP OA and frequency of the HLA-DR alleles were similar to those of the two reference groups. Within the study group an association between DIP OA and HLA-DR2 and DR4 with respectively odds ratios of 2.4 (95% confidence interval (CI) 1.1 to 5.0) and 0.3 (95% CI 0.1 to 0.7) was found. No association was found between other HLA-DR alleles and DIP OA. CONCLUSION: The study group is a representative sample of the Dutch population. The HLA-DR2 allele was more common in patients with DIP OA. Furthermore, an inverse relation was observed between DIP OA and HLA-DR4. The results confirm findings from other investigations implicating HLA-DR2 as a risk factor in the development of DIP OA.
Asunto(s)
Articulaciones de los Dedos , Genes MHC Clase II , Osteoartritis/genética , Adulto , Anciano , Alelos , Femenino , Articulaciones de los Dedos/diagnóstico por imagen , Antígeno HLA-DR2/análisis , Antígeno HLA-DR4/análisis , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Oportunidad Relativa , Osteoartritis/diagnóstico por imagen , Osteoartritis/epidemiología , Prevalencia , Estudios Prospectivos , RadiografíaRESUMEN
Previously we have reported an increased prevalence of migraine in narcoleptic patients. Because of the theoretical and clinical implications of this finding we recruited an independent new study sample of 100 patients with proven narcolepsy and conducted a structured 26-item interview based on the international diagnostic criteria for headache disorders, the Kiel Headache Questionnaire. Narcolepsy symptoms were measured by means of the Stanford Centre for Narcolepsy Sleep Inventory. Migraine prevalence was twofold to fourfold increased in the narcoleptic patients and amounted to 44.4% in women and 28.3% in men. The onset of narcolepsy symptoms was 12.3 +/- 11.4 years before the onset of migraine symptoms. The results might be regarded as indicative of a common pathophysiological pathway relevant to both of the two disorders.
Asunto(s)
Trastornos Migrañosos/epidemiología , Narcolepsia/epidemiología , Adulto , Anciano , Índice de Masa Corporal , Causalidad , Comorbilidad , Estudios Transversales , Femenino , Alemania/epidemiología , Antígeno HLA-DR2/análisis , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/etiología , Narcolepsia/etiología , MuestreoRESUMEN
The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having 'periodontitis as a manifestation of systemic diseases, associated with hematological disorders'. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram-negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram-positive cocci and Gram-positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family.
Asunto(s)
Periodontitis Agresiva/genética , Enfermedades Hematológicas/genética , Adulto , Periodontitis Agresiva/inmunología , Periodontitis Agresiva/microbiología , Campylobacter/crecimiento & desarrollo , Capnocytophaga/crecimiento & desarrollo , Quimiotaxis de Leucocito/inmunología , Niño , Preescolar , Femenino , Fusobacterium nucleatum/crecimiento & desarrollo , Antígenos HLA-DQ/análisis , Cadenas beta de HLA-DQ , Antígenos HLA-DR/análisis , Subtipos Serológicos HLA-DR , Antígeno HLA-DR2/análisis , Humanos , Leucocitos/inmunología , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/inmunología , Bolsa Periodontal/microbiología , Fagocitosis/inmunología , Fenotipo , Porphyromonas/crecimiento & desarrollo , Porphyromonas gingivalis/crecimiento & desarrollo , Prevotella/crecimiento & desarrollo , Prevotella intermedia/crecimiento & desarrollo , Treponema/crecimiento & desarrolloRESUMEN
The association of scleroderma and malignancy has been a source of controversy during recent years. Several mechanisms of interrelationship have been suggested in earlier reports. Recent long-term studies suggest an increased association-ratio of scleroderma and malignancy. However, the underlying mechanisms remain elusive. This paper reviews the mechanisms described in earlier studies and discusses their possible pathogenetic meaning for the interrelationship and the pathogenesis of scleroderma and neoplasia.
Asunto(s)
Antígeno HLA-DR2/análisis , Neoplasias/etiología , Esclerodermia Sistémica/etiología , Factores de Edad , Antibióticos Antineoplásicos/efectos adversos , Autoinmunidad , Bleomicina/efectos adversos , Neoplasias de la Mama/etiología , Citocinas/fisiología , Susceptibilidad a Enfermedades , Humanos , Inmunidad Celular , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Síndromes Paraneoplásicos/patología , Estudios Retrospectivos , Esclerodermia Sistémica/inducido químicamente , Serotonina/fisiología , Triptófano/fisiologíaRESUMEN
OBJECTIVE: To analyze the frequency of human leukocyte antigens class II-DR in children and adolescents with systemic lupus erythematosus. PATIENTS AND METHODS: Fifty-fiveBrazilian systemic lupus erythematosus children and adolescents and 308 healthy individuals were studied. Gender, race, and age of onset of systemic lupus erythematosus were recorded. The human leukocyte antigens typing of class II-DR was carried out by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). Data were analyzed statistically using the chi square test with Yates' correction, Fisher's exact test, and Bonferroni's correction. RESULTS: Human leukocyte antigen-DR 15 was the most frequently detected antigen in this group of children and adolescents, and it also occurred more frequently in the female group, in children with onset of systemic lupus erythematosus between 0 and 9 years and between 10 to 14 years, and in the Black race group, but these associations were not statistically significants. CONCLUSION: In this group of children and adolescents with a high degree of racial admixture, we could not verify a significant association between human leukocyte antigens class II-DR and systemic lupus erythematosus.
Asunto(s)
Antígeno HLA-DR2/genética , Lupus Eritematoso Sistémico/genética , Adolescente , Adulto , Edad de Inicio , Pueblo Asiatico/genética , Población Negra/genética , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígeno HLA-DR2/análisis , Humanos , Lupus Eritematoso Sistémico/inmunología , Masculino , Distribución por Sexo , Población Blanca/genéticaRESUMEN
We reported a 10-year-old boy with narcolepsy, the onset of which was at the age of 8 years and 6 months. The initial symptom was excessive daytime sleepiness, followed by cataplexy and disrupted nocturnal sleep. There was neither hallucination nor sleep paralysis. A daytime polysomnogram showed a sleep-onset rapid eye movement period (SOREMP), and human leukocyte antigen (HLA) analysis revealed HLA-DR2/DQB1 * 0602. Treatment with methylphenidate and clomipramine was effective; methylphenidate (30 mg/day) improved his wakefulness and alertness throughout the day, and clomipramine (20 mg/day) reduced the number of cataplexic episodes. Because of their abnormal behavior, prepubertal narcoleptic children may often be misdiagnosed as having epilepsy or an attention deficit hyperactivity disorder. Therefore, they need early diagnosis and treatment. Assistance should be provided to protect them from being labeled as lazy by their parents and school teachers.
Asunto(s)
Narcolepsia/diagnóstico , Niño , Clomipramina/uso terapéutico , Antígenos HLA-DQ/análisis , Cadenas beta de HLA-DQ , Antígeno HLA-DR2/análisis , Humanos , Masculino , Metilfenidato/uso terapéutico , Narcolepsia/tratamiento farmacológico , Narcolepsia/psicología , PolisomnografíaRESUMEN
Three patients, one woman aged 43, and two men aged 32 and 51, suffered from excessive daytime sleepiness with different causes. The woman experienced nocturnal motor attacks of epileptic origin, responding to carbamazepine. The diagnosis was based on polysomnographic recordings combined with video monitoring. Narcolepsy was diagnosed in the 32-year-old man. He also suffered from cataplexy. The diagnosis was supported by a multiple sleep latency test and HLA-DR2 positivity. He was treated with clomipramine. In the 43-year-old man an obstructive sleep apnoea syndrome was diagnosed by polysomnographic recording. He was treated successfully with continuous positive airway pressure. These patients show that excessive daytime sleepiness is sometimes difficult to recognise and can be a potentially incapacitating symptom of a treatable underlying disorder. Diagnosis is made by careful history taking and through the use of different types of somnographic recordings.
Asunto(s)
Trastornos de Somnolencia Excesiva/etiología , Narcolepsia/diagnóstico , Síndrome de Mioclonía Nocturna/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Adulto , Anticonvulsivantes/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Carbamazepina/uso terapéutico , Clomipramina/uso terapéutico , Diagnóstico Diferencial , Femenino , Antígeno HLA-DR2/análisis , Humanos , Masculino , Persona de Mediana Edad , Narcolepsia/complicaciones , Narcolepsia/tratamiento farmacológico , Síndrome de Mioclonía Nocturna/complicaciones , Síndrome de Mioclonía Nocturna/tratamiento farmacológico , Polisomnografía , Respiración con Presión Positiva , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapiaRESUMEN
Human leukocyte antigen (HLA) types were obtained from 79 Iranian patients with multiple sclerosis and compared with 100 controls. The prevalence of HLA-A24 (30.3% versus 18.0%), HLA-DR2 (43.0% versus 28. 0%) and HLA-DR15 (36.7% versus 23.0%) were significantly increased in multiple sclerosis patients compared with controls. However age at onset, and disease status (relapsing - remitting or primary progressive) did not show an association with any particular HLA type. Multiple Sclerosis (2000) 6 317 - 319
Asunto(s)
Antígenos HLA-A/análisis , Antígenos HLA-A/inmunología , Antígenos HLA-DR/análisis , Antígenos HLA-DR/inmunología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Adolescente , Adulto , Edad de Inicio , Linfocitos B/inmunología , Femenino , Predisposición Genética a la Enfermedad , Antígeno HLA-A24 , Subtipos Serológicos HLA-DR , Antígeno HLA-DR2/análisis , Antígeno HLA-DR2/inmunología , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/genéticaRESUMEN
Toxic oil syndrome (TOS) was an epidemic which broke out in Spain in 1981, caused by the ingestion of rapeseed oil denatured with 2% aniline and sold illegally as edible oil. More than 20,000 people were affected and mortality rate was 8.4%. Genetic susceptibility appears to be involved in the pathology of this disease. Several reports have described association between the chronic stage of the disease and DR-DQ antigens (DR3, DR4, DR2 and DQ8). In the present work, we have reassessed the HLA class II antigens in a well-designed case-control study. Triplets of subjects (n=265) composed by chronic patients (n=117), non-affected family members (n=71) and non-related controls (n=77) were studied. Also, HLA class II antigens were analyzed in patients who had died from TOS (n= 34) and in TOS control patients who died from other non-TOS related causes (n=13). Regarding surviving patients no significant association was found between HLA and disease. In contrast, an increase in phenotypic frequency of DR2 antigen, was found in patients who had died from TOS (73.5%) compared with the whole study group: TOS-affected alive patients (25.6%, corrected P<0.001), non-affected family members (28.5%, corrected P<0.001), non-related controls (23.9%, corrected P<0.001) and dead controls (38.4%, P=0.03).
Asunto(s)
Compuestos de Anilina/efectos adversos , Enfermedades Autoinmunes/inmunología , Brotes de Enfermedades , Antígeno HLA-DR2/análisis , Aceites de Plantas/efectos adversos , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/fisiopatología , Estudios de Casos y Controles , Enfermedad Crónica , Ácidos Grasos Monoinsaturados , Antígeno HLA-DR2/clasificación , Antígeno HLA-DR2/genética , Adhesión en Parafina , Aceite de Brassica napus , España/epidemiología , Sobrevivientes , SíndromeRESUMEN
In the present study we determined the frequencies of four haplotypes of the human T-cell lymphotropic virus-related endogenous sequence, HRES-1, in 110 multiple sclerosis (MS) patients and 100 healthy control subjects from the United Kingdom. We found evidence of an association between this endogenous retrovirus and MS (p < 0.01), in particular reflecting an increased frequency of HRES-1 haplotype 1 in the group of patients. There was no significant difference in the distribution of HRES-1 haplotypes between relapsing-remitting MS and the primary progressive form of the disease. The odds ratio for HRES-1 haplotype 1 and MS did not differ significantly between individuals positive for HLA-DR2 and DR2-negative individuals. Comparison of the observations from the present study with previous results implicated HRES-1 as a marker of genetic heterogeneity in MS.
Asunto(s)
Retrovirus Endógenos/aislamiento & purificación , Esclerosis Múltiple/virología , ADN Viral/aislamiento & purificación , Progresión de la Enfermedad , Retrovirus Endógenos/genética , Frecuencia de los Genes , Heterogeneidad Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Antígeno HLA-DR2/análisis , Haplotipos/genética , Humanos , Esclerosis Múltiple/clasificación , Esclerosis Múltiple/epidemiología , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Provirus/genética , Provirus/aislamiento & purificación , Reino Unido/epidemiologíaRESUMEN
The aim of this study was to analyze the association between HLA class I and class II DR frequency in the different stages of sarcoidosis in Polish population. 88 patients and 30 healthy controls have been typed. Patients were divided into three groups depending on radiological findings. In the first group were 28 cases presenting the regression of the disease. In the second were 33 patients in stable stage II or III and in the third group 27 patients with pulmonary fibrosis (stage IV). The typing was performed by NIH method using commercial sera. There were no statistically significant differences between studied group in HLA-A class I. The frequency of HLA B-18 was statistically more frequent in patients with sarcoidosis compared to healthy controls. HLA-DR1 was not present in third group of patients and the difference was significant compared to healthy controls.
Asunto(s)
Antígenos HLA/análisis , Antígeno HLA-DR2/análisis , Sarcoidosis/inmunología , Adulto , Frecuencia de los Genes , Antígenos HLA/genética , Antígenos HLA-B/análisis , Antígenos HLA-B/genética , Antígeno HLA-B18 , Antígeno HLA-DR1/análisis , Antígeno HLA-DR1/genética , Antígeno HLA-DR2/genética , Humanos , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/inmunología , Radiografía , Pruebas de Función Respiratoria , Sarcoidosis/clasificación , Sarcoidosis/diagnóstico por imagen , SerotipificaciónRESUMEN
We encountered two cases expressing excessive daytime sleepiness (EDS) and manifesting two or more sleep-onset rapid eye movement (REM) periods in the multiple sleep latency test. Unbearable daytime sleepiness occurred abruptly, which usually led to short-lasting naps, after which the patients felt refreshed. The EDS was successfully reduced by treatment with methylphenidate. In spite of these features similar to narcolepsy, these cases of REM hypersomnia did not present cataplexy or other auxiliary symptoms of narcolepsy, and, furthermore, the class-II human leukocyte antigen DR2 appeared to be negative.
Asunto(s)
Trastornos de Somnolencia Excesiva/diagnóstico , Antígeno HLA-DR2/análisis , Narcolepsia/diagnóstico , Adulto , Estimulantes del Sistema Nervioso Central/administración & dosificación , Ritmo Circadiano/efectos de los fármacos , Ritmo Circadiano/fisiología , Diagnóstico Diferencial , Trastornos de Somnolencia Excesiva/tratamiento farmacológico , Trastornos de Somnolencia Excesiva/fisiopatología , Electromiografía/efectos de los fármacos , Humanos , Masculino , Metilfenidato/administración & dosificación , Narcolepsia/tratamiento farmacológico , Narcolepsia/fisiopatología , Polisomnografía , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Sueño REM/efectos de los fármacos , Sueño REM/fisiologíaRESUMEN
An interaction between HLA antigens and predisposition to meningitis of specific and nonspecific etiology was studied in children and adolescents from an Azerbaijan population. The distribution of HLA antigens was found to be heterogeneous in the patients with meningitis of various etiology. Tuberculous meningitis was characterized by a significant rise in the detection rate of HLA-DR3 antigen, by a considerable frequency of B14 and DR2 antigens; patients with purulent meningitis much more significantly showed HLA-B12 antigen; in terms of locus A, there was an increase in the detection rates of HLA-A19 antigen in serous meningitis.
Asunto(s)
Antígenos HLA/análisis , Meningitis/inmunología , Adolescente , Azerbaiyán , Niño , Predisposición Genética a la Enfermedad , Antígenos HLA-A/análisis , Antígenos HLA-B/análisis , Antígeno HLA-B14 , Antígeno HLA-DR2/análisis , Antígeno HLA-DR3/análisis , Humanos , Meningitis/etiología , Meningitis/genética , Persona de Mediana Edad , Modelos Teóricos , Factores de Riesgo , Tuberculosis Meníngea/etiología , Tuberculosis Meníngea/genética , Tuberculosis Meníngea/inmunologíaRESUMEN
Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.
Asunto(s)
Diabetes Mellitus Tipo 1/congénito , Autoanticuerpos/sangre , Glucemia/análisis , Péptido C/metabolismo , Preescolar , Consanguinidad , Deshidratación/fisiopatología , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/fisiopatología , Cetoacidosis Diabética/diagnóstico , Diarrea/fisiopatología , Insuficiencia de Crecimiento/fisiopatología , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Fiebre/fisiopatología , Crecimiento , Antígeno HLA-DR2/análisis , Humanos , Hipertrigliceridemia/diagnóstico , Hipoglucemiantes/uso terapéutico , Incidencia , Lactante , Recién Nacido , Insulina/uso terapéutico , Islotes Pancreáticos/inmunología , Masculino , Omán/epidemiología , Prevalencia , Trastornos Respiratorios/fisiopatología , Fases del SueñoRESUMEN
Autoimmune mechanisms involving T-cell responses to (a) myelin autoantigen(s), such as myelin basic protein (MBP), are thought to contribute to the pathogenesis of multiple sclerosis (MS). Cytokines may play a central role in the regulation of the pathogenic autoimmune responses in MS and the mediation of tissue damage in the disease. To study the cytokine expression of myelin reactive T-cells in MS, we determined the cytokine mRNA levels in a panel of blood derived MBP-specific T-cell clones derived from MS patients (33 clones) and normal controls (21 clones), using a novel quantitative RT-PCR method. Our results demonstrate that MBP-specific T-cells, both from MS patients and control subjects, predominantly display a Th1- or Th0-like cytokine pattern. Although MS clones express higher levels of TNFalpha and IL-10 mRNA, these differences do not reach statistical significance. Interestingly, significantly increased TNFalpha and IFNgamma mRNA levels were observed among clones derived from HLA-DR2 positive versus HLA-DR2 negative MS patients. This HLA halpotype is known to be associated with MS. The high levels of TNFalpha and IFNgamma mRNA observed in MBP-reactive T-cell clones from MS patients indicate an important role of these cytokines in the disease process. Our data lend further support to the pathogenic role of MBP-reactive T-cells in MS.
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Citocinas/genética , Esclerosis Múltiple/inmunología , Proteína Básica de Mielina/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Autoantígenos/inmunología , Células Clonales/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Genes Codificadores de los Receptores de Linfocitos T/genética , Antígeno HLA-DR2/análisis , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
We report the case of a 45-year-old Caucasian woman suffering from ankylosing spondylitis and undifferentiated connective tissue disease in whom the prevailing clinical features were retinal vasculitis and inflammatory low back pain. HLA typing revealed the concomitant presence of B27 and DR2 antigens. We hypothesise that the uncommon coexistence of ankylosing spondylitis and connective tissue disease in the same patient could be due to the exceptional association of HLA- B27 with the DR2 antigen.
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Enfermedades del Tejido Conjuntivo/inmunología , Antígeno HLA-B27/análisis , Antígeno HLA-DR2/análisis , Espondilitis Anquilosante/inmunología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Radiografía , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico por imagenRESUMEN
We compared clinical and demographic features, MRI findings, and HLA profiles of 57 Japanese patients with multiple sclerosis (MS) between groups with and without oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF). Patients with the optic-spinal form of MS (OpS-MS) or acute transverse myelopathy (ATM), which are distinctive and relatively common in Japanese MS, were excluded in this study. The OCB-positive rate was only 56.1% (32/57) among these 57 'conventional' MS patients, of whom clinical features were similar to those of Western MS patients. The demographic features, clinical course, disability, and cerebral abnormalities seen on MRI were similar in the OCB-negative and OCB-positive patient groups. HLA-DR2 antigen, which has been confirmed to be associated with MS in many populations, was more common in the OCB-positive than in the OCB-negative and control groups. Furthermore, DR4 antigen was statistically more common in the OCB-negative patient group. These results raise the possibility that the presence of OCB is related to the immunogenetic background of the patient, and that there may be at least two subpopulations in Japanese patients with 'conventional' MS from the viewpoint of immunogenetics. In one subpopulations, MS is associated with the DR2 antigen, and shows a stronger humoral immune response in the CSF, while in the other MS is associated with DR4, which has a milder humoral response. Further investigations involving more patients are warranted.