RESUMEN
Several lines of evidence show that autoimmune responses evolving in type 1 diabetes (T1D) patients include the generation of multi-reactive autoantibody (AutoAb) repertoires, but their role in T1D pathogenesis remains elusive. We tested the hypothesis that variants at the immunoglobulin heavy chain (IGH) locus are genetic determinants of AutoAbs against pancreatic antigens and contribute to T1D susceptibility. With this aim, two independent study designs were used: a case-control study and a family-based cohort comprising a total of 240 T1D patients, 172 first-degree relatives (mother and/or father), and 130 unrelated healthy controls living in Portugal. We found that three SNPs in the IGH locus show suggestive association with T1D with the highest nominal association at rs1950942 (in the IGHM-IGHJ gene region) in both the case-control study (P = 9.35E-03) and the family-based cohort (P = 3.08E-03). These SNPs were also associated with IgG AutoAbs against pancreatic antigens and with AutoAb multi-reactivity in T1D patients. Notably, we found that the SNP with the highest association with T1D susceptibility and IgG autoantibody reactivity (rs1950942) was also associated with anti-GAD IgM reactivity in T1D patients (P = 5.98E-03) and in non-affected parents (P = 4.17E-03). This finding implies that IGH association with autoreactive IgM is detectable irrespective of disease status.These results suggest that genetic variants at the IgM gene region of the IGH locus contribute to antibody autoreactivity and are associated with T1D. We propose that the control of autoantibody generation by IGH polymorphisms is a component of the complex architecture of T1D genetic susceptibility.
Asunto(s)
Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Inmunoglobulina M/genética , Inmunoglobulina M/inmunología , Adolescente , Adulto , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus Tipo 1/sangre , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Antecedentes. Los pacientes diabéticos son especialmente vulnerables a las micosis debido a las modificaciones inducidas por la enfermedad en su sistema inmunitario. Estas modificaciones comprometen los sistemas de defensa naturales, como la piel y las uñas, sobre todo en las extremidades inferiores. Objetivos. Evaluar la presencia de dermatomicosis en los miembros inferiores de pacientes diabéticos portugueses seguidos en consultas de podología y determinar los posibles factores predisponentes y las especies de hongos más frecuentes asociadas a los casos incluidos en el estudio. Métodos. Se realizó un estudio prospectivo de seis meses de duración en 163 pacientes diabéticos con signos y síntomas de dermatomicosis, atendidos por el servicio de podología de la Asociación Portuguesa de Diabetes en Lisboa. Se obtuvieron muestras de piel y/o de uñas de las extremidades inferiores y se registraron los datos demográficos y clínicos de los pacientes. Resultados. Trichophyton rubrum fue el dermatofito más frecuentemente aislado (12,1%), seguido por Trichophyton mentagrophytes (7,7%) y Trichophyton tonsurans (4,4%). En el presente estudio ha quedado demostrada la asociación entre la diabetes de tipo 2 y la presencia de dermatomicosis en la población estudiada (p=0,013); y así mismo entre la incidencia de dermatomicosis y la localización de la lesión corporal (p=0,000). Para ningún otro factor predisponente analizado se identificó una asociación positiva con la infección (p > 0,05). Conclusiones. En Portugal apenas se dispone de datos sobre micosis superficiales en pacientes diabéticos. El presente estudio proporciona información sobre la caracterización de las dermatomicosis en miembros inferiores de estos pacientes(AU)
Background. Diabetic patients are particularly susceptible to fungal infections due to modifications that occur in their immunological system. These modifications compromise natural defences, such as skin and nails, especially from lower limbs. Aims. Assessing the presence of dermatomycosis in lower limbs of Portuguese diabetic patients followed on Podiatry consultation. Determination of possible predisposing factors and the most frequent fungal species associated with the cases are included in the study. Methods. A six-month prospective study was carried out in 163 diabetic patients with signs and symptoms of dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in Lisbon. Samples from the skin and/or nails of the lower limbs were collected and demographic and clinical data of those patients were recorded. Results. Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%), followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%). Our study showed positive associations between type 2 diabetes and the presence of dermatomycosis in the studied population (p=0.013); this association was also shown between the occurrence of dermatomycosis and the localization of the body lesion (p=0.000). No other predisposing factor tested was positively associated with infection (p>0.05). Conclusions. Data on superficial fungal infections in diabetic patients are scarce in Portugal. This study provides information on the characterization of dermatomycosis in lower limbs of diabetic patients(AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Dermatomicosis/complicaciones , Dermatomicosis/diagnóstico , Dermatomicosis/tratamiento farmacológico , Podiatría/métodos , Podiatría/tendencias , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/diagnóstico , Trichophyton/aislamiento & purificación , Dermatomicosis/fisiopatología , Enfermedades del Pie/complicaciones , Enfermedades del Pie/terapia , Extremidad Inferior/patología , Estudios ProspectivosRESUMEN
BACKGROUND: Diabetic patients are particularly susceptible to fungal infections due to modifications that occur in their immunological system. These modifications compromise natural defences, such as skin and nails, especially from lower limbs. AIMS: Assessing the presence of dermatomycosis in lower limbs of Portuguese diabetic patients followed on Podiatry consultation. Determination of possible predisposing factors and the most frequent fungal species associated with the cases are included in the study. METHODS: A six-month prospective study was carried out in 163 diabetic patients with signs and symptoms of dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in Lisbon. Samples from the skin and/or nails of the lower limbs were collected and demographic and clinical data of those patients were recorded. RESULTS: Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%), followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%). Our study showed positive associations between type 2 diabetes and the presence of dermatomycosis in the studied population (p=0.013); this association was also shown between the occurrence of dermatomycosis and the localization of the body lesion (p=0.000). No other predisposing factor tested was positively associated with infection (p>0.05). CONCLUSIONS: Data on superficial fungal infections in diabetic patients are scarce in Portugal. This study provides information on the characterization of dermatomycosis in lower limbs of diabetic patients.