RESUMEN
Dermatitis herpetiformis (DH) and celiac disease (CD) are considered to be autoimmune diseases that share a specific trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not yet fully understood and no data are available regarding a possible role of fibroblasts in this disease. The aim of this study was to assess baseline DNA damage in fibroblasts in DH-diagnosed patients vs. fibroblasts of controls without DH or CD. Primary fibroblast cultures were derived from dermal biopsies from DH patients and controls (without DH or CD). In vitro genotoxic damage was investigated using the comet assay and ɣH2AX test after different treatments (with 33mer peptide and digested gliadin [DG]) in order to investigate a correlation between oxidative stress (evaluated by reactive oxygen species formation) and glutathione content. Our results demonstrate a difference in baseline DNA damage between cutaneous fibroblasts of controls and DH patients, moreover, DNA damage significantly increased after exposure to gluten (DG and 33mer peptide) in fibroblasts from DH patients. DNA damage in fibroblasts from patients under dapsone treatment was similar to that of the control group. Our data indicate that oxidative stress and DNA damage may be characteristics of fibroblasts from DH patients who are not treated with dapsone, particularly after exposure to gliadin peptides.
Asunto(s)
Enfermedad Celíaca/genética , Daño del ADN , Dermatitis Herpetiforme/genética , Fibroblastos/citología , Adulto , Anciano , Enfermedad Celíaca/inmunología , Ensayo Cometa , Dermatitis Herpetiforme/inmunología , Femenino , Gliadina/metabolismo , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Histonas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Itch which is one of the major, subjective symptoms in a course of bullous pemphigoid and dermatitis herpetiformis makes those two diseases totally different than other autoimmune blistering diseases. Its pathogenesis is still not fully known. The aim of this research was to assess the role of IL-31 in development of itch as well as to measure its intensity. Obtained results, as well as literature data, show that lower concentration of IL-31 in patients' serum may be correlated with its role in JAK/STAT signaling pathway which is involved in development of autoimmune blistering disease. Intensity of itch is surprisingly huge problem for the patients and the obtained results are comparable with results presented by atopic patients.
Asunto(s)
Dermatitis Herpetiforme/sangre , Interleucinas/sangre , Penfigoide Ampolloso/sangre , Prurito/sangre , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/fisiopatología , Dermatitis Herpetiforme/genética , Dermatitis Herpetiforme/fisiopatología , Femenino , Humanos , Interleucinas/genética , Quinasas Janus/genética , Masculino , Persona de Mediana Edad , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/fisiopatología , Prurito/genética , Prurito/fisiopatología , Factores de Transcripción STAT/genética , Transducción de SeñalAsunto(s)
Dermatitis Herpetiforme/genética , Predisposición Genética a la Enfermedad/epidemiología , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , Alelos , Estudios de Casos y Controles , China , Dermatitis Herpetiforme/etnología , Femenino , Humanos , Incidencia , Masculino , Valor Predictivo de las Pruebas , Sistema de Registros , Medición de RiesgoRESUMEN
We propose a biochemical mechanism for celiac disease and non-celiac gluten sensitivity that may rationalize many of the extradigestive disorders not explained by the current immunogenetic model. Our hypothesis is based on the homology between the 33-mer gliadin peptide and a component of the NMDA glutamate receptor ion channel - the human GRINA protein - using BLASTP software. Based on this homology the 33-mer may act as a natural antagonist interfering with the normal interactions of GRINA and its partners. The theory is supported by numerous independent data from the literature, and provides a mechanistic link with otherwise unrelated disorders, such as cleft lip and palate, thyroid dysfunction, restless legs syndrome, depression, ataxia, hearing loss, fibromyalgia, dermatitis herpetiformis, schizophrenia, toxoplasmosis, anemia, osteopenia, Fabry disease, Barret's adenocarcinoma, neuroblastoma, urinary incontinence, recurrent miscarriage, cardiac anomalies, reduced risk of breast cancer, stiff person syndrome, etc. The hypothesis also anticipates better animal models, and has the potential to open new avenues of research.
Asunto(s)
Enfermedad Celíaca/metabolismo , Gliadina/metabolismo , Modelos Genéticos , Receptores de N-Metil-D-Aspartato/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Secuencia de Aminoácidos , Animales , Ataxia/genética , Ataxia/metabolismo , Ataxia/patología , Enfermedades Óseas Metabólicas/genética , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/patología , Enfermedad Celíaca/inducido químicamente , Enfermedad Celíaca/genética , Enfermedad Celíaca/patología , Labio Leporino/genética , Labio Leporino/metabolismo , Labio Leporino/patología , Fisura del Paladar/genética , Fisura del Paladar/metabolismo , Fisura del Paladar/patología , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Dermatitis Herpetiforme/genética , Dermatitis Herpetiforme/metabolismo , Dermatitis Herpetiforme/patología , Regulación de la Expresión Génica , Gliadina/genética , Glútenes/efectos adversos , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Unión Proteica , Multimerización de Proteína , Proteínas/genética , Proteínas/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Homología de Secuencia de Aminoácido , Transducción de Señal , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Tiroiditis/genética , Tiroiditis/metabolismo , Tiroiditis/patología , TransactivadoresAsunto(s)
Enfermedad Celíaca/complicaciones , Dermatitis Herpetiforme/etiología , Adolescente , Adulto , Brasil , Enfermedad Celíaca/genética , Enfermedad Celíaca/patología , Dermatitis Herpetiforme/genética , Dermatitis Herpetiforme/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
We performed a genome-wide association study (GWAS) of 1550 North American celiac disease cases and 3084 controls. Twelve SNPs, distributed across four regions (3p21.31, 4q27, 6q15, 6q25), were significantly associated with disease (p-value <1.0×10-7), and a further seven SNPs, across four additional regions (1q24.3, 10p15.1, 6q22.31, 17q21.32) had suggestive evidence (1.0×10-7 < p-value < 1.0×10-6). This study replicated a previous suggestive association within FRMD4B (3p14.1), confirming it as a celiac disease locus. All four regions with significant associations and two regions with suggestive results (1q24.3, 10p15.1) were known disease loci. The 6q22.31 and 10p11.23 regions were not replicated. A total of 410 SNPs distributed across the eight significant and suggestive regions were tested for association with dermatitis herpetiformis and microscopic colitis. Preliminary, suggestive statistical evidence for association with the two traits was found at chromosomes 3p21.31, 6q15, 6q25, 1q24.3 and 10p11.23, with future studies being required to validate the reported associations.