RESUMO
Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LABD, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.
Assuntos
Biomarcadores , Dermatite Herpetiforme , Dermatose Linear Bolhosa por IgA , Proteoma , Humanos , Dermatite Herpetiforme/sangue , Dermatite Herpetiforme/diagnóstico , Dermatite Herpetiforme/imunologia , Biomarcadores/sangue , Feminino , Masculino , Adulto , Dermatose Linear Bolhosa por IgA/sangue , Dermatose Linear Bolhosa por IgA/diagnóstico , Pessoa de Meia-Idade , Diagnóstico Diferencial , Proteômica/métodos , Imunoglobulina A/sangue , Adolescente , Adulto Jovem , Idoso , CriançaAssuntos
Eritema Multiforme/sangue , Eritema Multiforme/diagnóstico , Imunoglobulina A/sangue , Dermatose Linear Bolhosa por IgA/sangue , Dermatose Linear Bolhosa por IgA/diagnóstico , Eritema Multiforme/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Dermatose Linear Bolhosa por IgA/tratamento farmacológico , Masculino , Adulto JovemRESUMO
A 60-year-old cachexic man visited the dermatology outpatient department with fluid-filled lesions on much of his body. He had an intermittent high-grade fever, diarrhea, and vomiting for the past 2 months associated with weight loss and decreased appetite. He admitted to having taken norfloxacin 400 mg twice daily for 3 days for diarrhea, 5 days prior to the onset of the lesions. Physical examination revealed pallor and significant lymphadenopathy (cervical, axillary, and inguinal), and his body mass index (BMI) was 17.67. There were generalized, bizarre-shaped, discrete, as well as coalescing, vesicles and bullae over a diffusely erythematous skin. Characteristic "string of pearls morphology" could be seen over the trunk (Figure 1A and 1B). The trunk exhibited sheets of skin peeling with underlying erosions and Nikolsky sign was positive (Figure 1C), although there was no cutaneous tenderness or mucosal involvement. A Tzanck smear revealed the presence of neutrophils and eosinophils but no acantholytic cells. There was moderate hepatomegaly (7 cm below the costal margins).
Assuntos
Anti-Infecciosos/efeitos adversos , Dermatose Linear Bolhosa por IgA/sangue , Dermatose Linear Bolhosa por IgA/diagnóstico , Norfloxacino/efeitos adversos , Anti-Infecciosos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Norfloxacino/uso terapêuticoAssuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Laminina/imunologia , Dermatose Linear Bolhosa por IgA/sangue , Colágenos não Fibrilares/imunologia , Idoso de 80 Anos ou mais , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Dermatose Linear Bolhosa por IgA/patologia , Masculino , Colágeno Tipo XVIIRESUMO
Vancomycin (VCM) is known to induce linear IgA bullous dermatosis (LAD). However, in contrast to conventional LAD, in which circulating IgA autoantibodies against basement membrane proteins are commonly detected, patient sera from VCM-induced LAD yields negative results in indirect immunofluorescence microscopy, and the targeted autoantigen remains undetermined. By using sera from a typical patient with VCM-induced LAD, we identified that co-incubation of sera with VCM resulted in linear IgA deposition at the basement membrane zone by indirect immunofluorescence. Patient sera reacted with the dermal side of 1 mol/L NaCl-split skin and with the recombinant noncollagenous (i.e., NC1) domain of type VII collagen by both immunoblot and ELISA in the presence of VCM. The investigation of an additional 13 patients with VCM-induced LAD showed that 10 out of the 14 sera (71.4%) reacted with the NC1 domain of type VII collagen by ELISA when spiked with VCM, whereas only 4 (28.6%) tested positive without it. The enhancement of reactivity to NC1 by VCM, as determined by optical density via ELISA, was observed in 10 out of the 14 sera (71.4%). These findings indicate that type VII collagen is a target autoantigen in VCM-induced LAD and that VCM mediates IgA autoreactivity against type VII collagen, providing an insight into mechanisms involved in drug-induced autoimmune disease.