RESUMO
Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10-36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.
Assuntos
Anoctaminas , Antígenos Nucleares do Vírus Epstein-Barr , Herpesvirus Humano 4 , Modelos Imunológicos , Mimetismo Molecular , Esclerose Múltipla , Anoctaminas/genética , Anoctaminas/imunologia , Autoanticorpos/imunologia , Reações Cruzadas/genética , Antígenos Nucleares do Vírus Epstein-Barr/genética , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Feminino , Antígeno HLA-A2/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Haplótipos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Fatores de RiscoRESUMO
AIM: We assessed an autoantibody against new gene expressed in prostate (NGEP) protein for prostate cancer (PCa) that may better diagnosis and prognosis approaches in the patients with PCa. METHODS: Autoantibodies against NGEP were measured in sera of PCa patients by ELISA. RESULTS: The autoantibody against NGEP is present in a significantly higher proportion in the sera of PCa patients as compared with healthy controls (p < 0.001). An inverse significant correlation was found between seropositive patients and Gleason score (p < 0.05) and serum prostate-specific antigen (recombinant NGEP; p < 0.05). CONCLUSION: The data showed that measurement of autoantibody against NGEP as a novel prostate-specific antigen in sera can be used as a potential biomarker to discriminate well-differentiated PCa patients from normal subjects.
