title: Detection of serum antibodies cross-reacting with Mycobacterium avium subspecies paratuberculosis and beta-cell antigen zinc transporter 8 homologous peptides in patients with high-risk proliferative diabetic retinopathy.
abstract: OBJECTIVE
  MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) cell membrane protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-cell membrane protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder.
  
  
  METHODS
  Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA.
  
  
  RESULTS
  Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼ 0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference (P = 0.016).
  
  
  CONCLUSIONS
  This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, Section of Ophthalmology, University of Sassari, Sassari, Italy; Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinna
authors.affiliation: Department of Biomedical Sciences, Section of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy.
authors.forename: Speranza
authors.initials: S
authors.lastname: Masala
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, Section of Ophthalmology, University of Sassari, Sassari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasetti
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, Section of Ophthalmology, University of Sassari, Sassari, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Maiore
authors.affiliation: Department of Biomedical Sciences, Section of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Cossu
authors.affiliation: Department of Biomedical Sciences, Section of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Paccagnini
authors.affiliation: Department of Biomedical Sciences, Section of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mameli
authors.affiliation: Department of Biomedical Sciences, Section of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000737:chemistry / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology / Q000473:pathology; D003930:Diabetic Retinopathy / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D016036:Seroepidemiologic Studies; D055815:Young Adult; D000075703:Zinc Transporter 8
chemical_list: D000907:Antibodies, Bacterial; D027682:Cation Transport Proteins; D000939:Epitopes; D010455:Peptides; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8