title: Type 1 Diabetes at-risk children highly recognize Mycobacterium avium subspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin.
abstract: Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations. Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). A higher prevalence was detected for MAP/ZnT8 pairs (62,96% T1D vs. 7,14% HCs; p < 0.0001) compared to MAP/PI epitopes (22,22% T1D vs. 9,52% HCs) and decreasing trends were observed upon time-point analyses for most peptides. Similarly, classical ZnT8 Abs and GADA decreased in a time-dependent manner, whereas IAA titers increased by 12%. Responses in 0-9 year-old children were stronger than in 10-18 age group (75% vs. 69,1%; p < 0.04). Younger age, female sex and concomitant autoimmune disorders contributed to a stronger seroreactivity suggesting a possible implication of MAP in multiple autoimmune syndrome. Cross-reactivity of the homologous epitopes was reflected by a high correlation coefficient (r(2) > 0.8) and a pairwise overlap of positivity (>83% for MAP/ZnT8).
authors.affiliation: Università degli Studi di Sassari, Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, 07100 Sassari, Italy.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Niegowska
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Novella
authors.initials: N
authors.lastname: Rapini
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Piccinini
authors.affiliation: Università degli Studi di Sassari, Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, 07100 Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mameli
authors.affiliation: Università degli Studi di Sassari, Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, 07100 Sassari, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Caggiu
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Manca Bitti
authors.affiliation: Università degli Studi di Sassari, Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, 07100 Sassari, Italy.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001323:Autoantibodies / 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 / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011384:Proinsulin / Q000737:chemistry / Q000276:immunology*; D012307:Risk Factors; D000075703:Zinc Transporter 8
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001323:Autoantibodies; D027682:Cation Transport Proteins; D000939:Epitopes; D006680:HLA Antigens; D010455:Peptides; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D011384:Proinsulin