title: Serological evaluation of possible exposure to Ljungan virus and related parechovirus in autoimmune (type 1) diabetes in children.
abstract: Exposure to Ljungan virus (LV) is implicated in the risk of autoimmune (type 1) diabetes but possible contribution by other parechoviruses is not ruled out. The aim was to compare children diagnosed with type 1 diabetes in 2005-2011 (n = 69) with healthy controls (n = 294), all from the Jämtland County in Sweden, using an exploratory suspension multiplex immunoassay for IgM and IgG against 26 peptides of LV, human parechoviruses (HPeV), Aichi virus and poliovirus in relation to a radiobinding assay (RBA) for antibodies against LV and InfluenzaA/H1N1pdm09. Islet autoantibodies and HLA-DQ genotypes were also determined. 1) All five LV-peptide antibodies correlated to each other (P < 0.001) in the suspension multiplex IgM- and IgG-antibody assay; 2) The LV-VP1_31-60-IgG correlated with insulin autoantibodies alone (P = 0.007) and in combination with HLA-DQ8 overall (P = 0.022) as well as with HLA-DQ 8/8 and 8/X subjects (P = 0.013); 3) RBA detected LV antibodies correlated with young age at diagnosis (P < 0.001) and with insulin autoantibodies (P < 0.001) especially in young HLA-DQ8 subjects (P = 0.004); 4) LV-peptide-VP1_31-60-IgG correlated to RBA LV antibodies (P = 0.009); 5) HPeV3-peptide-IgM and -IgG showed inter-peptide correlations (P < 0.001) but only HPeV3-VP1_1-30-IgG (P < 0.001) and VP1_95-124-IgG (P = 0.009) were related to RBA LV antibodies without relation to insulin autoantibody positivity (P = 0.072 and P = 0.486, respectively). Both exploratory suspension multiplex IgG to LV-peptide VP1_31-60 and RBA detected LV antibodies correlated with insulin autoantibodies and HLA-DQ8 suggesting possible role in type 1 diabetes. It remains to be determined if cross-reactivity or concomitant exposure to LV and HPeV3 contributes to the seroprevalence.
authors: Department of Paediatrics, Östersund Hospital, Östersund, Sweden; Department of Clinical Sciences, Skåne University Hospital, Lund University/CRC, Malmö, Sweden.
authors: A-L
authors: AL
authors: Nilsson
authors: F
authors: F
authors: Vaziri-Sani
authors: P
authors: P
authors: Broberg
authors: A
authors: A
authors: Elfaitouri
authors: R
authors: R
authors: Pipkorn
authors: J
authors: J
authors: Blomberg
authors: S-A
authors: SA
authors: Ivarsson
authors: H
authors: H
authors: Elding Larsson
authors: Å
authors: Å
authors: Lernmark
mesh_terms: D000293:Adolescent; D000483:Alleles; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007223:Infant; D008297:Male; D030061:Parechovirus / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010850:Picornaviridae Infections / Q000150:complications* / Q000453:epidemiology* / Q000276:immunology; D016036:Seroepidemiologic Studies; D013548:Sweden / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D001323:Autoantibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides
keywords: HLA-DQ; autoimmune disease; insulin autoantibodies; islet autoantibodies; picornavirus