title: An Increased Diagnostic Sensitivity of Truncated GAD65 Autoantibodies in Type 1 Diabetes May Be Related to HLA-DQ8.
abstract: N-terminally truncated (96-585) GAD65 (tGAD65) autoantibodies may better delineate type 1 diabetes than full-length GAD65 (fGAD65) autoantibodies. We aimed to compare the diagnostic sensitivity and specificity between fGAD65 and tGAD65 autoantibodies for type 1 diabetes in relation to HLA-DQ. Sera from children and adolescents with newly diagnosed type 1 diabetes (n= 654) and healthy control subjects (n= 605) were analyzed in radiobinding assays for fGAD65 (fGADA), tGAD65 (tGADA), and commercial125I-GAD65 (RSRGADA) autoantibodies. The diagnostic sensitivity and specificity in the receiver operating characteristic curve did not differ between fGADA and tGADA. At the optimal cutoff, the diagnostic sensitivity for fGADA was lower than tGADA at similar diagnostic specificities. In 619 patients, 64% were positive for RSRGADA compared with 68% for fGADA and 74% for tGADA. Using non-DQ2/non-DQ8 patients as reference, the risk of being diagnosed with fGADA and tGADA was increased in patients with DQ2/2 and DQ2/8. Notably, logistic regression analysis suggested that DQ8/8 patients had an increased risk to be diagnosed with tGADA (P= 0.003) compared with fGADA (P= 0.09). tGADA had a higher diagnostic sensitivity for type 1 diabetes than both fGADA and RSRGADA. As DQ8/8 patients represent 10-11% of patients with newly diagnosed type 1 diabetes <18 years of age, tGADA analysis should prove useful for disease classification.
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden axel.wester.175@student.lu.se.
authors.forename: Axel
authors.initials: A
authors.lastname: Wester
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Skärstrand
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lind
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Anita
authors.initials: A
authors.lastname: Ramelius
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Carlsson
authors.affiliation: Department of Pediatrics, Ängelholm Hospital, Ängelholm, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cedervall
authors.affiliation: Department of Pediatrics, Ystad Hospital, Ystad, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Jönsson
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Sten A
authors.initials: SA
authors.lastname: Ivarsson
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Elding Larsson
authors.affiliation: Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Larsson
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindberg
authors.affiliation: Department of Pediatrics, Helsingborg Hospital, Helsingborg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Neiderud
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Fex
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Törn
authors.affiliation: Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D010446:Peptide Fragments / Q000276:immunology*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D010446:Peptide Fragments; C000602681:GAD65 (96-585); D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2