title: Elevated Serum GAD65 and GAD65-GADA Immune Complexes in Stiff Person Syndrome.
abstract: Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65 pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.
authors.affiliation: 1] Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden [2] Dept. of Genetics, Stanford University, CA 94305, USA.
authors.forename: Gucci Jijuan
authors.initials: GJ
authors.lastname: Gu Urban
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Friedman
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Ping
authors.initials: P
authors.lastname: Ren
authors.affiliation: Dept. of Clinical Sciences, Skåne University Hospital SUS, Lund University, Malmö, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Törn
authors.affiliation: Dept. of Clinical Sciences, Skåne University Hospital SUS, Lund University, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Fex
authors.affiliation: Dept. of Medicine, University of Washington, USA.
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hampe
authors.affiliation: Dept. of Clinical Sciences, Skåne University Hospital SUS, Lund University, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landegren
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Masood
authors.initials: M
authors.lastname: Kamali-Moghaddam
mesh_terms: D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D016750:Stiff-Person Syndrome / Q000097:blood* / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D010446:Peptide Fragments; C501056:glutamate decarboxylase 65 (202-221); D005968:Glutamate Decarboxylase