title: Sensitive and robust luminescent profiling of anti-La and other autoantibodies in Sjogren's syndrome.
abstract: Sjogren's syndrome (SjS) patients often have a variety of extraglandular manifestations including neurological and gastrointestinal involvement. In this study we evaluated the diagnostic performance of luciferase immunoprecipitation system (LIPS) that employs mammalian cell-produced recombinant antigens for analyzing SjS autoantibody responses. LIPS testing of mammalian cell-produced La, Ro60 and Ro52 recombinant antigens with defined commercial antibodies demonstrated highly specific immunoprecitation of each antigen without cross-reactivity. Next, sera from 57 SjS and 25 volunteers were evaluated by LIPS against a panel of human autoantigens. LIPS detected robust anti-La antibody levels in 43/57 SjS patients (75% sensitivity) and markedly outperformed an ELISA (46% sensitivity). Profiling of other SjS-associated autoantigens revealed the presence of anti-Ro60, anti-Ro52 in 63% and 61%, of SjS patients, respectively. Interestingly, a C-terminal fragment of Ro52 (Ro52-Delta2), a protein fragment not previously found to be antigenic by ELISA, also showed positive immunoreactivity in 42/57 SjS patients (65% sensitivity). Additional profiling of other autoantigens revealed that certain SjS patients also showed positive immunoreactivity with thyroid peroxidase (14%), AQP-4 (12%) and the H(+)/K(+) gastric ATPase (16%) suggesting potential autoantibody attack of thyroid, neuronal and gastric parietal cells, respectively. These heterogeneous autoantibody responses detected by LIPS in SjS will likely be useful for diagnosis and for evaluating extraglandular manifestations.
authors: Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. burbelop@nidcr.nih.gov
authors: Peter D
authors: PD
authors: Burbelo
authors: Hannah P
authors: HP
authors: Leahy
authors: Alexandra T
authors: AT
authors: Issa
authors: Sandra
authors: S
authors: Groot
authors: James N
authors: JN
authors: Baraniuk
authors: Nikolay P
authors: NP
authors: Nikolov
authors: Gabor G
authors: GG
authors: Illei
authors: Michael J
authors: MJ
authors: Iadarola
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology*; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D008156:Luciferases; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen