title: G-protein coupled receptor auto-antibodies in thromboangiitis obliterans (Buerger's disease) and their removal by immunoadsorption.
abstract: BACKGROUND
  Immunhistopathological and serological data favors an immunopathogenesis of thromboangiitis onliterans (TAO, Buerger's disease). Auto antbodies seem to play a major role. Immunoadsorption (IA) proved to be therapeutically effective. We focused on agonistic autoantibodies (agAAB) directed against G-protein coupled receptors (GPCR) and proved the hypothesis, that these agAAB might be present in TAO and that a five day course of IA might be able to eliminate these agAAB effectively.
  
  
  METHODS
  Between December 2012 and May 2014 11 TAO-patients were treated by IA in a five day course. AgAAB-analysis was performed using specific ELISA techniques.
  
  
  RESULTS
  AgAAB were detected in 9 out of 11 patients (81.8 %).Multiple agAAB were present in 7 patients (63.6 %). A clustering of agAAB directed against loop1 of the adrenergic α1-receptor and the endothelin-A-(ETA)receptor was identified, representing 72.7 % resp. 54.5 % of the patients. AgAAB directed against the angiotensin-1 (AT-1) epitope 1 or 2 were detected in 3 patients and agAAB directed against protease-activated receptor (PAR) loop1/2 were seen in 2 patients. AgAAB directed against ETA-receptor loop1 never appeared without agAAB directed against α1-receptor loop1. Immediately after a five day-course of IA agAAB were absent in 81.8 % of the total study group and in 77.8 % of all cases tested positive for agAAB before IA.
  
  
  CONCLUSIONS
  AgAAB directed against GPCR were identified in TAO patients with a clustering of agAAB directed against α-1-adrenergic receptor loop1 and ETA-receptor loop1. AgAA were eliminated by IA in the majority of cases. We suggest that these agAA play an important role in the pathogenesis of TAO and that their elimination might be responsible for the positive therapeutic effects reported in patients treated with IA.
authors.affiliation: HELIOS Klinikum Berlin-Buch, Klinik für Angiologie, Germany.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Klein-Weigel
authors.affiliation: E.R.D.E.-AKK-Diagnostik GmbH, Berlin, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Bimmler
authors.affiliation: E.R.D.E.-AKK-Diagnostik GmbH, Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Hempel
authors.affiliation: Klinik für Kardiologie und Nephrologie, HELIOS Klinikum Berlin-Buch, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schöpp
authors.affiliation: HELIOS Klinikum Berlin-Buch, Klinik für Angiologie, Germany.
authors.forename: Siegrid
authors.initials: S
authors.lastname: Dreusicke
authors.affiliation: HELIOS Klinikum Berlin-Buch, Klinik für Angiologie, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Valerius
authors.affiliation: HELIOS Klinikum Berlin-Buch, Klinik für Angiologie, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Bohlen
authors.affiliation: HELIOS Klinikum Berlin-Buch, Klinik für Angiologie, Germany.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Boehnlein
authors.affiliation: Klinik für Allgemeine Innere Medizin und Gastroenterologie, HELIOS Klinikum Berlin-Buch, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bestler
authors.affiliation: Klinik für Kardiologie und Nephrologie, HELIOS Klinikum Berlin-Buch, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Funk
authors.affiliation: Klinik für Kardiologie und Nephrologie, HELIOS Klinikum Berlin-Buch, Germany.
authors.forename: Saban
authors.initials: S
authors.lastname: Elitok
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D016060:Sorption Detoxification; D013919:Thromboangiitis Obliterans / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D043562:Receptors, G-Protein-Coupled
keywords: Thromboangiitis obliterans; autoantibodies; buergers disease; g-protein coupled receptor; immunoadsorption