Lupus: Open Access
Open Access

Abstract

Immunoadsorption in Buergers Disease (Thromboangiitis Obliterans): A Promising Therapeutic Option: Results of a Consecutive Patient Cohort Treated in Clinical Routine Care

Peter Klein-Weigel, Theresa Sophia Volz, Beate Gutsche-Petrak, Joana M. Boehnlein, Anne Bohlen, Siegrid Dreusicke, Jana Valerius, Marion Bimmler, Petra Hempel, Leonora Zange, Sebastian Schopp and Saban Elitok

Background: Buerger`s disease (TAO, thrombangiitis obliterans) is an inflammatory vessel disease affecting small and medium sized arteries and veins leading to acral or limb-threatening ischemia syndromes and/or thrombophlebitis with high amputation rates. Immunhistopatholocical and serological data let to the new paradigm of an immunopathogenesis of TAO. Based on this hypothesis immunadsorption (IA) was successfully introduced into the therapeutic spectrum and the presence of G-protein coupled autoantibodies in TAO and their successful elimination by IA was shown.

Objective: We present an update of the results of our observational cohort study including patients suffering from TAO consecutively treated by IA in clinical routine care.

Patients and methods: From December 2012 to February 2016 twenty-two patients suffering from TAO were treated with IA in our institution. Retrospectively, three patients had to be excluded (finding of an elevated Lp(a)- concentration, presence of atherosclerotic coronary lesions, loss of blood sample) leaving 19 patients for final analysis (17 male, 2 female; mean age 40 (20-54) years). IA was performed during a five-day course with Fesenius- GlobaffinR-adsorbers and an intended clearance of the 2.5-fold plasma volume. G-protein coupled -AAB were analyzed using specific commercially available ELISA techniques. Clinical follow-up included regular outpatient visits and/or telephone-contacts for patients living in more remote areas. Data is presented by descriptive statistics.

Results: G-protein receptor autoantibodies (AAB) were present in 14 of our patients (74%), with 1 AAB in 5 and multiple AAB in 9 patients. The presence of a clustering of AAB directed against the α1-receptor and endothelin Areceptor was seen in 9 out of the 14 AAB-positive patients (64%). AAB directed against ET-A-receptors never appeared without AAB directed against the α1-receptor and were exclusively directed against the extracellular receptor-loop 1. Immediately after a five day course of IA, 12 out of 14 AAB-positive patients were free of AAB (85%). Follow-up data was available in 15 patients. During a mean follow-up period of 3 month (0-35 month) there were no disease flairs. In all but one patient skin lesions healed. Pain scale values decreased from 7.0 (5-9) to 2.0 (0-5). Minor amputations already anticipated before IA were performed in two patients without complications. Only one patient underwent major-amputation after a failed surgical bypass procedure of doubtful indication with prior subcritical forefoot-tcpO2-values during follow-up in our institution. There was a high rate of smoking cessations (13 active smokers before IA, 3 during last follow-up) due to a close monitoring and admonition.

Conclusion: Although the exact rote of G-protein coupled receptor-AAB in TAO has yet to be defined, we were able to reproduce our formerly published results of a clustering of these AAB and their successful elimination by IA in this larger cohort, which anticipated a beneficial clinical course. IA might be able to stabilize the disease course, but the unusual high rate of smoking cessations made it impossible to exactly define its exact contribution on clinical outcome.