Antibodies to Heteromeric Glycolipid Complexes in Guillain-Barré Syndrome.docVIP

Antibodies to Heteromeric Glycolipid Complexes in Guillain-Barré Syndrome Simon Rinaldi1*?, Kathryn M. Brennan1?, Gabriela Kalna2 3 3 , Christa Walgaard , Pieter van Doorn , Bart C. 3,4 5 Jacobs , Robert K. Yu , Jan-Eric Mansson 6 1 1 , Carl S. Goodyear , Hugh J. Willison 1 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom, 2 Bioinformatics, Beatson Institute for Cancer Research, Glasgow, United Kingdom, 3 Department of Neurology, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands, 4 Department of Immunology, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands, 5 Institute of Molecular Medicine and Genetics, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia, United States of America, 6 Laboratory Medicine/Clinical Chemistry, Sahlgrens University Hospital, Molndal, Sweden Abstract Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 h