title: Detection of intrathecal immunoglobulin G synthesis by capillary isoelectric focusing immunoassay in oligoclonal band negative multiple sclerosis.
abstract: Oligoclonal immunoglobulin G bands (OCBs) restricted to the cerebrospinal fluid indicate intrathecal inflammation. Using isoelectric focusing and immunoblotting, they are detected in about 95 % of patients with clinically definite multiple sclerosis (MS). To elucidate whether in the remaining 5 % OCBs are truly absent or alternatively missed due to insufficient sensitivity of the routine measurement, we employed a new, highly sensitive nanoscale method for OCB detection. Capillary isoelectric focusing followed by immunological detection served to analyze OCBs in 33 well-characterized OCB-negative and 10 OCB-positive MS patients as well as in 100 OCB-negative control patients with non-inflammatory neurological diseases and 30 OCB-positive control patients with inflammatory neurological diseases. We detected intrathecal immunoglobulin G production in 10 out of 33 MS patients (30 %), initially diagnosed as being OCB-negative, and in all 10 OCB-positive MS patients, but in only 3 out of 100 non-inflammatory neurological controls (3 %) and in 29 of 30 inflammatory neurological controls (97 %). At least about one-third of MS patients without intrathecal immunoglobulin G synthesis according to standard methods are OCB-positive. Advanced methods for OCB detection may increase the analytical sensitivity for detecting OCB in patients with MS who are OCB-negative according to current routine methods.
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Halbgebauer
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Huss
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Buttmann
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Steinacker
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Oeckl
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Brecht
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weishaupt
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany. markus.otto@uni-ulm.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019075:Electrophoresis, Capillary / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid*; D007525:Isoelectric Focusing / Q000379:methods*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*
chemical_list: D007074:Immunoglobulin G; D043025:Oligoclonal Bands
keywords: CIEF; Multiple sclerosis; OCB; Oligoclonal bands