Detection of intrathecal immunoglobulin G synthesis by capillary isoelectric focusing immunoassay in oligoclonal band negative multiple sclerosis

J Neurol. 2016 May;263(5):954-960. doi: 10.1007/s00415-016-8094-3. Epub 2016 Mar 19.


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.

Keywords: CIEF; Multiple sclerosis; OCB; Oligoclonal bands.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Electrophoresis, Capillary / methods*
  • Electrophoresis, Polyacrylamide Gel / methods
  • Humans
  • Immunoassay / methods
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid*
  • Isoelectric Focusing / methods*
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid*
  • Oligoclonal Bands / cerebrospinal fluid*


  • Immunoglobulin G
  • Oligoclonal Bands