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Oligoclonal IgG bands : a persistent enigma

In 1948,  Kabat and his colleagues (Columbia University, New York) showed for the first time that immunoglobulins (i.e. the proteins which correspond to all our antibodies) increase in the cerebrospinal fluid of MS patients as well as of neurosyphilis patients. This observation classified multiple sclerosis definitively as an inflammatory and immune disease. In the early 1960s, Professors Lowenthal in Antwerp and Laterre in Louvain showed that the increase in the immunoglobulins content appeared as specific “oligoclonal bands”  in the cerebrospinal fluid despite not being present in the patient’s serum. The word “oligoclonal” was coined by Prof. Laterre and passed into international usage. In Greek, the meaning of oligo is “a few”, while clonal designates lymphocyte clones which have crossed the barrier between blood and cerebrospinal fluid and infiltrate the meninges and the central nervous system.

Antibody activity

At this point in time, we do not  know yet what is the antibody activity of most of these oligoclonal bands, or what, if any, may be their pathological role in the multiple-sclerosis process. We know that these bands are produced by cells known as plasma cells which are present in the meninges and brain, sometimes in the form of ectopic lymphoid follicles, never observed  in a normal brain. A minority of oligoclonal bands have an antibody activity against various neurotropic viruses such as measles, rubella, mumps, chickenpox/shingles, etc. However, the antibody activity of most oligoclonal bands remains unknown so far.

The chief interest of this anomaly is therefore the diagnosis of multiple sclerosis, as with the current technologies it is found in approximately 95 % of MS patients. Oligoclonal bands are present at the disease’s onset and generally persist throughout its progression. When the bands are present at the first clinical manifestation, they are  predictive  for a second attack leading to the diagnosis of “clinically definite multiple sclerosis”. Forms of MS without oligoclonal banding or with a very small number of bands are generally considered to be more benign and atrophy of the cerebral cortex is less. However, the presence of such bands is a predictive factor for a more rapid  evolution and a more severe disability.

Until now, existing treatments have not suppressed the presence of such oligoclonal bands. However, a very recent study has shown that in 24 MS patients treated with Tysabri, oligoclonal bands disappeared completely in 55 % of the cases and partly in 27 %. These results need to be confirmed on a larger number of patients.

Genetic factors

Finally, the synthesis of oligoclonal bands in the cerebrospinal fluid is dependent of genetic factors. This has just been demonstrated by the work of Prof. An Goris (KUL), which was partly supported  by the Charcot Foundation. The authors of this paper analysed 3026 samples of cerebrospinal fluid of worldwide provenance. This first analysis was repeated on 3891 further samples to confirm the results obtained from the first series. It appears that there is a highly significant correlation between the production of oligoclonal bands and two MS susceptibility genes, one  located on chromosome 6 and the other on chromosome 14. This research may enable the origin and above all the pathogenic activity of these oligoclonal bands, discovered over 50 years ago, to become better known.

Prof. Dr. Christian Sindic