MS Patients Positive for Oligoclonal Bands Have Greater Brain Atrophy
A new global brain MRI study shows that patients who test positive for oligoclonal bands have greater loss of white matter than MS patients lacking those bands. The results of the study suggest that there may be reason to consider MS patients without oligoclonal bands to be a clinically distinct subgroup.
Patients lacking oligoclonal bands (OCBs) have less overall brain atrophy than those who test positive for the bands, according to a new study published in the Journal of Neuroimmunology. The authors argue that OCB-negative patients should be considered a distinct subgroup of MS patients (Ferreira et al., 2014).
Oligoclonal bands are immunoglobulins that collect in a patient’s blood plasma or cerebrospinal fluid (CSF). The presence of OCBs in the CSF has often been used as a diagnostic criterion in MS. Though not every person with MS has OCBs, their presence is generally associated with a younger age of onset and a poorer disease outcome. According to the authors of the new study, most MRI studies of OCB-positive and -negative patients have focused only on the differences between brain lesions. Theirs, they say, is the first study to look at global CNS differences between these two subsets.
The researchers performed MRI scans on 28 OCB-negative and 35 OCB-positive patients with either relapsing-remitting MS or secondary progressive MS and matched them for disease activity. Overall, the OCB-positive patients had greater brain atrophy than the negatives, particularly in white matter areas (p = 0.029).
From there, the team looked at regions of the brain, using three different multivariate orthogonal projections to latent structures (OPLS) statistical models. Variables included age, gender, MRI protocol, disease course, age of onset, disease duration, treatment duration, and Expanded Disability Status Scale scores. The first two OPLS models looked at cortical and juxtacortical regions. The third OPLS model looked at subcortical structures (basal ganglia; diencephalon; hippocampus; amygdala; cerebellum; the corpus callosum; lateral, third, and fourth ventricles; and the periventricular and deep white matter).
The third model was the only one that reached statistical significance. In general, the researchers found that OCB-positive patients had the same amount of gray matter as OCB-negative patients, but that the positives had less white matter and greater CSF volume. At the regional level, the OCB-positive patients had less volume in the basal ganglia, diencephalon, cerebellum and hippocampus. In regional white matter areas, OCB-positive patients had greater volume loss in the corpus callosum, the periventricular-deep white matter, the brainstem, and the cerebellum white matter.
One possibility that could explain the difference, according to the researchers, is epitope expression. Perhaps OCB-negative patients have a different epitope expression than OCB-positive patients, arising from a different expression of HLA class II genes. They suggest that this difference would mean that OCB-negative patients represent a different subgroup of MS than OCB-positive patients. Of course, researchers could only confirm that with further studies with larger sample sizes.
If OCB-negative MS patients do belong in a distinct subgroup, that would have implications for treatment. The authors suggest that it’s possible that OCB-negative patients might have a different disease progression and different responses to DMTs, but no one has noticed this difference so far. It’s possible that the classification would also be relevant to the inclusion of OCB-negative patients in clinical trials.
Key open questions
- How should the characterization of OCB-negatives versus -positives be pursued further?
- If OCB-negative patients are indeed a subgroup of MS, how should that be included in the diagnostic criteria for all forms of MS?
Disclosures and sources of funding
Ferreira and his team received support from the Strategic Research Programme in Neuroscience at Karolinska Institutet, the Swedish Brain Power, the regional agreement on medical training in clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Erik and Edith Fernström Foundation for Medical Research, the Swedish Society of Medicine, and the Fundación Canaria Dr. Manuel Morales. They claim no competing interests.