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Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: A preliminary case series
BMC Neurology, 07/02/09

Fluge O et al. – Observations suggest that B-lymphocytes are involved in chronic fatigue syndrome (CFS) pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function.

Methods

Basis for this case series was the observation that a patient with CFS had unexpected, marked recovery of CFS symptoms lasting for 5 months during and after cytotoxic chemotherapy for Hodgkin's disease
Postulation was that the transient recovery could be related to MTX treatment, which induces immunomodulation in part through B-cell depletion
In a case series this patient and 2 additional CFS pts were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab

Results

All 3 had improvement of all CFS symptoms
Patients 1 and 2 had major amelioration from 6 wks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 wks after intervention
Symptomatic effect lasted until wks 16, 18 and 44, respectively
At relapse, all were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3)
Again, all 3 had marked symptom improvement, mimicking their first response
After new symptom recurrence, pts 1 and 2 were given weekly oral MTX, patient 1 having effect also from this agent
Pts 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit
No unexpected toxicity was seen

Exclusive Author Commentary
Oystein Fluge and Olav Mella, 07/06/09

This study of 3 pilot patients demonstrated that B-cell depletion resulted in marked, but transient, improvement of all CFS-related symptoms, indicating that at least a subset of CFS patients have their symptoms maintained through B-lymphocyte action, either directly or indirectly through other parts of the immune system. In addition to the impressive quality of life enhancement seen, thus pointing at a potential future drug treatment, the study turns focus toward the role of B-lymphocytes in this poorly understood entity and supports biological mechanisms as crucial for symptom development. As all perceptible, disease-related changes were ameliorated by the repeated drug interventions, a central mechanism seem to be touched by the manipulation and further biological studies may open way for understanding the underlying pathogenesis of CFS. Presently, a randomised, double-blinded study of 30 CFS patients is being performed to estimate the response rate to be expected from B-cell depletion in this, until now, merely symptom-based entity.

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