The news coming out of Norway this week regarding phase II clinical trials for treatment of CFS symptoms with Rituximab is certainly encouraging. I would add that the apparent success of this approach might not be all that surprising.
As mentioned by the authors, Rituximab is a B-cell suppressor used in the treatment of Hodgkin’s lymphoma. Abnormal B cell activity has long been suspected as playing a key role in CFS. As early as 2006, Maes and colleagues, in one of several related works, presented evidence of increased IgM antibodies directed specifically at cellular products of oxidative and nitrosative stress. The same year, our work with Dr. Suzanne Vernon and her colleagues also produced evidence of sustained oxidative stress in circulating immune cells based on their gene expression.
Figuren viser tre potensielle muligheter for Rituximab indusert B-celle deplesjon. A: Via komplementsystemet, B: Via makrofager eliminerer B-cellen via FcgammaR/CR eller ADCC og eller C: Ved at NK celler direkte angriper B-cellen og medfører celledød.
The immune system is also the body’s maintenance and clean-up crew, so it is not outlandish to think that a corresponding immune response would be mounted to recycle these cellular products. Coincidentally, Epstein-Barr virus (EBV) among other viral pathogens is a known promoter of oxidative stress and this pathogen alters B cell status through this and other means. Once subjugated, B-lymphocytes also serve as a reservoir for sustained latent infection in EBV.
Consistent with this, evidence of altered status in the B-lymphocytes of CFS patients was found in a study of gene expression conducted by our group in collaboration with the CFIDS Association of America with Dr. Vernon as a co-author. Further work supported by the Association and the National Institutes of Health conducted with Drs. Nancy Klimas and Mary Ann Fletcher of the University of Miami documented immune signaling patterns suggestive of an over-active Th2 or B-cell mediated immune response in a cohort of 50 female CFS patients. Both of these studies were cited in the report published by the Norwegian team.
In a nutshell, these positive clinical trial results are not only welcome but they represent a logical continuation of a line of investigation that has been ongoing. Although significant symptom relief was obtained in a majority of patients (2 out of 3), it is important to note that not all patients were responsive to treatment. This once again highlights the heterogeneous nature of this patient population and the need for better sub-typing. Nonetheless, these remain very encouraging results and they support the next step of investigation, namely that of validation in a set of larger clinical trials.
Dr. Gordon Broderick is an associate professor of pulmonary medicine in the department of medicine and a member of the faculty of medicine and dentistry at the University of Alberta. He serves as a member of the CFIDS Association’s Scientific Advisory Board.