Journal of IiMER Volume 10 Issue 1 IIMEC11 June 2016 PRESENTERS Use of Rituximab: Before the use of rituximab, the strongest accepted evidence for an association between B-cells and systemic autoimmune diseases such as lupus and rheumatoid arthritis, was that clinical disease was associated with serum autoantibodies. The ability to remove B-cells with rituximab (given in 2 injections 1 week apart) has revealed factors that are important for both inducing remission and resumption of symptoms. Firstly, we found that our patients with high levels of autoantibodies had a significantly more pronounced and predictable clinical response to rituximab than patients with no autoantibodies. Secondly, B cells are killed very quickly by Rituximab – within a week of the infusions - but the kinetics of the clinical response (taking from 1- 5 months after depletion), suggest that it is a constantly generated B-cell product (?autoantibody) and not B-cells themselves that need to be reduced for remission to occur. Thirdly, a considerable proportion of B cells are not depleted, being resident in protective niches in lymphoid and inflamed tissues, and autoantibody levels can often remain raised, in the presence of considerable improvement of clinical symptoms. Taken together, this would suggest that only a proportion of parent B cells and autoantibodies are actually directly ‘pathogenic’. However, as patients eventually do relapse, the autoimmune response underlying the pathogenesis of disease must be self-sustaining. Patients are thus not ‘cured’ by Rituximab and symptoms can worsen again when the peripheral B cell compartment begins regenerating (6-9 months after infusion of rituximab), although some patients can have extended remission even after B cell return. Side-effects are rare and although reductions in serum total antibody levels can occur, effects on protective immunity are mild and serious infections rare. We have therefore learned much about how rituximab works in autoimmune rheumatic diseases but in ME/CFS patients, we are just beginning. As ME/CFS is such a heterogenous disease, our research is focussed on investigating B cell biology in these patients in order to qualify differences from healthy individuals and thus to identify those patients most likely to respond to rituximab and related therapies. B cell Research into ME/CFS: Fatigue is a major component of many systemic autoimmune rheumatic diseases where it is usually associated with the presence of inflammation and cytokine production. After rituximab, a marked reduction in fatigue indices has been reported, possibly due to reducing cytokine (usually interferon-α) production through removal of activating autoantibody containing immune complexes. The fatigue and other symptoms experienced by patients with ME/CFS differs in that no frank inflammatory site has been identified and the fatigue and other symptoms seems to be induced by both physical and mental stressors. We have hypothesized that dysregulation of metabolic re-programming in B cells may influence normal differentiation to appropriate (?Auto?) antibody secretion and memory B cell generation. Rituximab would therefore work by stopping the production of as yet only tentatively identified pathogenic antibodies. Following on from our already published data on B cells which showed that a certain marker, Invest in ME (Charity Nr. 1114035) www.investinme.org Page 63 of 77

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