Rituximab for Anticytokine Autoantibody-Associated Syndromes

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Anti-cytokine autoantibodies have been shown to be an important mediator of certain serious diseases including immunodeificncy due to anti-IFNg autoantibodies and pulmonary alveolar proteinosis due to anti-GM-CSF autoantibodies. Some patients are refractory to optimized conventional therapy or have serious intolerance to standard approaches. We will be enrolling patients with anticytokine autoantibody syndromes who have have progressive disease despite optimized conventional treatment. We will treat patients and collect their blood and evaluate disease-affected regions however appropriate, i.e. imaging for anti-IFNg-autonantibody associated deep-seated infections, endoscopy for anti-IL-17-autoantibody-associated candidiasis, bronchoscopy or CT imaging for GM-CSF autoantibody associated pulmonary alveolar proteinosis. We will evaluate blood for changes in autoantibody levels using out luminex-based method for antibody screening, inflammatory markers using the clinical lab, and immunological parameters such as CD40 Ligand expression and B lymphocyte subsets using flow cytometry. We will also apherese patients prestudy and identify antigen-specific B cells (that recognize specific cytokines) by flow cytometry and ELIspot. We will also perform a quality of life survey pre and post study and clinically score disease activity to evaluate for evidence of efficacy. This study has been written and passed through the NIH IRB. We have garnered support from Genetech who will provide drug for the study as well as PK and PD data, and search for human anti-chimeric antibodies (HACAs). We have not yet enrolled patients to this study as it has just been activated by Genentech this month (8/2013).