CD19 B Cell Depletion in ME/CFS

Dr. Judith Bellmann-Strobl reported on CD19 B-cell depletion as a targeted approach for an autoimmune subgroup of ME/CFS. She summarised observations supporting autoimmunity in a subset of patients, including frequent post-infectious onset, female predominance, and functional autoantibodies against G protein-coupled receptors (GPCR autoantibodies) in around 20–30% of affected individuals, which may contribute to autonomic and vascular dysfunction as well as exercise intolerance and post-exertional malaise. She also referred to immune dysregulation with altered cytokine profiles and B-cell abnormalities, including activated memory and double-negative B-cell populations. As translational evidence, she noted that immunoadsorption can improve symptoms in subsets of patients and reduces circulating immunoglobulins and GPCR autoantibodies, while stressing that immunoadsorption is used as a proof-of-concept for patient selection. Building on this, she described a case series of three highly selected patients with post-infectious ME/CFS who were GPCR-autoantibody positive and had previously improved after immunoadsorption but later deteriorated again. All three received inebilizumab (300 mg i.v.), a CD19-depleting monoclonal antibody, and showed clinical improvement. Treatment was well tolerated, with no infusion-related adverse events or severe infections observed, and effects persisted for at least six months. She also highlighted that perceived fatigue severity did not necessarily correlate with functional status, underscoring the need for robust outcome measures. Bellmann-Strobl concluded by outlining the planned PIONEER study, a prospective, randomised, double-blind, placebo-controlled phase 2b trial comparing inebilizumab with placebo/saline (19 vs 19 participants) in post-acute infection syndromes fulfilling ME/CFS criteria, with a protocol-defined interval of at least six months after immunoadsorption to minimise carry-over effects.