The double-edged sword: a contemporary perspective on biologics for anti-cytokine syndromes

Introduction Anti-cytokine autoantibodies (ACA) modulate human immunity and may manifest as phenocopies of inborn errors of immunity. Patients typically present with severe, persistent, unusual, or recurrent infections and possible autoimmune manifestations. While prolonged antimicrobials are the traditional standard of care, they frequently lead to drug resistance and adverse effects, highlighting an urgent need for disease-modifying therapies. However, the use of immunosuppressive agents in treating immunodeficiency is a dilemma in the field.Areas covered This review synthesizes current clinical evidence on managing ACA syndromes, with specific focus on interferon-γ, granulocyte-macrophage colony stimulating factor, IL-12/23, IL-6, type 1 IFNs, and IL-10. We evaluate the efficacy and therapeutic rationale of various treatments, including B-cell depletion, plasma exchange, and cytokine replacement, while highlighting the distinct clinical phenotypes and diagnostic strategies for each syndrome.Expert opinion The use of biologics in ACA marks a shift from reactive antimicrobial treatments to proactive targeted immune reconstitution. Clinical use is still restricted by the inherent risks of immunosuppressing actively infected patients and the absence of standardized functional assays for monitoring. Overcoming these barriers will require accessible ACA screening and the development of customized therapies, such as chimeric autoantibody receptor-T, to deliver functional cures and improve long-term patient care.