Anti-amphiphysin antibody positive autoimmune syndrome: case series and literature review

Background and purpose Paraneoplastic neurological syndromes (PNS) is an uncommon disorder affecting the central nervous system (CNS), peripheral nervous system, or autonomic nervous system. The aim of this study was to analyze the clinical characteristics of anti-amphiphysin-IgG-positive autoimmune syndrome and to assess its association with a spectrum of​ anti-amphiphysin-IgG-associated autoimmune syndromes and tumors. Methods We reported clinical data of four patients with anti-amphiphysin-IgG-positive autoimmune syndrome, and conducted a literature review. Result Four amphiphysin-IgG-positive cases were identified. Within our cohort, antibodies feature was comprised of isolated amphiphysin-IgG (2/4), coexisting aquaporin-4-immunoglobulin G (AQP4-IgG) (1/4), coexisting N-methyl- D -aspartate receptor immunoglobulin G (NMDAR-IgG) (1/4). Clinical presentation included conus medullaris-cauda equina syndrome (1/4), myelitis (2/4) and stiff-person syndrome (SPS) (1/4). The coexisting cancer was involved of lung cancer (1/4). Conclusion Anti-amphiphysin-IgG-positive autoimmune syndrome demonstrate heterogeneous clinical presentations, including myelitis, SPS, and rare variants like conus medullaris-cauda equina syndrome. Coexistence with other neural antibodies (e.g., AQP4-IgG or NMDAR-IgG) may elevate tumor risk. While strongly associated with malignancies such as breast and small cell lung cancer (SCLC), combined immunotherapy and oncologic therapy can stabilize or improve neurological function in subsets of patients. Early serologic testing and sustained cancer surveillance are imperative for prompt intervention and prognostic optimization.