Ca2+-dependent anti-GQ1b antibody in GQ1b-seronegative Fisher syndrome and related disorders

•A study especially focusing on GQ1b-seronegative Fisher syndrome-related disorders•The majority of the seronegative patients had Ca2 +-dependent anti-GQ1b antibodies.•GQ1b-related pathology would be more extensively involved in the disorders.•Ca2 +-dependent anti-GQ1b antibody might specifically recognize GQ1b-Ca2 + complex.•This is the first demonstration of Ca2 +-dependent antibodies in neurological field.

Although serum IgG anti-ganglioside GQ1b antibody is the most specific biomarker for Fisher syndrome and its related disorders (FS-RD), 10%–30% of the patients are still negative in conventional assays (“GQ1b-seronegative”) and the relationship between GQ1b-seropositive and -seronegative patients has been unclear. Some molecules require Ca2+ cations to interact with their ligands (Ca2+-dependency). Here we have investigated whether Ca2+-dependency is also present in anti-GQ1b antibodies in FS-RD, especially in the GQ1b-seronegative patients and show that IgG antibodies against GQ1b-related antigens (isolated GQ1b and GQ1b-containing complexes) are detected Ca2+-dependently in the majority of GQ1b-seronegative patients with FS-RD. The Ca2+-dependent antibodies might react specifically with GQ1b-Ca2+ conformation. This is the first demonstration of disease-related Ca2+-dependent antibodies in neurological field. GQ1b-related pathology would be involved in FS-RD more extensively than previously revealed.

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