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Stop testing for autoantibodies to the VGKC-complex: only request LGI1 and CASPR2
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  • Published on: 23 May 2024
    Two wrongs don’t make a right: the multiple pitfalls of being double negative
    • Sarosh Irani, Neurologist Mayo Clinic, Jacksonville Florida
    • Other Contributors:
      • John Soltys, Neurologist
      • Anna Harrison, Neurologist

    Dear Editor,
    In conversations and correspondences with colleagues, we are often still asked if our pre-pandemic call to “stop testing for VGKC antibodies” (1, 2), as echoed by others (3-5), has stood the test of time. Recent articles have raised public health and patient safety concerns, particularly around neurology temporally associated with COVID infections, prompting us to continue to strongly advocate for this stance and avoid misinterpreting positive neurologic antibody results (6-15).
    Indeed, the misinterpretation of double negative VGKC-antibodies (dnVGKC; samples with VGKC-complex immunoprecipitation but no LGI1 or CASPR2 reactivity) remains a leading cause of AE misdiagnosis, a problem which now appears to overwhelm the rates of accurate AE diagnosis (16, 17). Patients given this misdiagnosis often experience adverse effects from immunotherapies, and suffer from a misdirected clinical journey (14) given most harbour an alternative, non-immunological underlying diagnosis.
    An important explanation has been independently demonstrated in large-cohort studies: dnVGKC antibodies have a high false positive rate at approximately five percent in healthy and other neurological disorder control populations (1, 4). This rate is likely a conservative estimate, as many labs utilize a more liberal cut-off, further exacerbating the irrelevance of dnVGKC antibodies (18). If interpreted as a surrogate of disease incidence, one could conservatively diagnose AE in...

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    Conflict of Interest:
    None declared.

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