Paraneoplastic Anti-Neuronal Nuclear Antibody Type 3 Neurologic Autoimmunity

The amplitudes and velocities of the sensory nerve conduction studies, accompanied by lab-specific normal values Sensory nerve conduction studies Nerve Amplitude (μV) Normal amplitude (μV) Velocity (m/s) Normal velocity (m/s) Median (Digit 3) 2.3 >10 39.9 >48 Ulnar 12.1 >12 38.7 >48 Radial 6.1 >10 46.6 >48 Sural Not recordable >5 Not recordable >40 Superficial fibular Not recordable >5 Not recordable >40 Serum neural antibody testing at the London Health Sciences Centre Clinical Immunology Laboratory detected ANNA-3/Dachshund-homolog 1 (DACH1)–immunoglobulin G (IgG) by mouse tissue indirect immunofluorescence (TIIF) (Fig. 1), which was confirmed by cell-based assay at the Mayo Clinic Neuroimmunology Laboratory. In 2001, Chan et al. identified ANNA-3 in 11 of 68,000 patients with suspected PNS, based on characteristic immunofluorescence staining of mouse tissue sections.1 Zekeridou et al. recently determined the ANNA-3 antigen to be DACH1 and reviewed the available clinical information of 30 ANNA-3/DACH1-IgG-positive patients identified over a 28-year period.3 Among them, 27 (90%) had evidence of malignancy. [...]the treatment for PNS consists of treating the underlying malignancy and immunosuppressive therapies.5 Eight of 11 patients with ANNA-3/DACH1 neurologic autoimmunity had improvement in their PNS with cancer and/or immunosuppressive treatment.3 Two patients with SCLC were treated with ICI, which either exacerbated their ANNA-3 disease or made it appear.3 In other case reports of patients with preexisting PNS, treatment with ICI therapy has been associated with a worsening of neurologic symptoms.6,7,8 Given the limited data, we recommend caution and multidisciplinary management with neuro-oncology expertise if utilization of ICI therapy is being considered in these rare cases.