Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.
Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy ("CAR"-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). Among 16 patients with CRMP-5-IgG and optic neuritis (aged 52-74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR-IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4(+) (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7-32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP-5-IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8(+) T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small-cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity. In summary, CRMP-5-IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer.
Cross
Shelley A
SA
Department of Neurology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Salomao
Diva R
DR
Parisi
Joseph E
JE
Kryzer
Thomas J
TJ
Bradley
Elizabeth A
EA
Mines
Jonathan A
JA
Lam
Byron L
BL
Lennon
Vanda A
VA
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D018288:Carcinoma, Small Cell / Q000150:complications* / Q000276:immunology*; D003937:Diagnosis, Differential; D004596:Electroretinography / Q000379:methods; D005260:Female; D006801:Humans; D006867:Hydrolases; D007074:Immunoglobulin G / Q000276:immunology*; D008175:Lung Neoplasms / Q000150:complications* / Q000276:immunology*; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism; D009471:Neuromyelitis Optica / Q000175:diagnosis; D009900:Optic Nerve / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009902:Optic Neuritis / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D012173:Retinitis / Q000150:complications* / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D007074:Immunoglobulin G; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C415087:DPYSL5 protein, human; D006867:Hydrolases