Clinical Significance of Kelch-like Protein 11 Antibodies (4294)

Objective: To report the clinical and oncological associations of antibodies against Kelch-like 11 protein (KLHL11-abs) and to analyze the value of routine immunohistochemistry in the screening of these antibodies. Background: KLHL11-abs have been recently proposed as a new biomarker of paraneoplastic brainstem/cerebellar syndrome and testicular seminoma. However, the spectrum of neurological syndromes and tumors related to these antibodies is unknown. Design/Methods: KLHL11-abs were determined using a cell-based assay (CBA) with HEK293T cells transfected with a human KLHL11 clone and immunoprecipitation. Positive samples were assessed by immunohistochemistry on rat brain sections. Overall, we examined sera of 420 patients with the following disorders: 157 paraneoplastic syndromes, 172 autoimmune neurological disorders, 63 neurological symptoms in the setting of teratomas, 28 isolated small-cell lung cancer (SCLC), and 12 healthy subjects. Results: KLHL11-abs were detected in 32 patients by CBA (all confirmed by immunoprecipitation). Immunohistochemistry on rat brain only detected 7 (21%) of the KLHL11-ab-positive samples. Patients’ median age was 28.5 years (range 9 – 76), 16 (50%) were women. Fourteen (44%) patients had benign teratomas (10 ovarian, 4 testicular) and 7 (22%) testicular or thymic seminomas or mixed germ-cell tumors, 1 ovarian carcinoma and 1 SCLC. Neurological syndromes included: 7 (22%) cases with cerebellar ataxia, 6 (19%) widespread encephalitis with predominant involvement of brainstem and cerebellum, 7 (22%) anti-NMDAR encephalitis (5 with ovarian teratoma), 5 (16%) opsoclonus-myoclonus, 3 (9%) limbic encephalitis, and 4 (12%) diverse neurological symptoms (3 associated with teratomas). Thirteen (41%) patients had concomitant antibodies (7 anti-NMDAR, and 6 onconeuronal). Conclusions: KLHL11-abs associate with a much broader spectrum of neurological syndromes and tumors than previously reported. They may also occur in well-defined autoimmune encephalitis (anti-NMDAR encephalitis or Ma2 encephalitis) without clinically modifying their phenotype. Routine rat brain immunohistochemistry is not useful for the screening of these antibodies. Disclosure: Dr. Landa has nothing to disclose. Dr. Maudes has nothing to disclose. Dr. Munoz has nothing to disclose. Dr. Armangue has received research support from Mutua Madrilena Foundation. Dr. Saiz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received remuneration for providing consulting services and lectures from Bayer, Merck-Serono, Biogen, Sanofi, Teva, Roche and Novartis. Dr. Graus has nothing to disclose. Dr. Dalmau has received personal compensation in an editorial capacity for Editor: Neurology, Neuroimmunology, Neuroinflammation; and UpToDate. Dr. Dalmau has received royalty, license fees, or contractual rights payments from Euroimmune. Dr. Dalmau has received research support from Sage therapeutics. Dr. Sabater has nothing to disclose.