Clinical significance of Kelch-like protein 11 antibodies.

Abstract

OBJECTIVE:

To report the clinical and oncologic associations of antibodies against Kelch-like protein 11 (KLHL11-ab), recently suggested as biomarkers of a paraneoplastic brainstem cerebellar syndrome associated with testicular seminoma, and to determine the value of immunohistochemistry as a screening technique.

METHODS:

Studies included 432 sera or CSF from 329 patients with paraneoplastic (157) or autoimmune neurologic syndromes (172); 63 with neurologic symptoms and benign teratomas; 28 with small-cell lung cancer, and 12 healthy subjects. KLHL11-abs were examined using a cell-based assay (CBA) with HEK293 cells transfected with a human KLHL11 clone. The CBA specificity was confirmed by immunoprecipitation. All positive samples were examined by immunohistochemistry on rat brain sections.

RESULTS:

KLHL11-abs were detected in 32 patients by CBA, and patients' antibodies immunoprecipitated KLHL11. Using rat brain immunohistochemistry, only 7 samples (22%) were positive. Patients' median age was 28 years (range 9-76 years), and 16 (50%) were women. Tumors were identified in 23/32 (72%) patients, including 14 teratomas and 7 seminomas or mixed germ cell tumors. Thirteen (41%) patients had cerebellar ataxia (7) or encephalitis with brainstem cerebellar symptoms (6), 7 (22%) anti-NMDA receptor (NMDAR) encephalitis (5 with ovarian teratoma), 5 (16%) opsoclonus-myoclonus, 3 (9%) limbic encephalitis, and 4 (12%) diverse neurologic symptoms (3 with benign teratomas). Concurrent autoantibodies occurred in 14 (44%) patients (7 anti-NMDAR, 6 Ma2, and 1 Hu).

CONCLUSIONS:

KLHL11-abs associate with a spectrum of syndromes and tumors wider than those previously reported; 44% of patients have concurrent neuronal antibodies, some of them (anti-NMDAR) pathogenically relevant. Brain immunostaining is not useful for routine screening of KLHL11-abs.

• Authors: Estibaliz Maudes, Jon Landa, Amaia Muñoz-Lopetegi, Thaís Armangue, Mercedes Alba, Albert Saiz, Francesc Graus, Josep Dalmau, Lidia Sabater
• Journal: Neurology(R) neuroimmunology & neuroinflammation (Neurol Neuroimmunol Neuroinflamm) Vol. 7 Issue 3 (05 2020) ISSN: 2332-7812 [Electronic] United States
• PMID: 31953318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• Autoantibodies
• Carrier Proteins
• KLHL11 protein, human

Topics

• Adolescent
• Adult
• Aged
• Animals
• Autoantibodies (blood, cerebrospinal fluid, immunology)
• Autoimmune Diseases of the Nervous System (blood, cerebrospinal fluid, immunology)
• Carrier Proteins (immunology)
• Child
• Female
• HEK293 Cells
• Humans
• Male
• Middle Aged
• Neoplasms (blood, cerebrospinal fluid, immunology)
• Paraneoplastic Syndromes, Nervous System (blood, cerebrospinal fluid, immunology)
• Rats
• Retrospective Studies
• Young Adult