Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus

Author:

Krustev EugeneORCID,Hanly John GORCID,Chin Ricky,Buhler Katherine A,Urowitz Murray BORCID,Gordon Caroline,Bae Sang-CheolORCID,Romero-Diaz Juanita,Sánchez-Guerrero Jorge,Bernatsky SashaORCID,Wallace Daniel JORCID,Isenberg David,Rahman AnisurORCID,Merrill Joan T,Fortin Paul RORCID,Gladman Dafna D,Bruce Ian NORCID,Petri Michelle AORCID,Ginzler Ellen MORCID,Dooley Mary Anne,Ramsey-Goldman Rosalind,Manzi SusanORCID,Jönsen Andreas,Alarcón Graciela S,van Vollenhoven Ronald FORCID,Aranow CynthiaORCID,Mackay Meggan,Ruiz-Irastorza GuillermoORCID,Lim SamORCID,Inanc Murat,Kalunian Kenneth C,Jacobsen Søren,Peschken Christine A,Kamen Diane LORCID,Askenase Anca,Buyon Jill,Fritzler Marvin J,Clarke Ann E,Choi May YORCID

Abstract

BackgroundCranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort.MethodsIndividuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up.ResultsOf the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1).ConclusionAnti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Funder

National Institute for Health Research Manchester Biomedical Research Centre

Gigtforeningen

LUPUS UK

Canadian Institutes of Health Research

Department of Education, Universities and Research of the Basque Government

Canada Research Chairs

The Arthritis Society

Novo Nordisk Fonden

Mitogen Dx

Singer Family Foundation

National Institute for Health Research University College London Hospitals Biomedical Research Centre

Lupus Foundation of America

Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education

National Institutes of Health

NIHR/Wellcome Trust Clinical Research Facility Birmingham

Sandwell and West Birmingham Hospitals NHS Trust

Publisher

BMJ

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