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

Eugene Krustev; John G Hanly; Ricky Chin; Katherine A Buhler; Murray B Urowitz; Caroline Gordon; Sang-Cheol Bae; Juanita Romera-Diaz; Jorge Sanchez-Guerrero; Sasha Bernatsky; Daniel J Wallace; David Isenberg; Anisur Rahman; Joan T Merrill; Paul R Fortin; Dafna D Gladman; Ian N Bruce; Michelle A Petri; Ellen M Ginzler; Mary Anne Dooley; Rosalind Ramsey-Goldman; Susan Manzi; Andreas Jönsen; Graciela S Alarcón; Ronald F van Vollenhoven; Cynthia Aranow; Meggan Mackay; Guillermo Ruiz-Irastorza; Sam Lim; Murat Inanc; Kenneth C Kalunian; Søren Jacobsen; Christine A Peschken; Diane L Kamen; Anca Askenase; Jill Buyon; Marvin J Fritzler; Ann E Clarke; May Y Choi

doi:10.1136/lupus-2023-001139

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

Eugene Krustev, John G Hanly, Ricky Chin, Katherine A Buhler, Murray B Urowitz, Caroline Gordon, Sang-Cheol Bae, Juanita Romera-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Daniel J Wallace, David Isenberg, Anisur Rahman, Joan T Merrill, Paul R Fortin, Dafna D Gladman, Ian N Bruce, Michelle A Petri, Ellen M Ginzler, Mary Anne DooleyRosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S Alarcón, Ronald F van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Kenneth C Kalunian, Søren Jacobsen, Christine A Peschken, Diane L Kamen, Anca Askenase, Jill Buyon, Marvin J Fritzler, Ann E Clarke, May Y Choi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Cranial 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.

Methods: Individuals 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.

Results: Of 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).

Conclusion: Anti-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.

Original language	English
Article number	e001139
Number of pages	9
Journal	Lupus Science and Medicine
Volume	11
Issue number	1
DOIs	https://doi.org/10.1136/lupus-2023-001139
Publication status	Published - 9 Apr 2024

Bibliographical note

Funding:
The cost of the immunoassay supplies and labour was supported by the Lupus Foundation of America and MitogenDx. MYC is supported by the Lupus Foundation of America Gary S Gilkeson Career Development Award and research gifts in kind from MitogenDx (Calgary, Canada). AEC holds the Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary. JGH’s work was supported by the Canadian Institutes of Health Research (research grant MOP-88526). CG’s work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the NIHR/Wellcome Trust Clinical Research Facility in Birmingham. S-CB is supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899). The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. AR and DI are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The Hopkins Lupus Cohort is supported by NIH Grants AR043727 and AR069572. PRF presently holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval and part of this work was done while he was still holding a Distinguished Senior Investigator position at the Arthritis Society. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre (NIHR203308). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. MAD’s work was supported by NIH Grant RR00046. RR-G’s work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098). SM is supported by Grants R01 AR046588 and K24 AR002213. GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990).

Keywords

Autoimmune Diseases
Systemic Lupus Erythematosus
Antibodies
Autoantibodies

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Krustev, E., Hanly, J. G., Chin, R., Buhler, K. A., Urowitz, M. B., Gordon, C., Bae, S.-C., Romera-Diaz, J., Sanchez-Guerrero, J., Bernatsky, S., Wallace, D. J., Isenberg, D., Rahman, A., Merrill, J. T., Fortin, P. R., Gladman, D. D., Bruce, I. N., Petri, M. A., Ginzler, E. M., ... Choi, M. Y. (2024). Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus. Lupus Science and Medicine, 11(1), Article e001139. https://doi.org/10.1136/lupus-2023-001139

@article{5214244edca743afbf9c57a3c5acc44a,

title = "Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus",

abstract = "Background: Cranial 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. Methods: Individuals 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. Results: Of 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). Conclusion: Anti-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.",

keywords = "Autoimmune Diseases, Systemic Lupus Erythematosus, Antibodies, Autoantibodies",

author = "Eugene Krustev and Hanly, {John G} and Ricky Chin and Buhler, {Katherine A} and Urowitz, {Murray B} and Caroline Gordon and Sang-Cheol Bae and Juanita Romera-Diaz and Jorge Sanchez-Guerrero and Sasha Bernatsky and Wallace, {Daniel J} and David Isenberg and Anisur Rahman and Merrill, {Joan T} and Fortin, {Paul R} and Gladman, {Dafna D} and Bruce, {Ian N} and Petri, {Michelle A} and Ginzler, {Ellen M} and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas J{\"o}nsen and Alarc{\'o}n, {Graciela S} and {van Vollenhoven}, {Ronald F} and Cynthia Aranow and Meggan Mackay and Guillermo Ruiz-Irastorza and Sam Lim and Murat Inanc and Kalunian, {Kenneth C} and S{\o}ren Jacobsen and Peschken, {Christine A} and Kamen, {Diane L} and Anca Askenase and Jill Buyon and Fritzler, {Marvin J} and Clarke, {Ann E} and Choi, {May Y}",

note = "Funding: The cost of the immunoassay supplies and labour was supported by the Lupus Foundation of America and MitogenDx. MYC is supported by the Lupus Foundation of America Gary S Gilkeson Career Development Award and research gifts in kind from MitogenDx (Calgary, Canada). AEC holds the Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary. JGH{\textquoteright}s work was supported by the Canadian Institutes of Health Research (research grant MOP-88526). CG{\textquoteright}s work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the NIHR/Wellcome Trust Clinical Research Facility in Birmingham. S-CB is supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899). The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. AR and DI are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The Hopkins Lupus Cohort is supported by NIH Grants AR043727 and AR069572. PRF presently holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Universit{\'e} Laval and part of this work was done while he was still holding a Distinguished Senior Investigator position at the Arthritis Society. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre (NIHR203308). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. MAD{\textquoteright}s work was supported by NIH Grant RR00046. RR-G{\textquoteright}s work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098). SM is supported by Grants R01 AR046588 and K24 AR002213. GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990).",

year = "2024",

month = apr,

day = "9",

doi = "10.1136/lupus-2023-001139",

language = "English",

volume = "11",

journal = "Lupus Science and Medicine",

issn = "2053-8790",

publisher = "BMJ Publishing Group",

number = "1",

}

Krustev, E, Hanly, JG, Chin, R, Buhler, KA, Urowitz, MB, Gordon, C, Bae, S-C, Romera-Diaz, J, Sanchez-Guerrero, J, Bernatsky, S, Wallace, DJ, Isenberg, D, Rahman, A, Merrill, JT, Fortin, PR, Gladman, DD, Bruce, IN, Petri, MA, Ginzler, EM, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jönsen, A, Alarcón, GS, van Vollenhoven, RF, Aranow, C, Mackay, M, Ruiz-Irastorza, G, Lim, S, Inanc, M, Kalunian, KC, Jacobsen, S, Peschken, CA, Kamen, DL, Askenase, A, Buyon, J, Fritzler, MJ, Clarke, AE & Choi, MY 2024, 'Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus', Lupus Science and Medicine, vol. 11, no. 1, e001139. https://doi.org/10.1136/lupus-2023-001139

TY - JOUR

T1 - Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus

AU - Krustev, Eugene

AU - Hanly, John G

AU - Chin, Ricky

AU - Buhler, Katherine A

AU - Urowitz, Murray B

AU - Gordon, Caroline

AU - Bae, Sang-Cheol

AU - Romera-Diaz, Juanita

AU - Sanchez-Guerrero, Jorge

AU - Bernatsky, Sasha

AU - Wallace, Daniel J

AU - Isenberg, David

AU - Rahman, Anisur

AU - Merrill, Joan T

AU - Fortin, Paul R

AU - Gladman, Dafna D

AU - Bruce, Ian N

AU - Petri, Michelle A

AU - Ginzler, Ellen M

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jönsen, Andreas

AU - Alarcón, Graciela S

AU - van Vollenhoven, Ronald F

AU - Aranow, Cynthia

AU - Mackay, Meggan

AU - Ruiz-Irastorza, Guillermo

AU - Lim, Sam

AU - Inanc, Murat

AU - Kalunian, Kenneth C

AU - Jacobsen, Søren

AU - Peschken, Christine A

AU - Kamen, Diane L

AU - Askenase, Anca

AU - Buyon, Jill

AU - Fritzler, Marvin J

AU - Clarke, Ann E

AU - Choi, May Y

N1 - Funding: The cost of the immunoassay supplies and labour was supported by the Lupus Foundation of America and MitogenDx. MYC is supported by the Lupus Foundation of America Gary S Gilkeson Career Development Award and research gifts in kind from MitogenDx (Calgary, Canada). AEC holds the Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary. JGH’s work was supported by the Canadian Institutes of Health Research (research grant MOP-88526). CG’s work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the NIHR/Wellcome Trust Clinical Research Facility in Birmingham. S-CB is supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899). The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research. AR and DI are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The Hopkins Lupus Cohort is supported by NIH Grants AR043727 and AR069572. PRF presently holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval and part of this work was done while he was still holding a Distinguished Senior Investigator position at the Arthritis Society. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre (NIHR203308). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. MAD’s work was supported by NIH Grant RR00046. RR-G’s work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098). SM is supported by Grants R01 AR046588 and K24 AR002213. GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990).

PY - 2024/4/9

Y1 - 2024/4/9

N2 - Background: Cranial 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. Methods: Individuals 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. Results: Of 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). Conclusion: Anti-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.

AB - Background: Cranial 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. Methods: Individuals 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. Results: Of 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). Conclusion: Anti-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.

KW - Autoimmune Diseases

KW - Systemic Lupus Erythematosus

KW - Antibodies

KW - Autoantibodies

U2 - 10.1136/lupus-2023-001139

DO - 10.1136/lupus-2023-001139

M3 - Article

SN - 2053-8790

VL - 11

JO - Lupus Science and Medicine

JF - Lupus Science and Medicine

IS - 1

M1 - e001139

ER -

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

Abstract

Bibliographical note

Keywords

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