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102 M-Phase Phosphoprotein 1 (MPP-1) Autoantibodies as a Potential Biomarker for Cranial Neuropathies in an International SLE Inception Cohort
  1. Eugene Krustev1,
  2. John G Hanly2,
  3. Ricky Chin1,
  4. Katherine Buhler1,
  5. Francesca Cardwell3,
  6. Murray B Urowitz4,
  7. Caroline Gordon5,
  8. Sang-Cheol Bae6,
  9. Juanita Romero-Diaz7,
  10. Jorge Sanchez-Guerrero8,
  11. Sasha Bernatsky9,
  12. Daniel J Wallace10,
  13. David A Isenberg11,
  14. Anisur Rahman11,
  15. Joan T Merrill12,
  16. Paul R Fortin13,
  17. Dafna D Gladman2,
  18. Ian N Bruce14,
  19. Michelle Petri15,
  20. Ellen M Ginzler16,
  21. Mary Anne Dooley17,
  22. Rosalind Ramsey-Goldman18,
  23. Susan Manzi19,
  24. Andreas Jönsen20,
  25. Graciela S Alarcón21,
  26. Ronald F van Vollenhoven22,
  27. Cynthia Aranow23,
  28. Meggan Mackay23,
  29. Guillermo Ruiz-Irastorza24,
  30. Sam Lim25,
  31. Murat Inanc26,
  32. Kenneth C Kalunian27,
  33. Søren Jacobsen28,
  34. Christine A Peschken29,
  35. Diane L Kamen30,
  36. Anca Askanase31,
  37. Jill Buyon32,
  38. Marvin J Fritzler1,
  39. Ann E Clarke1 and
  40. May Y Choi1
  1. 1University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
  2. 2Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  3. 3University of Waterloo, Burlington, ON, Canada
  4. 4Lupus Program, Centre for Prognosis Studies in The Rheumatic Disease and Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
  5. 4Research Institute of the McGill University Health Centre; Montreal, Quebec, Canada
  6. 5Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  7. 6Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology, Seoul, Korea
  8. 7Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico
  9. 8Mount Sinai Hospital and University Health Network, University of Toronto, Canada
  10. 9Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre
  11. 10Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, California, USA
  12. 11Centre for Rheumatology, Department of Medicine, University College London, UK
  13. 12Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  14. 13Division of Rheumatology, CHU de Québec – Université Laval, Québec City, Canada
  15. 14NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, Greater Manchester, UK and Centre for Epidemiology Versus Arthritis, Faculty of Biology, Medicine and Health, The University of Manchester, UK
  16. 15Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  17. 16Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
  18. 17Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
  19. 18Northwestern University and Feinberg School of Medicine, Chicago, Illinois, USA
  20. 19Allegheny Health Network, Pittsburgh, Pennsylvania, USA
  21. 20Lund University, Lund, Sweden
  22. 21Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  23. 22University of Amsterdam, Rheumatology and Immunology Center, Amsterdam, Noord-Holland, The Netherlands
  24. 23Feinstein Institute for Medical Research, Manhasset, New York, USA
  25. 24Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain
  26. 25Emory University School of Medicine, Division of Rheumatology, Atlanta, Georgia, USA
  27. 26Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
  28. 27University of California San Diego School of Medicine, La Jolla, California, USA
  29. 28Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  30. 29University of Manitoba, Winnipeg, Manitoba, Canada
  31. 30Medical University of South Carolina, Charleston, South Carolina, USA
  32. 31Hospital for Joint Diseases, New York University, Seligman Centre for Advanced Therapeutics, New York New York, USA
  33. 32New York University School of Medicine, New York, NY


Objectives We previously reported in a single centre prevalent SLE cohort that antibodies against the cytokinesis-associated protein M-Phase Phosphoprotein 1 (anti-MPP-1) were associated with SLE-related cranial neuropathy (CN), a rare manifestation of neuropsychiatric SLE (NPSLE). The purpose of this study was to assess whether anti-MPP-1 is a biomarker for CN or other NPSLE manifestations using an international SLE inception cohort.

Methods SLE patients fulfilling the updated 1997 ACR classification criteria for SLE were included. Anti-MPP-1 antibody testing was performed on baseline samples (within 15 months of diagnosis) or first annual assessment using an addressable laser bead immunoassay (ALBIA) with purified recombinant human protein with results expressed as median florescence units (MFU). Based on healthy controls, a dilution of ≥1:500 MFU was considered positive. NPSLE manifestations occurring over the first 5 years of follow up were documented annually based on ACR case definitions using published NPSLE attribution rules1). The frequency of anti-MPP- 1 positivity between patients with versus without each of the 19 NPSLE manifestations was compared using univariate logistic regression. For any NPSLE manifestations where anti-MPP-1 positivity differed between patients with versus without the manifestation, baseline demographic and clinical characteristics were compared using t-tests and two-sample tests of proportions. For NPSLE manifestations associated with anti-MPP-1 positivity in the univariate analysis, multivariable logistic regression analysis using penalized maximum likelihood estimates was then performed to assess the relationship between anti-MPP-1 and the NPSLE manifestation, adjusting for age at anti-MPP-1 testing, female, White race/ethnicity, and significantly different baseline clinical characteristics.

Results Seven hundred and ninety-five SLE patients were assessed; 29.8% were anti-MPP-1 positive, 88.7% female, and 52.1% White. The frequency of anti-MPP-1 positivity differed only for those with versus without CN (70.0% vs. 29.3%; odds ratio [OR] 5.16, 95%CI 1.44, 18.54) (table 1).

Compared to patients without CN (n=785), patients with CN (n=10) were more likely to fulfill the ACR hematologic (difference: 23.9%, 95%CI 5.0%, 42.8%) and antinuclear antibody criteria (difference: 4.3%, 95%CI 2.9%, 5.8%) (table 2). In the multivariate analysis, anti-MPP-1 remained associated with CN (OR 5.24, 95%CI 1.44, 19.09) after adjusting for age at anti-MPP-1 testing, female, White race/ethnicity, hematologic disorder, and antinuclear antibody (table 3).

Conclusion Anti-MPP-1 is a potential biomarker for CN. Although anti-MPP-1 is differentially expressed in a variety of neurological cells and tissues, the link to a pathogenic role requires further study.


  1. Hanly, J. G., Urowitz, M. B., Gordon, C., et al. Ann Rheum Dis. 2020; 79(3): 356–362.

  2. Ainiala H , Hietaharju A , Loukkola J , et al . Arthritis Rheum 2001 ;45: 419–23.

Abstract 102 Table 1

Distribution of MPP-1 positivity at baseline between patients with versus without NPSLE manifestations* within 5 years of follow-up

Abstract 102 Table 2

Comparison of baseline demographic and clinical characteristics of SLE patients with versus without cranial neuropathy within 5 years of follow-up

Abstract 102 Table 3

Multivariate analysis examining the association between MPP-1 positivity and cranial neuropathy within 5 years of follow-up

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