M-Phase Phosphoprotein 1 (MPP-1) Autoantibodies as a Potential Biomarker for Cranial Neuropathies in an International SLE Inception Cohort

Eugene Krustev¹, John Hanly², Ricky Chin³, Katherine Buhler¹, Francesca S Cardwell⁴, Murray Urowitz⁵, Caroline Gordon⁶, Sang-Cheol Bae⁷, Juanita Romero-Diaz⁸, Jorge Sanchez-Guerrero⁹, Sasha Bernatsky¹⁰, Daniel Wallace¹¹, David Isenberg¹², Anisur Rahman¹³, Joan Merrill¹⁴, Paul R Fortin¹⁵, Dafna Gladman¹⁶, Ian N. Bruce¹⁷, Michelle Petri¹⁸, Ellen M. Ginzler¹⁹, Mary Anne Dooley²⁰, Rosalind Ramsey-Goldman²¹, Susan Manzi²², Andreas Jönsen²³, Graciela Alarcón²⁴, Ronald van Vollenhoven²⁵, Cynthia Aranow²⁶, Meggan Mackay²⁶, Guillermo Ruiz-Irastorza²⁷, S. Sam Lim²⁸, Murat İnanç²⁹, Kenneth Kalunian³⁰, Soren Jacobsen³¹, Christine Peschken³², Diane Kamen³³, Anca Askanase³⁴, Jill Buyon³⁵, Marvin Fritzler¹, Ann E Clarke³⁶ and May Choi³⁷, ¹University of Calgary, Calgary, AB, Canada, ²Division of Rheumatology, Queen Elizabeth II Health Sciences Center (Nova Scotia Rehabilitation Site) and Dalhousie University, Halifax, NS, Canada, ³University of Calgary, Ottawa, ON, Canada, ⁴University of Waterloo, Department of Geography & Environmental Management, Burlington, ON, Canada, ⁵University of Toronto, University Health Network, Schroeder Arthritis Institute, Toronto, ON, Canada, ⁶Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom, ⁷Hanyang University Medical Center, Seoul, Republic of Korea, ⁸Instituto Nacional de Ciencias Medicas y Nutricion SZ, Ciudad de México, Mexico, ⁹Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, ON, Canada, ¹⁰Research Institute of the McGill University Health Centre, Montréal, QC, Canada, ¹¹Cedars-Sinai Medical Center, Los Angeles, CA, ¹²University College London, London, United Kingdom, ¹³Centre for Rheumatology, Department of Medicine, University College London, London, United Kingdom, ¹⁴Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹⁵Centre ARThrite - CHU de Québec - Université Laval, Québec, QC, Canada, ¹⁶Toronto Western Hospital, Schroeder Arthritis Institute, Toronto, ON, Canada, ¹⁷Centre for Epidemiology Versus Arthritis, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom, ¹⁸Johns Hopkins University School of Medicine, Division of Rheumatology, Baltimore, MD, ¹⁹SUNY Downstate Health Sciences University, Department of Medicine, Brooklyn, NY, ²⁰Raleigh Neurology Associates, Chapel Hill, NC, ²¹Northwestern University Feinberg School of Medicine, Chicago, USA, Chicago, IL, ²²Allegheny Health Network, Lupus Center of Excellence, Wexford, PA, ²³Department of Clinical Sciences, Lund, Section for Rheumatology, Lund University, Lund and Skåne University Hospital, Lund, Sweden, ²⁴The University of Alabama at Birmingham, Oakland, ²⁵Amsterdam University Medical Centers, Amsterdam, Netherlands, ²⁶Feinstein Institutes for Medical Research, Manhasset, NY, ²⁷Autoimmune Diseases Research Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, UPV/EHU, Barakaldo, Spain, ²⁸Emory University, Atlanta, GA, ²⁹Istanbul University Faculty of Medicine, Istanbul, Turkey, ³⁰University of California San Diego, La Jolla, CA, ³¹Rigshospitalet, Copenhagen, Denmark, ³²University of Manitoba, Winnipeg, MB, Canada, ³³Medical University of South Carolina, Charleston, SC, ³⁴Columbia University Medical Center, New York, NY, ³⁵NYU Grossman School of Medicine, New York, NY, ³⁶University of Calgary, Division of Rheumatology, Cumming School of Medicine, Calgary, AB, Canada, ³⁷Brigham and Women's Hospital | University of Calgary, Calgary, AB, Canada

Meeting: ACR Convergence 2022

Keywords: Autoantibody(ies), Biomarkers, neuropsychiatric disorders, Systemic lupus erythematosus (SLE)

Session Information

Date: Saturday, November 12, 2022

Title: SLE – Diagnosis, Manifestations, and Outcomes Poster I: Diagnosis

Session Type: Poster Session A

Session Time: 1:00PM-3:00PM

Background/Purpose: 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 rules [1]). 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 with complete data for 5 years of follow up were assessed; 29.8% were anti-MPP1 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-MPP1 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 in SLE. Although anti-MPP-1 is differentially expressed in a variety of neurological cells and tissues, the link to a pathogenic role requires further study.

References:
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.

Disclosures: E. Krustev, Intercept Pharmaceuticals Inc, Mountain Valley MD Holdings INC, Gilead Sciences INC; J. Hanly, None; R. Chin, None; K. Buhler, None; F. Cardwell, None; M. Urowitz, None; C. Gordon, UCB, Amgen, Astra-Zeneca, AbbVie, Sanofi, MGP; S. Bae, None; J. Romero-Diaz, Biogen; J. Sanchez-Guerrero, None; S. Bernatsky, None; D. Wallace, None; D. Isenberg, Merck/MSD, astra zeneca, Eli Lilly, Servier, Amgen; A. Rahman, None; J. Merrill, UCB, GlaxoSmithKline, AbbVie, EMD Serono, Remegen, Celgene/Bristol Myers Squibb, AstraZeneca, Amgen, Janssen, Lilly, Genentech, Aurinia, Astellas, Alexion, Sanofi, Zenas, Proventio; P. Fortin, AstraZeneca, GlaxoSmithKlein(GSK); D. Gladman, AbbVie, Amgen, Eli Lilly, Janssen, Gilead, Novartis, Pfizer, Bristol-Myers Squibb(BMS), Galapagos, UCB Pharma, Celgene; I. Bruce, AstraZeneca, Bristol-Myers Squibb(BMS), Eli Lilly, Aurinia, Janssen, GlaxoSmithKlein(GSK); M. Petri, Exagen, AstraZeneca, Alexion, Amgen, AnaptysBio, Argenx, Aurinia, Biogen, Caribou Biosciences, CVS Health, EMD Serono, Eli Lilly, Emergent Biosolutions, GlaxoSmithKline (GSK), IQVIA, Janssen, Kira Pharmaceuticals, MedShr, Sanofi, SinoMab, Thermofisher, BPR Scientific Advisory Committee; E. Ginzler, Aurinia Pharma; M. Dooley, None; R. Ramsey-Goldman, None; S. Manzi, AstraZeneca, GlaxoSmithKline (GSK), Exagen Diagnostics Inc, AbbVie, HGS, Cugene, Lilly, UCB Advisory Board, Lupus Foundation of America; A. Jönsen, None; G. Alarcón, None; R. van Vollenhoven, Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK), UCB, Merck/MSD, Pfizer, Roche, AbbVie, AstraZeneca, Biogen, Galapagos, Janssen, Miltenyi, R-Pharma; C. Aranow, None; M. Mackay, None; G. Ruiz-Irastorza, None; S. Lim, None; M. İnanç, None; K. Kalunian, AbbVie/Abbott, Amgen, AstraZeneca, Aurinia, Biogen, Bristol Myers Squibb (BMS), Eli Lilly, Equillium, Genentech, Gilead, Janssen, Roche, Lupus Research Alliance, Pfizer, Sanford Consortium, Viela, Nektar; S. Jacobsen, None; C. Peschken, None; D. Kamen, None; A. Askanase, AstraZeneca, GlaxoSmithKlein(GSK), Aurinia, Amgen, Pfizer, Idorsia, Eli Lilly, UCB, AbbVie/Abbott, Janssen, Bristol-Myers Squibb(BMS); J. Buyon, None; M. Fritzler, Mitogen Diagnostics Corporation; A. Clarke, AstraZeneca, Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK); M. Choi, AstraZeneca, MitogenDx, mallinckrodt, Janssen, AbbVie/Abbott, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol-Myers Squibb(BMS), Celltrion, Ferring, Fresenius Kabi, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche.

To cite this abstract in AMA style:

Krustev E, Hanly J, Chin R, Buhler K, Cardwell F, Urowitz M, Gordon C, Bae S, Romero-Diaz J, Sanchez-Guerrero J, Bernatsky S, Wallace D, Isenberg D, Rahman A, Merrill J, Fortin P, Gladman D, Bruce I, Petri M, Ginzler E, Dooley M, Ramsey-Goldman R, Manzi S, Jönsen A, Alarcón G, van Vollenhoven R, Aranow C, Mackay M, Ruiz-Irastorza G, Lim S, İnanç M, Kalunian K, Jacobsen S, Peschken C, Kamen D, Askanase A, Buyon J, Fritzler M, Clarke A, Choi M. M-Phase Phosphoprotein 1 (MPP-1) Autoantibodies as a Potential Biomarker for Cranial Neuropathies in an International SLE Inception Cohort [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/m-phase-phosphoprotein-1-mpp-1-autoantibodies-as-a-potential-biomarker-for-cranial-neuropathies-in-an-international-sle-inception-cohort/. Accessed .

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