Abstract
102 M-Phase Phosphoprotein 1 (MPP-1) Autoantibodies as a Potential Biomarker for Cranial Neuropathies in an International SLE Inception Cohort
Lupus science & medicine, v 9(Suppl 3), pp A2-A3
14 Dec 2022
Abstract
ObjectivesWe 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.MethodsSLE 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.ResultsSeven 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).ConclusionAnti-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.ReferencesHanly, J. G., Urowitz, M. B., Gordon, C., et al. Ann Rheum Dis. 2020; 79(3): 356–362.Ainiala H , Hietaharju A , Loukkola J , et al . Arthritis Rheum 2001 ;45: 419–23.Abstract 102 Table 1Distribution of MPP-1 positivity at baseline between patients with versus without NPSLE manifestations* within 5 years of follow-up Any NPSLE manifestation (n=153) No NPSLE manifestation (n=642) Odds Ratio (95%CI) MPP-1 Positive, n,% 42, 27.5% 195, 30.4% 0.87 (0.59-1.28) Any CNS manifestation (n=127) No CNS manifestation (n=668) Odds Ratio (95%CI) MPP-1 Positive, n,% 34, 26.8% 203, 30.4% 0.84 (0.55-1.28) Any PNS manifestation (n=34) No PNS manifestation (n=761) Odds Ratio (95%CI) MPP-1 Positive, n,% 11, 32.4% 226, 29.7% 1.13 (0.54-2.36) Any CN (n=10) No CN (n=785) Odds Ratio (95%CI) MPP-1 Positive, n,% 7, 70.0% 230, 29.3% 5.16 (1.44-18.54) * ACR NPSLE manifestations with onset within 10 years of SLE diagnosis and still present within the enrolment window, or occurred subsequently; no ‘exclusions’; not one of the NPSLE manifestations identified by Ainiala et al2. All 19 NPSLE manifestations were assessed individually and only the CNS and PNS subtypes where there was a difference between frequency of anti-MPP-1 positivity in patients with versus without the manifestation are shown.Bold indicates statistically significant result.Abstract 102 Table 2Comparison of baseline demographic and clinical characteristics of SLE patients with versus without cranial neuropathy within 5 years of follow-up Entire Cohort (n=795) With Cranial Neuropathy (n=10) Without Cranial Neuropathy- (n=785) Difference, 95%CI With vs without CN) Demographics Age at MPP-1 testing, years, mean ± SD 35.7 ± 13.5 37.0 ± 11.5 35.6 ± 13.5 1.4 (-7.1, 9.8) Age at diagnosis, years, mean ± SD 35.1 ± 13.5 36.4 ± 11.5 35.1 ± 13.5 1.4 (-7.1, 9.8) Sex,% Female 88.7% 80.0% 88.8% -8.8% (-33.7%, 16.1%) Ethnicity,% White 52.1% 60.0% 52.0% 8.0% (-22.5%, 38.6%) Clinical Characteristics SLEDAI-2K at enrolment, mean ± SD 5.7 ± 5.4 3.4 ± 5.7 5.7 ± 5.4 -2.3 (-5.7, 1.1) ACR Criteria Malar rash 33.0% 40.0% 32.9% 7.1% (-23.4%, 37.7%) Discoid rash 11.1% 0.0% 11.2% -11.2% (-13.4%, -9.0%) Oral ulcers 35.4% 20.0% 35.5% -15.5% (-40.6%, 9.5%) Serositis 27.8% 20.0% 27.9% -7.9% (-32.9%, 17.1%) Arthritis 70.4% 80.0% 70.3% 9.7% (-15.3%, 34.7%) Photosensitivity 33.8% 30.0% 33.9% -3.9% (-32.5%, 24.7%) Renal disorder 26.7% 20.0% 26.8% -6.8% (-31.7%, 18.2%) Neurologic disorder 4.4% 0.0% 4.5% -4.5% (-5.9%, -3.0%) Hematologic disorder 66.4% 90.0% 66.1% 23.9% (5.0%, 42.8%) Immunologic disorder 79.6% 80.0% 79.6% 0.4% (-24.6%, 25.3%) Antinuclear antibody 95.7% 100.0% 95.7% 4.3% (2.9%, 5.8%) Hypocomplementemia 42.8% 37.5% 42.8% -5.3% (-39.1%, 28.4%) Leukopenia 8.8% 0.0% 8.9% -8.9% (-11.0%, -6.8%) Other Serologic Markers Cardiolipin IgG 16.7% 11.1% 16.8% -5.7% (-26.4%, 15.1%) Cardiolipin IgM 5.7% 0.0% 5.7% -5.7% (-7.5%, -4.0%) ß2GP1 IgG 9.1% 0.0% 9.2% -9.2% (-11.3%, -7.0%) ß2GP1 IgM 11.5% 11.1% 11.5% -0.4% (-21.0%, 20.3%) Lupus anticoagulant 35.8%(n=95) 50.0%(n=2) 35.5%(n=93) 14.5% (-55.5%, 84.5%) anti-dsDNA 73.3% 88.9% 73.1% 15.8% (-5.0%, 36.6%) anti-Histones 31.1% 33.3% 31.1% 2.2% (-28.7%, 33.2%) anti-Ribosome P 25.9% 55.6% 25.5% 30.1% (-2.6%, 62.7%) anti-Sm 23.5% 22.2% 23.5% -1.3% (-28.6%, 26.1%) anti-Sm/RNP 28.6% 22.2% 28.7% -6.4% (-33.8%, 20.9%) anti-PCNA 17.8% 33.3% 17.6% 15.7% (-15.2%, 46.6%) anti-Ro52/TRIM21 39.2% 22.2% 39.4% -17.2% (-44.6%, 10.2%) anti-SSA/Ro60 43.9% 22.2% 44.1% -21.9% (-49.3%, 5.5%) anti-SSB/La 22.4% 22.2% 22.4% -0.1% (-27.5%, 27.2%) Bold indicates statistically significant result. Covariates with zero cells not included in multivariate analysis. Abbreviations: anti-dsDNA, anti-double-stranded DNA; anti-PCNA; anti-proliferating cell nuclear antigen; Anti- Sm/RNP; anti-Smith/ribonucleoprotein; Anti-Sm, anti-Smith; IgG; immunoglobulin G; IgM; immunoglobulin M; MPP-1, M-phase phosphoprotein 1; SD, standard deviation; SLE, systemic lupus erythematosus; SLEDAI, SLE disease activity index; TRIM, tripartite motif.Abstract 102 Table 3Multivariate analysis examining the association between MPP-1 positivity and cranial neuropathy within 5 years of follow-up Covariates* Cranial Neuropathy Positivity Odds Ratio (95%CI) Anti-MPP-1+ at baseline 5.24 (1.44, 19.09) Age at Anti-MPP-1 testing 1.01 (0.97, 1.06) Female 0.58 (0.13, 2.49) White ethnicity 1.44 (0.41, 5.07) Hematologic disorder 3.04 (0.54, 17.10) Antinuclear antibody 1.18 (0.07, 21.04) * Model covariates include MPP-1 positivity, adjusting for age at MPP-1 testing, female, White race/ethnicity, and significantly different clinical characteristics at baselineBold indicates statistically significant result
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- Title
- 102 M-Phase Phosphoprotein 1 (MPP-1) Autoantibodies as a Potential Biomarker for Cranial Neuropathies in an International SLE Inception Cohort
- Creators
- Eugene Krustev - University of CalgaryJohn G Hanly - Queen Elizabeth II Health Sciences CentreRicky Chin - University of CalgaryKatherine Buhler - University of CalgaryFrancesca Cardwell - University of WaterlooMurray B Urowitz - Toronto Western HospitalCaroline Gordon - University of BirminghamSang-Cheol Bae - University of BirminghamJuanita Romero-Diaz - Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránJorge Sanchez-Guerrero - Mount Sinai HospitalSasha Bernatsky - McGill University Health CentreDaniel J Wallace - Cedars-Sinai Medical CenterDavid A Isenberg - University College LondonAnisur Rahman - University College LondonJoan T Merrill - Oklahoma Medical Research FoundationPaul R Fortin - Université LavalDafna D Gladman - Queen Elizabeth II Health Sciences CentreIan N Bruce - Manchester Academic Health Science CentreMichelle Petri - Johns Hopkins MedicineEllen M Ginzler - SUNY Downstate Health Sciences UniversityMary Anne Dooley - University of North Carolina at Chapel HillRosalind Ramsey-Goldman - Northwestern UniversitySusan Manzi - Allegheny Health NetworkAndreas Jönsen - Lund UniversityGraciela S Alarcón - University of Alabama at BirminghamRonald F van Vollenhoven - University of Alabama at BirminghamCynthia Aranow - Feinstein Institute for Medical ResearchMeggan Mackay - Feinstein Institute for Medical ResearchGuillermo Ruiz-Irastorza - BioCruces Health research InstituteSam Lim - Emory UniversityMurat Inanc - Istanbul UniversityKenneth C Kalunian - University of California San DiegoSøren Jacobsen - RigshospitaletChristine A Peschken - University of ManitobaDiane L Kamen - Medical University of South CarolinaAnca Askanase - New York University Langone Orthopedic HospitalJill Buyon - New York UniversityMarvin J Fritzler - University of CalgaryAnn E Clarke - University of CalgaryMay Y Choi - University of Calgary
- Publication Details
- Lupus science & medicine, v 9(Suppl 3), pp A2-A3
- Publisher
- Lupus Foundation of America
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- General Internal Medicine
- Other Identifier
- 991021934009204721