Natural History and Clinical Implications of Lupus Autoantibodies in Primary Antiphospholipid Antibody Positive Patients: Results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”)

Rohan Willis¹, Anne Tebo², Leslie Skeith³, Nina Kello⁴, H Michael Belmont⁵, Paul Fortin⁶, Guilherme Ramires de Jesús⁷, David Branch⁸, Michelle Petri⁹, Jason Knight¹⁰, Reyhan Kose Cobanoglu¹¹, Maria Laura Bertolaccini¹², Hannah Cohen¹³, Robert Roubey¹⁴, Doruk Erkan¹⁵ and Danieli Andrade¹⁶, and on behalf of APS ACTION, ¹University of Texas Medical Branch, Galveston, TX, ²Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, ³University of Calgary, Calgary, ON, Canada, ⁴Northwell Health, Brooklyn, NY, ⁵NYU School of Medicine, New York, NY, ⁶Centre ARThrite - CHU de Québec - Université Laval, Quebec, QC, Canada, ⁷Universidade do Estado do Rio de Janeiro, Rio De Janeiro, Brazil, ⁸University of Utah and Intermountain Healthcare, Salt Lake City, UT, ⁹Johns Hopkins University School of Medicine, Timonium, MD, ¹⁰University of Michigan, Ann Arbor, MI, ¹¹Aydin Adnan Menderes University School of Medicine, Hospital for Special Surgery, NY, USA, Aydin, Turkey, ¹²King's College London, London, United Kingdom, ¹³University College London Hospitals NHS Foundation Trust, London, United Kingdom, ¹⁴Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC, ¹⁵Hospital for Special Surgery, New York, NY, ¹⁶University of São Paulo, São Paulo, SP, Brazil

Meeting: ACR Convergence 2024

Keywords: antiphospholipid syndrome, Autoantibody(ies), Biomarkers, Systemic lupus erythematosus (SLE)

Session Information

Date: Saturday, November 16, 2024

Title: Antiphospholipid Syndrome Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are characterized by heterogenous clinical presentations, driven by autoantibodies; patients with SLE develop APS more often than the reverse. The aim of this study was to determine the prevalence and clinical associations of SLE autoantibodies in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases (SARDs).

Methods: A web-based data capturing system is used to store patient clinical information and registry inclusion criteria are positive aPL (Revised Sapporo APS Classification Criteria), tested at least twice within one year prior to enrollment. Earliest available sera from North and South American registry patients with or without APS classification, but with no other SARDs (primary aPL/APS), were tested for IgG, IgM, IgA anticardiolipin (aCL) and anti-β₂glycoprotein I (aβ₂GPI) antibodies as well as anti-nuclear antibody (ANA), anti-dsDNA, anti-SSA, anti-SSB, anti-Sm, and anti-RNP antibodies using Phadia EliA^® fluorescence enzyme immunoassays (Thermofisher). Autoantibody prevalence and titers were compared in three groups: 1) patients with microvascular (aPL nephropathy, livedoid vasculopathy, and/or diffuse alveolar hemorrhage) and/or hematologic disease (immune thrombocytopenia and/or autoimmune hemolytic anemia) with/without thrombotic APS (TAPS) or obstetric APS (OAPS); 2) TAPS and/or OAPS but no microvascular or hematologic disease; and c) all aPL-positive patients not included in groups 1 and 2. The association of lupus antibodies with baseline clinical and laboratory characteristics was evaluated through pairwise univariate analyses.

Results: Of 230 patients included (median age at registry entry 45.0 interquartile range (IQR) 34.2-55.0 years, 73.9% female) (Group 1: 58 patients, Group 2: 126, and Group 3: 46), SLE antibody prevalence ranged from 0 to 18%: anti-dsDNA 41 (18%), ANA 39 (17%), anti-SSA 27 (12%), anti-SSB 5 (2%), anti-RNP 2 (1%), and anti-Sm 0 (0%) (Table 1). Anti-dsDNA titers, and the prevalence and titers of IgG aCL and IgG aβ₂GPI were significantly higher in patients with microvascular and/or hematologic disease. Clinical associations of SLE autoantibodies were: a) anti-dsDNA positivity with immune thrombocytopenia (odds ratio [OR] 95%CI: 3.0 [1.4-6.3], p=0.004), low C3 levels (OR 4.4 [1.4-13.3], p=0.007), and IVIG use (ever) (OR 4.2 [1.3-13.9], p=0.014); b) ANA positivity with low C3 (OR 4.7 [1.5-14.4], p=0.005) and hydroxychloroquine (HCQ) use (ever) (OR 2.1 [1.1-4.2], p=0.036); and c) anti-SSA positivity with low C3 (OR 3.6 [1.1-12.1], p=0.034) and HCQ use (OR 2.3 [1.0-5.1], p=0.044).

Conclusion: In primary aPL-positive patients with or without APS, the prevalence of SLE autoantibodies ranged from 0% to 18%, with anti-dsDNA, ANA and anti-SSA being most frequent and anti-Sm absent. Anti-dsDNA titers as well as IgG aCL/aβ₂GPI levels and prevalence were significantly higher in patients with microvascular and/or hematologic disease, compared to other aPL-positive patients. Low complement values, immune thrombocytopenia, HCQ, and IVIG use in primary aPL-positive patients were associated with at least one SLE autoantibody.

Table 1: Demographic and Laboratory Characteristics of Primary aPL/APS Patients with Microvascular, Hematologic, Macrovascular, Obstetric Disease and patients without these manifestations

Table 2: Clinical and Laboratory Associations of SLE type autoantibodies in Primary aPL/APS Patients (Odds Ratios (95% confidence Intervals)

Disclosures: R. Willis: Louisville APL Diagnostics Inc, 2, 8; A. Tebo: Euroimmun US, 6; L. Skeith: CSL Behring, 5, Leo Pharma, 6; N. Kello: None; H. Belmont: Alexion, 1, Aurinia, 6; P. Fortin: AstraZeneca, 2, 6, GlaxoSmithKlein(GSK), 2, 6, Moderna, 2; G. Ramires de Jesús: None; D. Branch: UCB Pharma Inc, 5; M. Petri: Amgen, 2, AnaptysBio, 2, Annexon Bio, 2, Arthros-FocusMedEd, 6, AstraZeneca, 2, 5, Atara Biosciences, 2, Aurinia, 5, 6, Autolus, 2, Avoro Ventures, 2, Biocryst, 2, Boxer Capital, 2, Cabaletto Bio, 2, Caribou Biosciences, 2, CTI, 1, CVS Health, 1, Eli Lilly, 2, 5, Emergent Biosolutions, 1, Ermiium, 2, Escient Pharmaceuticals, 2, Exagen, 5, Exo Therapeutics, 2, Gentibio, 2, GlaxoSmithKlein(GSK), 2, 5, iCell Gene Therapeutics, 2, Innovaderm Research, 2, IQVIA, 1, Janssen, 5, Kira Pharmaceuticals, 2, Merck/EMD Serono, 1, Nexstone Immunology, 2, Nimbus Lakshmi, 2, Novartis, 2, PPD Development, 2, Precision Biosciences, 2, Proviant, 2, Regeneron Pharmaceuticals, 2, Sanofi, 2, Seismic Therapeutic, 2, Senti Bioscienes, 2, Sinomab Biosciences, 2, Takeda, 2, Tenet Medicines Inc, 2, TG Therapeutics, 2, UCB, 2, Vertex Pharmaceuticals, 2, Worldwide Clinical Trials, 1, Zydus, 2; J. Knight: ArgenX, 1, Visterra/Otsuka, 1, 2; R. Kose Cobanoglu: None; M. Bertolaccini: None; H. Cohen: argenx, 1, GlaxoSmithKlein(GSK), 6, Roche, 1, Technoclone (paid to Univ Coll London Hosp Charity), 6, UCB (paid to Univ College London Hosp Charity), 2; R. Roubey: None; D. Erkan: ACR, 5, APS ACTION, 4, Argenx, 1, Cadrenal, 2, Chugai, 1, EULAR, 5, Exagen, 5, GlaxoSmithKlein(GSK), 2, 5, 6, Kyverna, 1, NIH, 5, Otsuka/Visterra, 1, Up-To-Date, 9; D. Andrade: None.

To cite this abstract in AMA style:

Willis R, Tebo A, Skeith L, Kello N, Belmont H, Fortin P, Ramires de Jesús G, Branch D, Petri M, Knight J, Kose Cobanoglu R, Bertolaccini M, Cohen H, Roubey R, Erkan D, Andrade D. Natural History and Clinical Implications of Lupus Autoantibodies in Primary Antiphospholipid Antibody Positive Patients: Results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”) [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/natural-history-and-clinical-implications-of-lupus-autoantibodies-in-primary-antiphospholipid-antibody-positive-patients-results-from-the-antiphospholipid-syndrome-alliance-for-clinical-trials-and-in/. Accessed .

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