Anti-Domain 1 Antibody Fluctuation over Time in Patients with Persistently Positive Antiphospholipid Antibodies: Results from the Aps Action Clinical Database and Repository (“Registry”)

Cecilia Chighizola¹, Francesca Pregnolato², Danieli De Andrade³, Maria Tektonidou⁴, Vittorio Pengo⁵, Amaia Ugarte⁶, H. Michael Belmont⁷, Paul R Fortin⁸, Tatsuya Atsumi⁹, Maria Efthymiou,¹⁰, Guilherme Ramires de Jesus¹¹, D. Ware Branch¹², Cecilia Nalli¹³, Michelle Petri¹⁴, Esther Rodriguez-Almaraz¹⁵, Ricard Cervera¹⁶, Yu Zuo¹⁷, Rohan Willis¹⁸, Elisa Bison¹⁹, Ian Mackie²⁰, Hannah Cohen²¹, Robert Roubey²², Doruk Erkan²³ and Maria Laura Bertolaccini²⁴, ¹University of Milan, Milan, Italy, ²Università degli Studi di Milano, Milan, Italy, ³University of São Paulo, São Paulo, Brazil, ⁴Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Joint Rheumatology Program, Laiko Hospital, Athens, Greece, ⁵Padova University Hospital, Padova, Italy, ⁶Hospital Universitario Cruces, Barakaldo, Spain, ⁷NYU School of Medicine, New York, NY, ⁸CHU de Quebec - Universite Laval, Québec City, QC, Canada, ⁹Hokkaido University, Sapporo, Japan, ¹⁰Haemostasis Research Unit, Department of Haematology, University College London, London, United Kingdom, ¹¹Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, ¹²University of Utah, Salt Lake City, UT, ¹³ASST SPEDALI CIVILI DI BRESCIA, Brescia, Italy, ¹⁴Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁵Hospital Universitario 12 de Octubre, Madrid, Spain, ¹⁶Hospital Clinic Barcelona, Barcelona, Spain, ¹⁷University of Michigan, Ann Arbor, MI, ¹⁸University of Texas Medical Branch, Galveston, TX, ¹⁹University of Padova, Padova, Italy, ²⁰University College London, London, United Kingdom, ²¹Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom, ²²UNC, Chapel Hill, NC, ²³Hospital for Special Surgery, New York, NY, ²⁴King's College London, London, United Kingdom

Meeting: ACR Convergence 2021

Keywords: antiphospholipid syndrome, Autoantibody(ies), Biomarkers

Session Information

Date: Saturday, November 6, 2021

Title: Antiphospholipid Syndrome Poster (0069–0083)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Data on fluctuation of antibodies against domain 1 (anti-D1) of β₂-glycoprotein I (β₂GPI) are scarce. Patients with antiphospholipid syndrome (APS) and all three criteria tests for antiphospholipid antibodies (aPL) display higher titers of anti-D1, which correlate with aβ₂GPI levels. This project aims at evaluating anti-D1 titers over time in a large international cohort of persistently aPL positive patients.

Methods: AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Registry was created to study the course of persistently aPL-positive patients with or without autoimmune disorders over at least 10 years. Inclusion criteria are positive aPL by Updated Sapporo Criteria tested within one year prior to enrolment. Patients are followed up every 12±3 months with clinical data and blood collection. Patients with available blood samples from at least three time points were included in this analysis. Anti- β₂GPI and anti-D1 IgG were tested by chemiluminescence (BioFlash, INOVA Diagnostics) at APS ACTION core laboratories. Positive results were defined as >20 CU. Clinical data were retrieved from APS ACTION online database. Anti-D1 titers within the same subject were compared by Friedman’s test. The association between categorical and continuous variables was assessed by chi-squared and Spearman’s tests.

Results: In this longitudinal study, 1942 samples from 515 patients were tested for anti-D1 and aβ2GPI IgG; 230 patients with anti-D1 tested at ≥3 time points were included (Table). Patients with thrombotic APS had anti-D1 titers significantly higher than those without thrombosis (p=0.022). Among 135 patients with at least one anti-D1 positive result, anti-D1 titers varied significantly over time (Friedman statistics: 508.5, p< 0.0001; anti-D1 geometric mean [95%CI] at baseline 189.0 [115.9-308.3]; T1 132.3 [81.1-215.8]; T2 113.8 [69.8-185.5]; T3 109.2 [66.9-178.1]. Anti-D1 titers were significantly higher at baseline compared to T3 (p=0.029). Over time, anti-D1 titers significantly decreased in 107 patients, and increased in 28 (p< 0.0001). In 11.3% of patients, anti-D1 results changed from positive to negative (n: 20), or negative to positive (n: 6). (Mc Nemar’s χ2=6.5; p=0.011). Anti- β2GPI titers correlated with anti-D1 titers and significantly reduced at T3 compared to baseline (aβ2GPI at baseline 187.1 [14.5-1586.5]; T1 150.8 [11.1-1379.2]; T2 124.9 [12.2-1304]; T3 117.6 [8.7-1136.6]; Friedman statistics=11.32, p=0.010).

Conclusion: Anti-D1 antibodies vary significantly overtime and approximately 10% may become negative during follow up. Our future analysis of the registry will demonstrate the clinical relevance of this variation, and the impact of treatment.

Table.

Disclosures: C. Chighizola, None; F. Pregnolato, None; D. De Andrade, None; M. Tektonidou, None; V. Pengo, None; A. Ugarte, None; H. Belmont, None; P. Fortin, Lilly, 1, AbbVie, 1, AstraZeneca, 1; T. Atsumi, AbbVie Japan GK, 2, 6, Astellas Pharma Inc., 5, 6, Bristol-Myers Squibb Co. Ltd, 6, Chugai Pharmaceutical Co. Ltd, 5, 6, Daiichi Sankyo Co. Ltd, 5, 6, Eisai Co. Ltd., 6, Eli Lilly Japan K.K, 6, Mitsubishi Tanabe Pharma Co.;, 5, 6, Pfizer Japan Inc, 2, 5, 6, Takeda Pharmaceutical Co. Ltd, 5, 6, UCB Japan Co. Ltd, 6, AstraZeneca plc, 2, Boehringer Ingelheim Co. Ltd, 2, Medical & Biological Laboratories Co. Ltd, 2, Novartis Pharma K.K, 2, Ono Pharmaceutical Co. Ltd, 2, Alexion Inc, 5, Otsuka Pharmaceutical Co., Ltd, 5, Gilead Sciences, Inc., 5, 6; M. Efthymiou,, None; G. de Jesus, None; D. Branch, UCB Pharmaceuticals, 1, 5; C. Nalli, None; M. Petri, Alexion, 1, Amgen, 1, Astrazeneca, 1, 5, Aurinia, 5, 6, Eli Lilly, 5, Emergent Biosolutions, 1, Exagen, 5, Gilead Biosciences, 2, GSK, 1, 5, IQVIA, 1, Idorsia Pharmaceuticals, 2, Janssen, 1, 5, Merck EMD Serono, 1, Momenta Pharmaceuticals, 2, PPD Development, 1, Sanofi, 2, Thermofisher, 5, UCB Pharmaceuticals, 2; E. Rodriguez-Almaraz, None; R. Cervera, None; Y. Zuo, None; R. Willis, Louisville APL Diagnostic Inc, 2; E. Bison, None; I. Mackie, None; H. Cohen, Bayer Healthcare, 5, 6, 12, Support to attend scientific meetings; Honoraria for lectures at symposia paid to University College London Hospitals Charity, UCB Biopharma, 2, 12, Consultancy fees paid to University College London Hospitals Charity; R. Roubey, None; D. Erkan, ACR/EULAR, 5, LCTC, 5, NIH/NIAID, 5, GSK, 5, 6, Exagen, 5, Alexion, 2, UCB, 2, UpToDate, 9, APS ACTION, 4; M. Bertolaccini, None.

To cite this abstract in AMA style:

Chighizola C, Pregnolato F, De Andrade D, Tektonidou M, Pengo V, Ugarte A, Belmont H, Fortin P, Atsumi T, Efthymiou, M, de Jesus G, Branch D, Nalli C, Petri M, Rodriguez-Almaraz E, Cervera R, Zuo Y, Willis R, Bison E, Mackie I, Cohen H, Roubey R, Erkan D, Bertolaccini M. Anti-Domain 1 Antibody Fluctuation over Time in Patients with Persistently Positive Antiphospholipid Antibodies: Results from the Aps Action Clinical Database and Repository (“Registry”) [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/anti-domain-1-antibody-fluctuation-over-time-in-patients-with-persistently-positive-antiphospholipid-antibodies-results-from-the-aps-action-clinical-database-and-repository-registry/. Accessed .

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