HYDROXYCHLOROQUINE REDUCES THE TITERS OF ANTI-DOMAIN 1 ANTIBODIES OVER TIME IN PATIENTS WITH PERSISTENTLY POSITIVE ANTIPHOSPHOLIPID ANTIBODIES: RESULTS FROM THE APS ACTION CLINICAL DATABASE AND REPOSITORY (“REGISTRY”)
C. Chighizola1, F. Pregnolato1, D. Andrade2, M. Tektonidou3, S. Sciascia4, V. Pengo5, A. Ugarte6, H. M. Belmont7, M. Gerosa8, P. Fortin9, C. Lopez-Pedrera10, Z. Zhang11, T. Atsumi12, G. De Jesùs13, N. Kello14, D. W. Branch15, L. Andreoli16, D. Wahl17, M. A. Petri18, E. Rodríguez Almaraz19, R. Cervera20, G. Pons Estel21, J. Knight22, R. Willis23, M. Barber24, B. Artim Esen25, M. Efthymiou26, D. Erkan27, M. L. Bertolaccini28, on behalf of AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION)
1University of Milan, Pediatric Rheumatology Unit, ASST G. Pini - CTO, Milan, Italy
2University of Sao Paulo, Reumatologia, Sao Paulo, Brazil
3National and Kapodistrian University of Athens, First Department of Propaedeutic and Internal Medicine, Laiko Hospital, Athens, Greece
4University of Turin, Department of Clinical and Biological Sciences, Turin, Italy
5University of Padua, Department of Cardiac Thoracic and Vascular Sciences, Padua, Italy
6Universidad del País Vasco/Euskal Herriko Unibertsitatea, Unidad de Investigación de Enfermedades Autoinmunes, Servicio de Medicina Interna, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Spain
7New York University, Hospital for Joint Diseases, New York, United States of America
8University of Milan, Clinical Rheumatology Unit, Milan, Italy
9Université Laval, Medicine, Quebec, Canada
10University of Cordoba, ‘Systemic autoimmune diseases and chronic arthropathies’ IMIBIC-Reina Sofia Hospital, Cordoba, Spain
11Peking University First Hospital, Rheumatology and Immunology Department, Beijing, China
12Hokkaido University, Department of Rheumatology, Endocrinology and Nephrology Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
13Universidade do Estado do Rio de Janeiro, Department of Obstetrics, Rio de Janeiro, Brazil
14Northwell Health, Rheumatology, Great Neck, United States of America
15University of Utah and Intermountain Healthcare, Department of Obstetrics, Salt Lake City, United States of America
16University of Brescia, Rheumatology Unit, Brescia, Italy
17Nancy University, Internal Medicine, Nancy, France
18Johns Hopkins University School of Medicine, Rheumatology, Baltimore, United States of America
19Hospital Universitario, 12 de Octubre, Rheumatology, Madrid, Spain
20Hospital Clínic de Barcelona, Department of Autoimmune Diseases, Barcelona, Spain
21Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Rheumatology, Rosario, Argentina
22University of Michigan, Division of Rheumatology, Ann Arbor, United States of America
23University of Texas Medical Branch, Internal Medicine, Galveston, United States of America
24University of Calgary, Division of Rheumatology, Calgary, Canada
25University of Istanbul, Division of Rheumatology, Istanbul, Turkey
26University College London, Department of Haematology, London, United Kingdom
27Hospital for Special Surgery, Rheumatology, New York, United States of America
28King’s College London, Vascular Risk and Surgery Section, London, United Kingdom
Background: Data on fluctuation of antibodies directed against domain 1 (anti-D1) of β
2
-glycoprotein I (β
2
GPI) 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 anti-β
2
GPI levels.
Objectives: This project aims at evaluating predictors of the variation of 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 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-β
2
GPI and anti-D1 IgG were tested by chemiluminescence (BioFlash, Werfen) at APS ACTION core laboratories. Positive results were defined as >20 CU, according to the manufacturer. Clinical data were retrieved from APS ACTION online database. Anti-D1 titers within the same subject were compared by Friedman’s test. A mixed linear model was built to identify predictors of the fluctuation of anti-D1 antibody titers over time.
Results: In this longitudinal study, 230 patients with anti-D1 tested at 4 time points were included (
Table 1
). 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 at baseline 189.0; T1 132.3 [-15%]; T2 113.8 [-17%]; T3 109.2 [-6% versus T2, -38% versus T1]). Anti-D1 titers were significantly higher at baseline compared to T3 (p=0.029). In the 4 years of follow-up, 18 new thrombotic events occurred. Patients with double/triple aPL positivity displayed 12.5 fold increase [95%CI 7.4-20.0] in baseline anti-D1 titers. After adjustment for age, gender and number of positive aPL tests, the fluctuation of anti-D1 titers was associated with treatment with hydroxychloroquine (HCQ) at each time-point. In particular, treatment with HCQ, but not those with conventional immunosuppressors, was associated with a 1.3-fold decrease in anti-D1 titers [95%CI 1.1-1.5]. In the same multivariable model, incident vascular events were associated with a 1.5 fold increase of anti-D1 titers. A concomitant diagnosis of systemic lupus erythematosus did not affect the fluctuation of anti-D1 titers.
Demographic and Clinical Characteristics of 230 APS ACTION Registry Patients with anti-D1 tested ≥3 time points during the follow-up
Anti-D1 pos samples
Anti-D1 neg samples
p-value
Overall sample
(n=135)
(n=95)
(n=230)
Age [years]
mean (SD
)
42.3 (11.8)
48.8 (13.0)
0.0001
45.0 (12.7)
%Female
(n
)
71.9 (97)
65.3 (62)
0.358
69.1 (159)
Associated systemic autoimmune disease
39.3 (53)
44.2 (42)
0.539
41.3 (95)
aPL without APS
19.3 (26)
34.7 (33)
0.010
25.7 (59)
Thrombotic APS
54.1 (73)
53.7 (51)
53.9 (124)
Obstetric APS
11.9 (16)
5.3 (5)
9.1 (21)
Thrombotic/+obstetric APS
14.8 (20)
6.3 (6)
11.3 (26)
aCL IgG
89.5 (119/133)
25.5 (24/94)
<0.0001
63.0 (143/227)
aCL, IgM
36.1 (48/133)
27.7 (26/94)
0.234
32.6 (74/227)
Anti-2GPI, IgG
93.2 (124/133)
39.4 (37/94)
<0.0001
70.9 (161/227)
Anti-2GPI, IgM
34.6 (46/133)
21.3 (20/94)
0.043
29.1 (66/227)
LA
82.8 (82/99)
59.5 (44/74)
0.001
72.8 (126/173)
Conclusion: Treatment with HCQ and vascular events during follow-up were identified as significant predictors of the fluctuation of anti-D1 antibody titers over time.
Disclosure of Interests: None declared.
Citation: , volume 81, supplement 1, year 2022, page 484
Session: SLE, Sjön’s and APS - aetiology, pathogenesis and animal models
(POSTERS only)
