ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository ("Registry")

Irene Cecchi^{1

2}, Massimo Radin^{1

2}, Silvia Grazietta Foddai^{1

2}, Alice Barinotti^{1

2}, Danieli Andrade³, Maria G Tektonidou⁴, Vittorio Pengo⁵, Guillermo Ruiz-Irastorza⁶, H Michael Belmont⁷, Chary Lopez Pedrera⁸, Paul R Fortin⁹, Maria Gerosa¹⁰, Guilherme de Jesús¹¹, Tatsuya Atsumi¹², Lanlan Ji¹³, Maria Efthymiou¹⁴, D Ware Branch¹⁵, Cecilia Nalli¹⁶, Esther Rodriguez-Almaraz¹⁷, Michelle Petri¹⁸, Ricard Cervera¹⁹, Jason S Knight²⁰, Bahar Artim-Esen²¹, Rohan Willis²², Maria Laura Bertolaccini²³, Hannah Cohen¹⁴, Doruk Erkan²⁴, Savino Sciascia^{1

2}

Affiliations

¹ University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, Turin, Italy.
² Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
³ University of São Paulo, São Paulo, Brazil.
⁴ National and Kapodistrian University of Athens, Athens, Greece.
⁵ Senior Scientist, University of Padova, Italy.
⁶ Autoinmune Diseases Research Unit, Biobizkaia Health Research Institute, UPV/EHU, Barakaldo, Spain.
⁷ New York University Langone Medical Center, New York, NY, USA.
⁸ Rheumatology Service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Córdoba, Spain.
⁹ Centre ARThrite-CHU de Québec - Université Laval, Quebec, QC, Canada.
¹⁰ University of Milan, Milan, Italy.
¹¹ Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
¹² Hokkaido University Hospital, Sapporo, Japan.
¹³ Peking University First Hospital, Beijing, China.
¹⁴ University College London, London, UK.
¹⁵ University of Utah and Intermountain Healthcare, Salt Lake City, UT, USA.
¹⁶ University of Brescia, Brescia, Italy.
¹⁷ Hospital Universitario, 12 de Octubre, Madrid, Spain.
¹⁸ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁹ Department of Autoimmune Diseases, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia,Spain.
²⁰ University of Michigan, Ann Arbor, MI, USA.
²¹ Istanbul University School of Medicine, Istanbul, Turkey.
²² University of Texas Medical Branch, Galveston, TX, USA.
²³ School of Cardiovascular & Metabolic Medicine & Sciences, King's College London, London, UK.
²⁴ Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA.

PMID: 39423147
PMCID: PMC12225680
DOI: 10.1093/rheumatology/keae583

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository ("Registry")

Irene Cecchi et al. Rheumatology (Oxford). 2025.

. 2025 May 1;64(5):2862-2867.

doi: 10.1093/rheumatology/keae583.

Authors

Affiliations

¹ University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, Turin, Italy.
² Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
³ University of São Paulo, São Paulo, Brazil.
⁴ National and Kapodistrian University of Athens, Athens, Greece.
⁵ Senior Scientist, University of Padova, Italy.
⁶ Autoinmune Diseases Research Unit, Biobizkaia Health Research Institute, UPV/EHU, Barakaldo, Spain.
⁷ New York University Langone Medical Center, New York, NY, USA.
⁸ Rheumatology Service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Córdoba, Spain.
⁹ Centre ARThrite-CHU de Québec - Université Laval, Quebec, QC, Canada.
¹⁰ University of Milan, Milan, Italy.
¹¹ Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
¹² Hokkaido University Hospital, Sapporo, Japan.
¹³ Peking University First Hospital, Beijing, China.
¹⁴ University College London, London, UK.
¹⁵ University of Utah and Intermountain Healthcare, Salt Lake City, UT, USA.
¹⁶ University of Brescia, Brescia, Italy.
¹⁷ Hospital Universitario, 12 de Octubre, Madrid, Spain.
¹⁸ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁹ Department of Autoimmune Diseases, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia,Spain.
²⁰ University of Michigan, Ann Arbor, MI, USA.
²¹ Istanbul University School of Medicine, Istanbul, Turkey.
²² University of Texas Medical Branch, Galveston, TX, USA.
²³ School of Cardiovascular & Metabolic Medicine & Sciences, King's College London, London, UK.
²⁴ Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA.

PMID: 39423147
PMCID: PMC12225680
DOI: 10.1093/rheumatology/keae583

Abstract

Objectives: This study focused on the prevalence and impact of ANA in aPL-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs).

Methods: Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry. Patients with concomitant SARDs were excluded.

Results: A total of 430 aPL-positive patients were included in the analysis, 56% ANA-positive (ANA+) and 44% ANA-negative (ANA-). ANA positivity was significantly associated with history of haematologic manifestations (persistent autoimmune haemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA+ vs 7% of ANA-, P = 0.006). Triple aPL-positivity was more frequent in the ANA+ subgroup (P = 0.02), along with low baseline C3 and C4 levels (P = 0.05 and P = 0.009, respectively), and higher frequency for ENA. Among aPL-positive patients with no APS classification, ANA+ patients showed a higher rate of arthritis (P = 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA+ and 96 were ANA-; ANA- patients had a higher number of pregnancies (P = 0.018), and number of live births (P = 0.014). A wider proportion of ANA+ patients were treated with HCQ (P < 0.001).

Conclusion: When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA+ patients showed higher rates of systemic autoimmune features, including haematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA- had a higher rate of pregnancies and live births.

Keywords: antinuclear antibodies; antiphospholipid antibodies; antiphospholipid syndrome; phenotyping.

© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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References

1. Barbhaiya M, Zuily S, Naden R et al. ; ACR/EULAR APS Classification Criteria Collaborators. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol 2023;75:1687–702. - PubMed
1. Radic M, Pattanaik D. Cellular and molecular mechanisms of anti-phospholipid syndrome. Front Immunol 2018;9:969. - PMC - PubMed
1. Meroni PL, Borghi MO, Grossi C et al. Obstetric and vascular antiphospholipid syndrome: same antibodies but different diseases? Nat Rev Rheumatol 2018;14:433–40. - PubMed
1. Tincani A, Andreoli L, Chighizola C et al. The interplay between the antiphospholipid syndrome and systemic lupus erythematosus. Autoimmunity 2009;42:257–9. - PubMed
1. Miyakis S, Lockshin MD, Atsumi T et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295–306. - PubMed

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ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository ("Registry")

Affiliations

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository ("Registry")

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