Heterogeneity of antiphospholipid antibody profiles in a clinical cohort and association with distinct clinical features

Q: Why do some APS patients become classified as “seronegative APS”?

APS criteria rely on standard antibodies (LAC, aCL IgG/IgM, and β2GPI IgG/IgM). Patients with typical clinical features but negative results for these standard antibodies are often categorized as seronegative APS.

Q: What extended antibody profile was evaluated in this study?

The study tested an extended profile in addition to criteria antibodies, including antiphosphatidylserine/prothrombin complex (aPS/PT) IgG/IgM and aCL/β2GPI IgA.

Q: Which antibody marker showed the strongest diagnostic and clinical association?

aPS/PT-IgM emerged as a strong independent serological marker, predicting clinical diagnosis and showing diagnostic performance for triple-negative APS, while standard criteria antibodies lost independent significance in the full model.

Sep 29, 2026

Uploaded by Grenda

Background and objective: Standard antiphospholipid syndrome (APS) diagnosis uses lupus anticoagulant, anticardiolipin (aCL) IgG/IgM, and β2-glycoprotein I (β2GPI) IgG/IgM, which can miss “seronegative APS.” This study clarifies the diagnostic and risk-stratification value of extended antibodies including aPS/PT and aCL/β2GPI IgA. Methods: 2994 suspected APS patients underwent criteria and extended antibody testing; principal component analysis, multivariate logistic regression, and ROC evaluation were performed. Results: Three antibody dimensions explained 73.56% variance; aPS/PT-IgM predicted clinical diagnosis and triple-negative APS, and distinct clinical phenotypes were defined. Conclusion: APS antibody heterogeneity forms classical, inflammatory, and restricted subtypes; adding aPS/PT-IgM could reduce misdiagnosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

APS overview and diagnostic criteria

Seronegative APS and non-criteria antibodies

What is already known on this topic

What this study adds

How this study might affect research, practice or policy

Autoimmunity To cite: Shen Z, Yang S, Jin S, et al. Heterogeneity of antiphospholipid antibody profiles in a clinical cohort and association with distinct clinical features. RMD Open 2025;11:e006406 . doi:10 . 1136/ rmdopen-2025-006406 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[rmdopen-2025-006406](rmdopen-2025-006406)) . Received 30 September 2025 Accepted 14 December 2025 © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. 1Institute of Medical Technology, Peking University Health Science Center, Beijing, China 2Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China 3Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China Correspondence to Dr Liyan Cui; [cliyan@163.com](cliyan@163.com) ORIGINAL RESEARCH Heterogeneity of antiphospholipid antibody profiles in a clinical cohort and association with distinct clinical features Zhongjun Shen ,1,2,3 Shuo Yang,2,3 Shangjia Jin,2,3 Qi Liu,2,3 He Wang,2,3 Yuying Nie,2,3 Huike Guo,1,2,3 Liyan Cui1,2,3 ABSTRACT Background The diagnosis of antiphospholipid syndrome (APS) uses standard antibodies (lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, β2-glycoprotein I antibodies (β2GPI) IgG/IgM), which results in some patients with ‘seronegative APS’ being overlooked. The diagnostic value of an extended antibody profile, including antiphosphatidylserine/prothrombin complex (aPS/PT) andaCL/β2GPI IgA, requires clarification. Objective This study aimed to define antibody heterogeneity in APS and determine the diagnostic and risk-stratification value of novel antibodies. Methods We retrospectively enrolled 2994 patients with clinical features suggestive of APS who underwent testing for criteria antibodies (LAC, aCL IgG/IgM and β2GPI IgG/IgM) and extended markers (aPS/PT IgG/IgMand aCL/β2GPI IgA). Principal component analysis (PCA) explored antibody reactivity patterns. Multivariate logistic regression identified independent diagnostic predictors, and receiver operating characteristic curve analysis evaluated diagnostic performance. Associations between antibodies and clinical parameters defined clinical phenotypes. Results PCA revealed three dimensions explaining 73.56% of variance: principal component (PC)1 (IgG/LAC axis; 41 .42%), PC2 (specific IgM axis; 18. 12%) and PC3 (specific IgA axis; 14.02%) . aPS/PT-IgM was a strong independent predictor of clinical diagnosis (adjusted OR 1 . 147, 95% CI 1.129 to 1 . 165, p<0 .001) . The area under the curve for diagnosing triple-negative APS was 0.868 for aPS/PT-IgM. Standard criteria antibodies lost independent significance in the full model. Phenotypic analysis identified three subtypes: a ‘classical type’(PC1-High) with prolonged coagulation times and complement consumption; an ‘inflammatory type’(PC3-High) with elevated systemic inflammation markers without complement consumption; and a ‘restricted type’(PC2-High) associated with anaemia. Conclusion Distinct antiphospholipid antibody heterogeneity exists, categorisable into ‘classical’,‘inflammatory’ and ‘restricted’ subtypes. This study identifies aPS/PT-IgM as a strong independent serological marker associated with clinical status. Incorporating aPS/ PT-IgM into routine testing could significantly reduceseronegative APS misdiagnosis. WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Current antiphospholipid syndrome (APS) diagnosis relies on a limited panel of standard antibodies, leaving many patients with typical symptoms classified as ‘seronegative’. Non-criteria antibodies such as antiphosphatidylserine/prothrombin complex (aPS/PT) have been proposed as additional biomarkers, but their independent diagnostic value and ov

FAQs

Why do some APS patients become classified as “seronegative APS”?

APS criteria rely on standard antibodies (LAC, aCL IgG/IgM, and β2GPI IgG/IgM). Patients with typical clinical features but negative results for these standard antibodies are often categorized as seronegative APS.

What extended antibody profile was evaluated in this study?

The study tested an extended profile in addition to criteria antibodies, including antiphosphatidylserine/prothrombin complex (aPS/PT) IgG/IgM and aCL/β2GPI IgA.

Which antibody marker showed the strongest diagnostic and clinical association?

aPS/PT-IgM emerged as a strong independent serological marker, predicting clinical diagnosis and showing diagnostic performance for triple-negative APS, while standard criteria antibodies lost independent significance in the full model.

Sep 29, 2026

Uploaded by Grenda