Plasma protein profile in patients with antiphospholipid syndrome and controls without antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a thrombotic autoimmune disease associated with persistent presence of antiphospholipid antibodies. A range of mechanisms have been implicated in the clinical manifestations of APS, but it is unclear which processes are dominant in vivo, although all mechanisms take place in the circulation. Exploring the plasma protein profile may provide leads for further research.

This study assessed plasma protein abundances in patients with clinically stable APS compared with controls without APS across 2 cohorts.

The discovery cohort included 61 APS patients and 19 controls, and the verification cohort included 77 APS patients and 49 controls. Quantitative protein mass spectrometry was used to measure 159 plasma proteins, including proteins involved in blood coagulation, complement pathway, transport, apolipoproteins, and immunity. Proteins were quantified in plasma with use of stable isotope-labeled peptide standards. Data were analyzed using a Welch t-test. Ten proteins with the lowest P value from the discovery cohort were selected for validation in the verification cohort.

Of the 10 selected proteins, 6 were differentially abundant between APS patients and controls without APS in the verification cohort and showed consistent fold changes across both cohorts: alpha-1-acid glycoprotein 1, beta-2-microglobulin, complement C2, insulin-like growth factor-binding protein complex acid labile subunit, leucine-rich alpha-2-glycoprotein 1, and cystatin-C.

We identified 6 plasma proteins that were differentially abundant in APS patients compared with controls without APS and confirmed these associations in an independent verification cohort. Collectively, these proteins may reflect subclinical inflammation and renal involvement in APS.