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Insights on Antiphospholipid antibody syndrome metabolomics by NMR

1Biological Chemistry Laboratory, Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, 2Hemostasis and Thrombosis Laboratory, Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, 32Hemostasis and Thrombosis Laboratory, Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, 4School of Medical Sciences of the University of Campinas, Campinas, Sao Paulo, Brazil

Abstract Number: PB0413

Meeting: ISTH 2022 Congress

Theme: Venous Thromboembolism » Antiphospholipid Syndrome

Background: Antiphospholipid antibody syndrome (APS) is an acquired autoimmune thrombophilia that causes arterial, venous or microvascular thrombosis, and pregnancy morbidity, such as recurrent abortion, late fetal death, and severe preeclampsia. APS is diagnosed based on clinical and antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein I.

Aims: This study aimed to map serum signatures by NMR, and investigate if there is a connection among variation in metabolites and APS.

Methods: Individuals with APS (n = 32, Table 1) were analyzed, matched by age and gender with control individuals (HC, n =32, Table 1) to ensure homogeneity in the basal metabolic rates. The NMR data sets were recorded on Bruker AVANCE III 600 MHz spectrometer using the inverse triple-core probe at 25 °C. 1H-NMR data were processed, normalized by the sum, centered on the mean, and analyzed in MetaboAnalyst 5.0 software platform.

Results: The Partial Least Squares – Discriminant Analysis (PLS-DA, Fig. 1. A) and ortho-PLS-DA (Fig. 1. B) performed onto CPMG data enabled us to distinguish between the APS and HC groups. The main metabolites related to APS were identified based on multi and univariate analysis results (Fig. 1.C). APS-individuals showed lower serum amounts of lipids, glutamine (Gln), lysine (Lys), and valine (Val), while the amounts of isoleucine (Ile), and threonine (Thr) were slightly higher compared to HC-individuals. Recently, in an animal model study, it was shown that Val and Ile metabolic pathways showed the major roles in regulating platelet activation in thrombosis.

Conclusion(s): The modified levels of those branched chain amino acids might be associated with the risk of APS, and it is still to verify if amino acids – Gln, Lys, Val, Ile, and Thr are potential targets for illuminating previously unknown pathways in APS, which open up possibilities for further studies.

The Ethics Research Committee approved the experimental procedures.

Figure 1.

Figure 1. APS serum metabolomics data. A. PLS-DA scores in PC 1 vs. PC 2 on CPMG data -Accuracy: 0.87, R2: 0.99, Q2: 0.42- B. oPLS-DA scores -R2Y: 0.99 and Q2: 0.45-. C. Identified serum metabolites that distinguish APS -red- from HC -blue- individuals, with p-value < 0.02

Table 1

Table 1. Demographic and clinical characteristics of studied cohort

To cite this abstract in AMA style:

Martins L, Honorato M, Montalvão S, Braga E, Silva L, de Paula E, Orsi F, Tasic L, Annichino-Bizzacchi J. Insights on Antiphospholipid antibody syndrome metabolomics by NMR [abstract]. https://abstracts.isth.org/abstract/insights-on-antiphospholipid-antibody-syndrome-metabolomics-by-nmr/. Accessed September 24, 2023.

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