Latest Research on Antiphospholipid Syndrome (2024 Edition)

The bad news about Antiphospholipid Syndrome (APS) is that it’s chronic. The good news is that there are quite a number of exciting new treatments in the works. This article is part of the APS resource library that I’m building up on the site for patients, as a patient who has lived with it for more than 20 years myself.

This post will focus on the latest research on Antiphospholipid Syndrome as of 2024, and I aim to update it as frequently as I can. The ultimate A – Z resource guide on Antiphospholipid Syndrome is taking me longer to compile (years, in fact!), and will be out soon. I thought I’d release this post first, or it might become outdated by then. Don’t forget to check the blog again for its release. Alternatively, you can sign up for my newsletter here or at the end of the post, to ensure that you receive all updates.

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

Last Updated:
• 7 June 2024: Discovery of 2 Missing Enzymes in People with Antiphospholipid Syndrome

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Personal Research is Important as a Patient

Before I begin, I just wanted to emphasise that it is important that you do your own research as a patient with Antiphospholipid Syndrome. This can feel like a colossal task in the beginning, with a long list of foods, drinks, medications and activities that you need to moderate. It took me a long time to figure out what works for me through trial and error, often unwittingly. But trust me, you will learn over time, and become more confident with living with this autoimmune disease. Knowledge is power, and doing your own research on Antiphospholipid Syndrome in relation to its impact on your personal life can also help to make you feel more empowered.

There are also a few things you can do online to ensure that you don’t miss out on the latest research on Antiphospholipid Syndrome. I personally subscribe to Google Alerts for keywords related to: “Antiphospholipid Syndrome”, “Lupus”, “autoimmune disease”, “chronic illness” and the likes.

Another tool I use is Feedly, an RSS (Really Simple Syndication) feed, where I subscribe to specific websites and news to browse through on a daily basis. If you’re curious as to how an RSS feed looks like, this is the one for this website. You simply need to add the URL to Feedly, and everything published on my blog will be in your reader. The best part is that these tools are free to use, and you can add any other topic that you’re interested in as well!

Finally, I also rely quite a bit on Google Scholar to learn more about various aspects of Antiphospholipid Syndrome from a medical and scientific perspective. In fact, all of the latest research on Antiphospholipid Syndrome that you will read about in this post can be found on Google Scholar – so it is indeed possible to keep up with the research on your own, too! There are many websites on ‘regular’ Google search, but it’s important to note that not all of these sources are verified, whereas articles on Google Scholar are. If you do choose to do your own research via ‘regular’ Google, do ensure that the source is from an established organisation, such as the NHS or Cleveland Clinic.

A Breakdown of the Latest Research on Antiphospholipid Syndrome

Whilst there are quite a number of promising new research and clinical trials for Antiphospholipid Syndrome, it is still a rare disease that could use more public awareness and research funding. The American College of Rheumatology (ACR) holds an annual convergence that showcases the latest research and knowledge into all areas of rheumatology. Here are the new Antiphospholipid Syndrome findings that were presented at the ACR convergence in 2023, and I can’t wait to see what will be shared in the next one in November 2024!

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Peptide Libraries for Diagnosing Antiphospholipid Syndrome

Let’s begin with exciting new advancements in the diagnosis stage of APS. The current tests available for the detection of autoantibodies that target prothrombin (aPT) are aPS/PT, and aPT-A assays. However, it has been difficult to standardise their detection in lab tests, due to variability in platforms and protocols.

One new diagnostic tool in the works is a novel ELISA assay, ProTS525A-Biot (aPT-Bio). In a study of 27 high-risk APS patients, the ProTS525A-Biot was able to identify 24 triple-positive APS patients. ProTS525A-Biot may also be useful in future for the detection of other prothrombotic conditions apart from APS, such as COVID-19 (Chinnaraj et al., 2021).

Another diagnostic tool in the works is based on peptide IIa‐8.0‐biot‐2x, which is able to interact with antiphospholipid antibodies (aPLs) to a much larger extent (Moghbel et al., 2022).

Research on B Cells & T Cells in Autoimmune Diseases

If you live with an autoimmune disease, chances are that you’ve heard of T cells and B cells, and might even have underwent a biologic infusion to try and eliminate them, as they often trigger autoimmune disease activity when they go awry. T cells and B cells are lymphocytes, which are a type of white blood cell. As per the National Human Genome Research Institute, B cells produce antibodies that target invading bacteria, viruses and toxins, whilst T cells destroy the body’s own cells that have become infected, or have turned cancerous.

There has been some fascinating research into T cells and B cells, although they are still in the preclinical stages. According to Taylor et al. (2023):

“One such therapy is redirecting T cells to selectively kill anti-β2GPI antibody-producing B cells using chimeric autoantigen-TCRs (CATCRs), allowing T cells to bind autoantigen-specific B-cell receptors (BCRs) and induce selective cell death. Other B-cell therapies include monoclonal antibodies to B-cell activating factor (BAFF), which has been shown to exist at higher levels in many types of autoimmune diseases, including APS.”

In brief, T cells and B cells go hand in hand in the body, and targeting one will affect the other for better or for worse. Within the thymus gland, B cells play an active role in ‘training’ T cells on which cells to attack, and which to leave alone.

According to Afzali et al. (2024) in this latest research paper:

“CD40-induced B cell antigens, which, besides AQP4, comprise additional potentially disease-relevant autoantigens such as Anxa2, App and Cpd. Autoantibodies to ANXA2 and APP are associated with antiphospholipid syndrome and cerebral amyloid angiopathy-related inflammation.”

Thus, perhaps future treatments for Antiphospholipid Syndrome might target B cells and T cells more specifically, by ‘switching off’ the bad stuff whilst leaving the good alone.

Disruption of Neutrophilic Involvement in Antiphospholipid Syndrome

According to Papayannopoulos (2018), “Neutrophils are the most abundant innate immune effector cells of the human immune system”, and come with antimicrobials on a broad spectrum. Neutrophil extracellular traps (NETs) are a combination of chromatin fibres, DNA and histones, and they play an important role in immobilising and killing invasive microorganisms, thereby protecting against infection.

However, NETS are also sources of autoantigens and immunostimulatory proteins, and can stimulate autoimmune diseases such as Lupus (SLE), vasculitis and psoriasis (Kaplan and Radic, 2012). Apart from that, NETs play a role in blood coagulation both through platelet and coagulation cascade activation, and can contribute to the formation of both arterial and venous blood clots (Kmeťová et al., 2023).

Clinical trials in Primary Antiphospholipid Syndrome patients with no comorbidities have also shown that these individuals had high levels of anti-NET antibodies, which can potentially trigger the complement cascade (Zuo et al., 2023). Another study found that APS patients with a high risk of thrombosis had more NETs and activated protein C resistance (Foret et al., 2022).

With NETs being drivers of thromboinflammation in APS, research into disruption of this pathway is underway. Two FDA-approved medications with antineutrophilic properties are being studied, as well as selective modulation of immune cell activity. This could potentially result in neutralisation of adhesive properties of cells, thus reducing thrombosis in both arterial and venous vascular beds (Taylor et al., 2023).

Beta-2-Glycoprotein I (β2GPI) & Future Therapeutic Research in Relation to APS

There are only three proteins in the body that are able to up and down regulate the complement and coagulation systems, namely: C-reactive protein (CRP), thrombomodulin and Beta-2-Glycoprotein I (β2GPI). β2GPI is a unique five domain protein, and exists in open (J-shaped), S-twisted, and closed (O-shaped) conformations (McDonnell et al., 2020), and according to Ağar et al. (2010):

“In contrast to the circular conformation, the open fishhook-like conformation of β2GPI has a profound effect on the aPTT. Therefore, we propose that the conformation of β2GPI in plasma is predominantly circular.”

Coagulation from β2GPI is dependent on the surrounding environment, and can have an anticoagulant, antiplatelet and procoagulant effect (McDonnell et al., 2020). β2GPI is also known to bind to phospholipids and DNA, where interactions with DNA further extend to NETs (which we touched on previously) (Kmeťová et al., 2023).

According to McDonnell et al. (2020):

“These actions of β2GPI can be influenced by aβ2GPI antibodies present in patients with APS and may be potential therapeutic targets. Assays to measure levels of antibodies to β2GPI and to DI show promise in improving diagnosis and risk stratification of patients with APS. A number of proposed therapeutic agents that target β2GPI/aβ2GPI interactions are in development.”

In basic terms, what this means is that β2GPI has implications in coagulation and Antiphospholipid Syndrome. Future therapies may target the blocking of these interactions, in order to reduce the cascade of thrombosis.

One of these new potential therapeutics is A1-A1, which is a peptide that targets the fifth domain of β2GPI, in order to prevent binding to cell surfaces. Another potential therapeutic is TIFI, a cytomegalovirus capsid peptide, which also targets the fifth domain of β2GPI, and might be able to inhibit the thrombotic effects of IgG antibodies.

1N11 is a monoclonal antibody that has also been shown to target ß2GP1 to decrease binding of antiphospholipid antibodies (aPLs) to proteins. Recombinant domain I molecule is also able to bind to aPLs, which in turn prevents their adverse effects. Researchers are still trying to understand the full role of β2GPI as well as Antiphospholipid Syndrome. So whilst these therapeutics sound exciting, it will probably still be many years before we see them in practice (McDonnell et al., 2020; Fierro et al., 2022).

Aptamers / Next-Generation Thrombin Inhibitor Consisting of DNA Molecules

Finally, let’s take a look at aptamers. Aptamers are single-stranded oligonucleotides (DNA or RNA molecules) that are capable of binding to proteins or other cellular targets with great specificity (Arbuthnot, 2015; Ni et al., 2011). They are small in size, non-immunogenic, and there are different kinds that show promise in a variety of immune related treatments – from antibiotic alternatives, to autoimmune diseases such as Sjögren’s disease, to suppression of tumour growth. The good news is that many of these therapeutic aptamers are in the mid to late stage of clinical trials, and might be ready within 5 – 10 years (Yasmeen et al., 2020).

In relation to Antiphospholipid Syndrome and its potential complications, a new DNA drug to fight blood clots has been discovered. Heparin is used as an anticoagulation drug in APS patients during emergencies, but up to 3% of patients who are on heparin for various medical reasons develop heparin-induced thrombocytopenia (HIT), which causes the blood to clot instead. HIT is a life-threatening complication where platelet counts drop, and the patient is at risk of thrombosis. The medications used to treat HIT – argatroban and bivalirudin – have no antidotes.

Recently it has been found that the anti-thrombin DNA aptamer, M08s-1, might act as a promising antidote for HIT. It also does not cross over into the placenta of pregnant women. According to Nagano et al. (2023):

“The dimerized M08s-1-based aptamers had about 100-fold increased binding affinity to human and mouse thrombin compared with the monomer counterparts.”

Discovery of 2 Missing Enzymes in People with Antiphospholipid Syndrome

According to NaveenKumar et al. (2024):

“Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.”

Goodwin from Michigan Medicine explains this unexpected research finding in simpler terms here. In brief, the enzymes CD39 and CD73 which normally work together to cool down inflammatory molecules known as adenosine triphosphate were not found in patients with APS. This results in instigation of cells like neutrophils and platelets that contribute to the blood coagulation cascade.

NaveenKumar et al. (2024) has also discovered that the receptors P2X7 and P2Y2, which play a role in platelets and neutrophils respectively, are key components in the inflammatory response from the accumulated adenosine triphosphate. Blocking these receptors on cells related to Antiphospholipid Syndrome returned them to a healthy state.

Research such as this matters so much even if there is little funding for research into Antiphospholipid Syndrome specifically. Every bit of knowledge helps medicine to advance as a whole.

Conclusion to the Latest Research on Antiphospholipid Syndrome

Currently the main form of APS management and treatment is with the use of blood thinning medications, which come their own sets of problems. So it’s interesting to see that the future direction of APS treatment delves quite a bit into more targeted therapies on a biological level.

I hope that this peek into the latest research on Antiphospholipid Syndrome has granted you some insight and hope into the possibilities of more effective APS diagnosis, prevention and treatments on the horizon. Perhaps some day, these fantastic researchers and doctors will find a cure as well. For now, take good care of yourself, and keep an eye out for the A – Z Antiphospholipid Syndrome guide to be released soon!

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References:

1. Afzali, A. M., Nirschl, L., Sie, C., Pfaller, M., Ulianov, O., Hassler, T., … & Korn, T. (2024). B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4. Nature, 627, 407-415. https://doi.org/10.1038/s41586-024-07079-8
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