Fat-targeting Autoantibodies Linked to Increased Risk of Blood Clots, Miscarriage in Scleroderma Patients

Autoantibodies against fat molecules present in the membrane of cells, called antiphospholipid antibodies, are associated with an increased risk of blood clots and miscarriage among scleroderma (SSc) patients, a study reports.

The study, “Prevalence and Clinical Associations of Antiphospholipid Antibodies in Systemic Sclerosis: New Data From a French Cross-Sectional Study, Systematic Review, and Meta-Analysis” was published in the journal Frontiers in Immunology.

A hallmark of SSc is the production of autoantibodies, which react against the body’s own tissues, including targeting nucleic acids or DNA/RNA-binding proteins, detected in more than 95% of patients.

The presence of certain autoantibodies has been linked with lesions in blood vessels (vasculopathy) and the risk of thrombosis.

Patients with antiphospholipid syndrome (APS), also known as Hughes syndrome, a disorder of the immune system, have an increased risk of blood clots because of the presence of autoantibodies against fat molecules (phospholipids) present in the membrane of cells, which makes the blood more likely to clot.

These antiphospholipid antibodies (aPL) include several antibody types — lupus anticoagulant, anticardiolipin antibody, or anti-b2 glycoprotein-I antibody (anti-b2GpI) — and previous studies have found that they may also be present in the blood of patients with SSc (presence varying from zero to 57 percent of cases).

Because these antibodies may increase the likelihood for blood clots, a group of researchers  assessed their prevalence in the blood of 249 SSc patients, most of them women (82 percent) with limited cutaneous SSc. Eighteen percent had a history of thrombosis (blood clots), and 21 percent had had a miscarriage.

The team tested the patients for the lupus anticoagulant, anticardiolipin, and anti-b 2GpI antibodies.

Results showed that 16 patients were positive for one or more of the aPL antibodies, with an overall prevalence of 6.4 percent. In these patients, the more prevalent aPL antibody was anti-b2GpI, which was detected in 68.8 percent, followed by lupus anticoagulant (25 percent), and anticardiolipin antibody (18.8 percent).

Researchers observed that the presence of aPL antibodies was significantly linked to a higher risk of blood clots (thrombus) within a vein (6.25 times higher risk) and miscarriage (5.43 times higher risk).

To have an idea of the worldwide prevalence of aPLs in SSc patients, researchers performed a systematic review analysis of published studies on SSc and aPL included in two databases, PubMed and Embase. Out of an initial pool of 1,291 studies, they analyzed 24 studies that included a total of 3,036 adult SSc patients.

The analysis revealed a marked variation in the prevalence of aPL, from 9% to 20% (overall prevalence of 14%), which may be linked to the heterogeneity of the studies and their different geographical locations, which is linked to potential differences in genetic and/or environmental factors.

The overall pooled prevalence of the lupus anticoagulant antibodies was 1%, and anticardiolipin and anti-b2GpI antibodies 9% each.

Overall, “this study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8–10.4) and an overall worldwide pooled prevalence of 14% (9–20),” researchers stated.

Based on the results, the team concluded that in the SSc cohort analyzed, “aPL positivity was associated with [venous thrombosis] and miscarriage.”