Antiphospholipid (Hughes) syndrome 40th anniversary

Abstract

This article is a celebration of the 40th anniversary of APS, a disease that appears to affect one in 2000 people. The quality of life of patients affected has improved significantly as a result of early diagnosis and effective treatment.

Scores of new diseases were described during the twentieth century, but two diseases, human immunodeficiency virus (HIV) and antiphospholipid syndrome (APS), dominated the eighties and nineties involving several medical specialities including obstetrics. HIV occurred during the era of modern virology and was characterised very speedily and effective treatment followed during the last decade of the 20th century.

The evolution of APS is interesting. In 1957, Laurell and Nilsson found an (lupus) anticoagulant with antithromboplastin effect in two patients who had hypergammaglobulinemia and haemorrhagic diathesis and whose sera gave false positive biologic reactions for syphilis. ¹ Twenty six years later, a research team from the Hammersmith Hospital in west London lead by GRV Hughes reported in the British Medical Journal (BMJ) that the lupus anticoagulant (LA) was a useful marker in a subset of patients with systemic lupus erythematosus (SLE) and other connective tissue disorders at risk for the development of thromboembolic complications. ² In the same issue (8 October 1983), the same team also reported in another article that five out of six patients with SLE and unexplained pulmonary hypertension had the LA in their sera. ³ A week later, in an editorial in the BMJ, Hughes commented that in some patients, three apparently unrelated clinical features of SLE – recurrent venous thrombosis, central nervous system disease (including myelitis) and recurrent abortions – had common pathogenic mechanisms, and the serological abnormality common to some (but not all) of these patients was a circulating anticardiolipin antibody responsible for the positive Wassermann reaction (or false positive serological test for syphilis). ⁴ A month later, Hughes’ team reported their new solid-phase radioimmunoassay for the detection of anticardiolipin antibodies which was 200-400 times more sensitive than the precipitation method used in the Venereal Disease Reference Laboratory (VDRL) test in the Lancet (26 November 1983). ⁵ Sixty one per cent of serum samples from patients with SLE had high levels of anticardiolipin antibodies of at least one immunoglobulin class. They found strong correlations between raised anticardiolipin levels and the LA, venous and arterial thrombosis, pulmonary hypertension, multiple abortions and thrombocytopenia. This immunoassay appeared to have predictive value for thrombosis in SLE and related immune-related disorders. A new disease, antiphospholipid syndrome was characterised. This year, 2023, marks the 40th anniversary of its description. The antiphospholipid antibodies include lupus anticoagulant, moderate to high titre anticardiolipin, or anti-β2GPI antibodies of IgG or IgM isoforms.

In 1994, at the 6th International Antiphospholipid Conference in Louvain, APS was given the name Hughes syndrome in recognition of 20 years of research by Hughes and his team.

APS is an immune-mediated thrombo-vascular disease driven by antiphospholipid antibodies binding with phospholipids and phospholipid-binding proteins on cell surfaces causing thrombotic events, obstetric morbidity and various other clinical features and complications, some non-thrombotic, affecting various parts and organs of the body. Hence, patients may present to almost every medical speciality. It is associated with significant morbidity and is the cause of 13.5% of patients with strokes, 11% of myocardial infarction, 9.5% of deep vein thrombosis and 6% of all pregnancy morbidity. ⁶ Affected patients tend to be young; seven out of eight patients are under the age of 50 years. ⁷

Early diagnosis is important. The main treatment of APS is the use of vitamin K antagonists, but there are other emerging therapies. ⁸

This article is a celebration of the 40th anniversary of APS, a disease that appears to affect one in 2000 people. The quality of life of patients affected has improved significantly as a result of early diagnosis and effective treatment.

Professor Graham Hughes continues to do charitable work promoting education of patients and medical staff on lupus and APS nationally and internationally. We send Professor Hughes our warmest wishes for good health.