Graham Hughes1 and Shirish Sangle2
(1)
The London Lupus Centre, London Bridge Hospital, London, UK
(2)
Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK
Abstract
For me it started in Hammersmith and took off in Jamaica. In Hammersmith Hospital, our lupus team had a particular interest in brain involvement, and between 1971 and 1975, we published papers on antibodies which appeared to cross-react with the brain.
1.1 The Discovery
For me it started in Hammersmith and took off in Jamaica. In Hammersmith Hospital, our lupus team had a particular interest in brain involvement, and between 1971 and 1975, we published papers on antibodies which appeared to cross-react with the brain.
In 1975, I was posted “on loan” to the University of the West Indies to set up a rheumatology department in the hospital there. With me was a technician, Geoff Frampton, and a clinical research fellow, Wendell Wilson, a Guyanese doctor who stayed on after my year there to run the new unit.
We saw a lot of lupus and soon became intrigued with a group of young women who developed a form of spinal paralysis.1 Interestingly, these patients had, in common, a positive lupus (ANA) test and a “false positive” test for syphilis, a finding also sometimes seen in lupus. We began to consider (possibly wrongly) the possibility that these “syphilis” antibodies (anticardiolipin) might cross-react with brain and cord phospholipids such as cephalin and sphingomyelin.
On my return to London we set up assays for anticardiolipin antibodies and studied our rapidly growing lupus population at Hammersmith Hospital.
It quickly became clear that our patients with anticardiolipin antibodies (aCL) had a number of important clinical characteristics.
Firstly, they had a propensity to clot – not just veins, but also, critically, arteries. The clinical picture, filled in on our clinic meetings and ward rounds, included recurrent miscarriage, strokes, memory loss, headaches, labile hypertension, livedo, Budd-Chiari, renal vein thrombosis, occasional thrombocytopenia, chorea, pulmonary hypertension and, rarely, catastrophic widespread thrombosis. We realised that the syndrome was not confined to lupus, but could – and frequently did – occur in isolation.
In 1982, I presented the syndrome to the Heberden Society of the British Society for Rheumatology, and in 1983, our first papers in the BMJ and Lancet were published. We initially called it the “anti-cardiolipin syndrome”, but at the 1984 meeting of the British Society of Rheumatology, changed the name to “Primary Antiphospholipid Syndrome” (APS).
1.2 The Background
Some of the individual strands of what has become “the Antiphospholipid Syndrome (APS)” are to be found in the history of lupus. It is possible that one of the first case reports came from the great William Osler, who reported a male lupus physician with a stroke.
In 1906, Wasserman described the “reagin” reaction, one of the earliest autoantibody studies. In the 1960s and 1970s, the so-called lupus anticoagulant (LA) became widely studied, with cases of lupus patients reported with LA and abortion, as well as LA and thrombosis.
In the 1990s, it was found that the antibodies reacted not with simple phospholipids, but with a complex of altered phospholipids and so-called phospholipid-binding proteins such as Beta 2 glycoprotein and prothrombin.
Since 1983, the story has gained momentum, with a growing literature, with biennial international conferences and with inter-laboratory quality control studies.
Most of all, the syndrome is now recognised as a major cause of (young) strokes, of (mainly young) heart attacks, of migraine, of memory loss – and, of course, of thrombosis.
In the following chapters, I will briefly describe the effects of the syndrome on different organs.
Footnotes
1
A number of these cases had “Jamaican neuropathy”, a disease now known to be caused by a retrovirus.