Geoffrey Frampton

Severe Guillain-Barré syndrome: An association with IgA anti-cardiolipin antibody in a series of 92 patients

To determine whether anti-cardiolipin antibodies (ACA) are associated with acute Guillain-Barré syndrome (GBS), we studied sera from 92 patients with GBS, 82 age- and sex-matched hospital controls and 24 patients with uncomplicated cytomegalovirus or Campylobacter jejuni infection, using an isotype-specific ACA enzyme-linked immunosorbent assay (ELISA). IgA ACA titres (but not IgG ACA or IgM ACA) were significantly elevated (P = 0.002) in GBS patients compared to controls, and associated with peak disease severity (P = 0.01), but not initial or residual disability, nor duration of neuropathy. Abnormal IgG ACA may cause or result from myelin damage in GBS.

Synthesis of thromboxane B2 in uraemia and the effects of dialysis

The generation of thromboxane B2 (TxB2) from its natural precursor, arachidonic acid, was studied in vitro in order to assess further the prostaglandin pathway in the platelets of patients with chronic renal failure. Some, but not all patients with conservatively treated uraemia synthesised significantly less TxB2 then controls and the same patients were also hypo-aggregable to arachidonic acid. The synthesis of TxB2 appeared normal in a group of patients on chronic ambulatory peritoneal dialysis (CAPD). In contrast, a group of patients on long-term maintenance haemodialysis produced significantly greater amounts of TxB2 and were hyper-aggregable to arachidonic acid, a finding which may be relevant to the high incidence of atherosclerosis and vascular disease in these patients.

Pathogenetic Aspects of Autoantibodies to Endothelial Cells in Systemic Vasculitis

The vascular endothelium is no longer considered to be little more than a passive, semipermeable, thrombo-resistant membrane which lines blood vessels. It is now clearly apparent because of the major advances in endothelial cell culture techniques (1) that the endothelium constitutes a dynamic interface between the blood and the rest of the body. Autoantibodies that recognise antigens on endothelial cells (AECA) have been described in many disorders with obvious vascular pathology (2–7). AECA have been detected by their ability to bind to cultured human umbilical vein endothelial cells (HUVEC) growing on plastic ELISA plates, or detected using functional assays, in which the end point is monocyte, neutrophil, or complement-dependent cytolysis. Recently, several groups (8–10), including are own (11), have reported the presence of AECA in ANCA positive Wegener’s granulomatosis (WG) and microscopic polyarteritis (MPA). However, little is known of the target autoantigens in systemic vasculitis or whether these antibodies are of pathogenetic significance. Therefore the aim of this study was to determine in more detail the relationship between AECA, ANCA and disease activity in patients with WG or MPA.

Platelet‐associated IgG in idiopathic glomerulonephritis and the nephritis of systemic lupus erythematosus

Summary We studied platelet‐associated IgG (PAIgG) in patients with the nephritis of systemic lupus erythematosus (SLE) and with idiopathic glomerulonephritis (IGN), and found no increase in PAIgG in the patients with IGN, and an increase in only a minority of patients with SLE, all of whom had active disease. Patients with IGN and a nephrotic syndrome had both a low serum IgG and a low PAIgG. The increase in PAlgG in the patients with SLE correlated with the titres of antibody against dsDNA in the serum, but not with the platelet‐agglutinating immune complexes also present. Intraplatelet serotonin, however, was reduced in both groups, and this correlated with the amounts of platelet‐agglutinating complexes in the serum of the SLE patients. Immune complexes may associate with platelets in vivo to cause this release, but if so this must be a reversible phenomenon (‘hit and run’immune platelet injury); alternatively, the Fc binding to the platelet surface may be weak and insufficient to survive the ex vivo washing procedures.