John Stewart Cameron

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.

Recombinant human erythropoietin shortens the uraemic bleeding time without causing intravascular haemostatic activation

Blood rheology and haemostasis have been investigated in 8 haemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). The aim was to elucidate the mechanism by which rHuEPO improves haemostasis, and to determine whether rHuEPO promotes intravascular coagulation. Investigations were performed before, and after 3 months of treatment. Haemoglobin and haematocrit rose significantly after rHuEPO (p less than 0.001) and there was a concurrent shortening of the bleeding time. No significant changes were observed in platelet aggregation, thromboxane generation, or platelet nucleotide content during the treatment period. Whole blood viscosity increased following rHuEPO (p less than 0.01), but plasma viscosity and red cell deformability were unchanged, as were markers of intravascular platelet activation and plasma levels of cross-linked fibrin derivatives. No patient suffered from thrombosis during the study period, and elevation of the haematocrit in uraemic patients up to 0.35 with rHuEPO did not appear to lead to intravascular coagulation. Shortening of the prolonged bleeding time in haemodialyzed patients following rHuEPO appeared to be due to the increase in circulating red cells, rather than to changes in platelet reactivity.

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.

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.

The pathogenesis of glomerulonephritis

SummaryProgress has been made in understanding glomerulonephritis but the answers to many key questions still elude us. It appears that glomerular damage arises from immune events which result from an interaction between a susceptible individual and some environmental agents, usually an infection. In the developed world the role of the genetic constitution is predominant, whilst in the Third world the overwhelming exposure to pathogens may be crucial. Immune complex formation undoubtedly plays a major role in the initiation of glomerular injury, but deposition of soluble preformed complexes within the glomerulus now seems to be only one mechanism,in situ combination of fixed antigen and free antibody, and insoluble (precipitating) complexes both playing a part as well. New understanding of modes of damage to the glomerulus strongly implicates monocytes as injurious agents in both experimental and human nephritis, and platelets may also play a role in amplifying injury. One of the main questions is why only some forms of glomerulonephritis in only some patients progress to renal failure. Whilst continuing exposure to the antigen initiating the nephritis may be important, secondary mechanisms involving autologous antigens may be important. Further, non-immunologic mechanisms which arise from hyperperfusion of glomerular capillaries appear capable of damaging the glomerulus, and both this mechanism and proteinuria itself appear capable of inducing glomerulosclerosis. The role these non-immunologic mechanisms play may be the reason for our failure, in general, to influence the course of glomerulonephritis by manoeuvres designed to inhibit immunologic injury.