C A Bowman

Clinical and pathological data on 71 patients from throughout the British Isles who developed antiglomerular basement membrane antibody mediated nephritis in the period 1980-4 were studied. Two principle patterns of disease were recognised: young men presenting in their 20s with Goodpasture's syndrome (glomerulonephritis and lung haemorrhage) and women presenting in their 60s with glomerulonephritis alone. The effect of treatment on prognosis of a total of 108 patients was also reviewed (the 71 patients plus patients seen before 1980 at Hammersmith Hospital). Treatment with prednisolone, cytotoxic drugs, and plasma exchange hastened the time to clearance of autoantibody and improved the outlook of patients who were not dependent on dialysis and those with lung haemorrhage.

A patient who presented with bilateral adhesive capsulitis of the shoulder, oligoarthropathy and rapidly progressive proximal myopathy is described. Although clinically euthyroid, autoimmune and biochemical hypothyroidism was the only predisposing factor found. Clinical deterioration after initiation of thyroxine replacement was followed by delayed improvement with reduction in initially elevated ESR and CRP.

Repeated low-dose injections of mercuric chloride (HgCl2) in the brown Norway (BN) rat result in polyclonal activation which includes the induction of anti-glomerular basement membrane (GBM) autoantibodies. We examined the kinetics of various autoantibodies produced in vivo, general features of polyclonal activation such as total IgG levels and immune complex formation, and the relationship between organ specific autoimmunity and tissue injury in the kidney and thyroid. The production of immune complexes and autoantibodies to GBM and thyroglobulin was short lived, and the increase in levels of total IgG and antibodies to ssDNA and dsDNA was prolonged; the antibody response to collagen types I and II was intermediate in duration. Autoantibodies induced by HgCl2 caused only mild and variable tissue injury in the kidneys and did not induce abnormalities in the thyroid. These studies demonstrate that immunostimulation by mercury may result in the formation of a range of autoantibodies, with variable kinetics and pathogenicity.

To study the possible relationship between individual subclass expression and pathogenesis of antibody-mediated disease, we examined the immunoglobulin-G subclass of antiglomerular basement membrane (GBM) antibodies, in the sera of 20 patients with auto-antibody mediated nephritis, as well as in a limited number of kidney eluates, using a solid phase radioimmunoassay and monoclonal antibodies specific for human IgG subclasses. Only anti-GBM antibodies of the IgG1 and/or IgG4 subclass were detectable, both in the circulation and in renal eluates. Recurrence of circulating anti-GBM antibody during convalescence occurred in two patients out of 49 studied sequentially for more than 12 months. In both cases only antibodies of a single subclass were involved. The recurrence of IgG1 antibody (which can fix complement and bind macrophages) was associated with clinical manifestations of disease, whereas the reappearance of IgG4 antibody (which cannot engage amplifiers of the inflammatory response) did not appear to be harmful. Thus, in anti-GBM auto-antibody mediated nephritis, clear restriction in the subclass of IgG auto-antibody occurs, and this may be important in disease expression.

We describe a sensitive radio-immunoassay for auto-antibodies to glomerular basement membrane (GBM). The assay discriminates patients with glomerulonephritis associated with circulating auto-antibodies to glomerular basement membrane from those with other forms of nephritis. Monitoring of antibody levels in sequential serial serum samples enables drug therapy to be tailored precisely to control the aberrant immune response, a situation unique in the management of glomerulonephritis.