Immunological abnormalities in glomerulonephritides

Abstract

Immune complex deposition in glomeruli is believed to cause many forms of human glomerulonephritis (gn). One as yet unproven hypothesis suggests that relative immune deficiency prevents antigen elimination, thereby predisposing to immune complex formation and deposition. We sought in the present study to identify in such patients defective immune function. Forty-four sequential patients were studied who satisfied the following criteria: (1) serum creatinine levels ≤ 0.2mM/L, (2) renal biopsy which allowed unequivocal histological classification and in which immune deposits were demonstrated by immunofluorescence or electron microscopy. (3) not receiving corticosteroids or immunosuppressives. We were able to demonstrate in patients with gn, compared with age and sex-matched normal controls, an increased incidence of immunological changes which included: <ul><li>1.Elevated serum levels of several immunoglobulin classes in various forms of gn: a novel finding was of raised IgM in 4 of 9 patients with focal sclerosing gn and glomerular IgM deposition.</li><li>2.Patients with all forms of glomerulonephritis showed significant reduction in antibody response to tetanus toxoid compared with controls in their mean rise in litre (P < 0.05) and in numbers failing to respond (P < 0.01).</li><li>3.Increase in total haemolytic complement (CH₅₀), and C-reactive protein, suggesting an acute phase inflammatory response. Isolated defects in functional C₂ were detected in 4/37 patients, but their disease was in no way unique.</li><li>4.No impairment in T cell function as measured by delayed hypersensitivity skin tests or DNCB sensitization. However, 8 patients (20%) had a reduced response to PHA stimulation, of whom only one (a patient with tuberculosis) had an inhibitory serum factor.</li></ul> Since uraemia and debility cannot be invoked to explain these findings, we suggest that they indicate immunological activity which may be important in genesis of the glomerular damage.