Histopathological criteria were used to classify twenty-four patients with chronic urticaria into three groups, which were then studied to establish whether circulating immune complexes (CICs), complement activation and deposition of immunoreactants are confined to patients with urticarial vasculitis. Group I (three patients) had classical urticarial vasculitis, and two of these patients showed hypocomplementaemia with evidence of C3 conversion and deposition of immunoreactants in lesional and uninvolved skin. Ten patients (group 2) with a dense perivascular mixed-cellular infiltrate had normal or raised complement levels and infrequent evidence of C3 conversion. Immunoreactants were detected only in their lesional skin. Eleven patients (group 3) had only a sparse perivascular infiltrate. In this group, complement was normal and immunofluorescence was essentially negative. Cryoglobulins were detected in group I patients only. Monoclonal rheumatoid factor and C1q binding were positive in all group I patients, half the group 2 patients and none of the group 3 patients. This study suggests that urticaria and urticarial vasculitis form a disease continuum, and identifies a group of patients with features intermediate between urticarial vasculitis and ordinary urticaria.
SUMMARYGlomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have Investigated the involvement of tumour necrosis factor-alpha (TNF-a), IL-la and IL-l^in this phenomenon by passive immunization against these cytokines. Anti-TNF-«oranti-IL-l/i antibodies given 15 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria. the prevalence of giomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Aibuminuria in anti-GBM Ab alone was U ±3. LPS/anU-GBM Ab 87 + 22. and anti-TNF-a antibodies/LPS/anti-GBM Ab 21 ±6 mg/24 h (mean + s.e.) /*<0-05. Passiveimmunization with antibodies to IL-l/f had a similar effect (anti-GBM Ab.O-6 + 0-l,LPS/anti-GBM Ab.92+19.anti-IL-l/fantibodies/LPS./anti-GBM Ab39±8mg/24h. P<{)QS). The prevalence of glomerular capillary thrombi was also reduced significantly by these Ircatmcnts; from 22±5% to 4±1% in the case of anti-TNF-a antibodies and 28±5% to 13 ±4% with anti-IL-1 ^antibodies, Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42 + 3 to 25±1 In the case of anti-TNF-D; and 47±2 to 30+1 with anti-IL-lâ ntibodies. In eontrast, passive immunization againsi IL-la had no effect on either albumin excretion {4 + 3, 83 + 22 and 77 + 24 mg/24 h), glomerular capillary thrombi (2+1; I9±5 and !6±3) or glomerular neutrophil infiltrate (22 + 3; 47 + 5 and 48 + 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-a and \L-\(i but not by IL-la.Keywords nephrotoxic antibody lipopolysaccharide tumour necrosis factor-alpha interleukin-1 a and P aipha 2-macroglobulln
The mechanisms by which intercurrent bacterial infections are associated with increased tissue injury in some forms of glomerulonephritis may include complement activation by bacteria and subsequent increased glomerular neutrophil (PMN) infiltration. We have studied the effect of complement activation after cobra venom factor (CVF) in anti-glomerular basement membrane (GBM) antibody-mediated disease. A single injection of CVF 24 h before the administration of heterologous nephrotoxic globulin (NTG) to Sprague-Dawley rats resulted in greatly increased albuminuria in some animals on the second day of this model. This phenomenon was reproducible and depended on the presence of circulating PMN and complement. We have previously shown that the administration of CVF on days 9 and 11 of the HgCl2 model in inbred Brown Norway rats, resulted in increased albuminuria in all animals at day 17 (p < 0.05). The administration of small amounts of CVF with consequent complement activation in antibody-mediated disease represents a model for the increased injury seen after infection in human disease.
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