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Ativation of the complement system is the first step in the prevention of damage by immune complexes. Systemic lupus erythematosus (SLE) is the prototype of immune complex diseases. The classical pathway of the complement system is considered to be the most important pathway in immune complex clearance. This pathway may be activated by IgM- and IgG-containing immune complexes after binding to C1q.1
In 1984 autoantibodies to C1q (C1qAb) were reported to be present in serum of patients with SLE.2 The recognition that C1q may serve as a non-organ-specific autoantigen has attracted a growing number of investigators.3
We studied 42 patients (38 female, four male, aged 19–64) with SLE. Twenty eight (67%) had proven renal biopsy lupus nephritis (two patients had WHO class II lesions, four had WHO class III, 18 had WHO class IV, four had WHO class V), 14 (33%) patients had evidence of lupus pneumonitis, and 11 (26%) central nervous system disease (table 1).
All patients were tested by both basic and subclass enzyme linked immunosorbent assays (ELISAs) for C1qAb using a modification of the method of Wisnieski and Jones.4 Whole C1q was purified from human plasma by the method of Tenner et al.5 Raised C1qAb titres were found in 18 (43%) patients. Of the patients with C1qAb, 12 had renal manifestations of SLE (10 (83%) of them had focal or diffuse proliferative glomerulonephritis), six central nervous system disease, and five lupus pneumonitis. Patients with raised C1qAb titres were younger, seven of them were positive for antibodies to dsDNA. The magnitude of proteinuria was positively associated with the presence of C1qAb.
Selective complete C1q deficiency was established in seven of our patients (Nos 6, 11, 16, 18, 28, 32, 33); in two of them (Nos 18, 28), clinical data showed the presence of SLE in the family.
Available serum samples testing positive for IgG C1qAb were analysed for C1qAb IgG subclass distribution. Six (33%) of the 18 patients had IgG2 C1qAb only, 3/18 (17%) patients had IgG1 C1qAb only, and 9/18 (50%) had both IgG1 and IgG2 C1qAb. Therefore, IgG2 C1qAb was present in 15/18 (83%) patients. The subset of sera from patients with IgG1 or IgG2 C1qAb was assayed for total serum IgG1 and IgG2 levels by radial immunodiffusion. The mean total serum IgG1 was 7.9 (4.5) mg/ml, the mean total serum IgG2 was 2.6 (1.4) mg/ml. The mean ratio of IgG1/IgG2 (3.4 (2.1)) was similar to that reported in the literature for disease free subjects.6 The percentage of IgG2 C1qAb relative to total IgG2 was significantly greater than the percentage of IgG1 C1qAb relative to total IgG1 (0.03 (0.06)% v 0.01 (0.02)% respectively, p<0.005, t test). Thus in our patient group the IgG2 component of the autoantibody response to C1q was disproportionately enriched relative to the overall IgG subclasses distribution, as no alteration in IgG subclass distribution was noted. The C1qAb in our group were predominantly of IgG2 and IgG1 subclasses. This distribution is consistent with that found by Wisnieski and Jones in a study characterising C1qAb in patients with SLE and hypocomplementaemic urticarial vasculitis,4 but contrasts with the IgG3 and IgG2 predominance reported by Coremans et al in patients with SLE.7
The mechanisms mediating autoantibody pathogenicity remain unclear. It has been proposed that C1qAb may act systemically by up regulating activation of classical complement pathway.8 Alternatively, C1qAb may act locally within the renal glomerulus to enhance tissue injury initiated by immune complex deposition. The association of C1qAb with proliferative lupus nephritis is now well established,2 but the significance of C1qAb for lupus pneumonitis and cerebrovasculitis should be a target for future investigations.
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