AUTOANTIBODIES AGAINST C1Q: VIEW ON ASSOCIATION BETWEEN SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE MANIFESTATION AND C1Q-AUTOANTIBODIES

Background: Activation of the complement system is the first step in the prevention of damage by immune complexes. Systemic lupus erythematosus 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.Objectives: We studied 42 patients (38 female and 4 male, aged 19-64) with systemic lupus erythematosus. Twenty eight of them have proven with renal biopsy lupus nephritis, 14 of patients have evidence for lupus pneumonitis and 11 - for central nervous system involvement.Methods: All patients were tested for both basic and subclass ELISAs for C1qAb using modification of the methods of JJ Wisnieski and SM Jones. Whole C1q was purified from human plasma by the method of AJ Tenner, PH Lesarve and NR Cooper.Results: Raised C1qAb titres were found in 18 of patients (42,86%). Among all patients with C1qAb 12 had renal manifestation of SLE (83,33% of them had focal or diffuse proliferative glomeruloneph ritis), 6 - central nervous system involvement and 5 - lupus pneumonitis. Patients with raised C1qAb titres were younger,7 of them were positive for antibodies to dsDNA. The magnitude of proteinuria was positively associated with the presence of C1qAb. In 7 of our patients was established selective complete C1q deficiency, in two of them there were clinical data for presence of systemic lupus erythematosus in the family.Available sera testing positive for IgGC1qAb were analyzed for C1qAbIgG subclass distribution. Six patients had IgG2C1qAb only, 3 patients - IgG1C1qAb only, and 9 had both IgG1 - and IgG2C1qAb. Therefore, IgG2C1qAb was present in 83,33% of patients. The subset of sera from patients with IgG1- or IgG2C1qAb were 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 G1/G2 (3,4 ± 2,1) was similar to that reported in the literature for disease free individuals. The percentage of IgG2C1q relative to total IgG2 was significantly greater than percentage of IgG1C1qAb relative to total IgG1 (0,03 ± 0,06% vs. 0,01 ± 0,02% respectively, P<0,005, t-test).Conclusion: In our patient population the IgG2 component of the autoantibody response to C1q is disproportionately enriched relative to the overall IgG subclasses distribution, as no alteration in IgG subclass distribution was noted. The C1qAb in our population were predominantly of IgG2 and IgG1 subclasses. The mechanisms mediating autoantibody pathogenicity remain unclear. It has been proposed that C1qAb may act systemically by up-regulating activation of classical complement pathway. 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, but significance of C1qAb for lupus pneumonitis and cerebrovasculitis is target to future investigations.Citation: , volume , supplement , year 2002, page Session: SLE – Clinical aspects 1