P0185ROLE OF THE COMPLEMENT SYSTEM IN PROLIFERATIVE LUPUS NEPHRITIS

Abstract

Abstract Background and Aims Lupus Nephritis (LN) is a serious complication in patients with Systemic Lupus Erythematosus (SLE) which confers a worse prognosis in patients that develop this condition. It is well known that histological lesions correlate poorly with the prognosis of the disease, but little is known about the role of complement proteins deposition in kidney tissue. The aim of this study was to evaluate the effect on renal manifestations of the deposition in renal tissue of C3, as a marker of alternative pathway, C4 as a marker of the classical pathway and C1q representing the lectin pathway. Method A retrospective observational study was performed, including native kidney biopsies with a diagnosis of lupus proliferative nephritis (class III/IV) (ISN/RPS 2003). Direct immunofluorescence microscopy was performed in -80ºC frozen sections to evaluate IgA, IgG, IgM, C4d, C1q and C3, and LES activity and chronicity scores were calculated according to NIH disease activity scoring system. The intensity of staining was graded as 0 (no staining), +1 (stainvisible at 40X magnification), +2 (at 20X), +3 (at X10), and +4 (at 2-4X). For statistical purpose we considered weak staining: 0, +1, +2 and strong staining: +3, +4. Patient´s files were retrospectively reviewed and clinical and analytical data were collected using a standardized form. Results 64 native kidney biopsies from 56 patients with a diagnosis of lupus proliferative nephritis were included, basal characteristics are described in attached Table. Activity index was significantly higher in biopsies showing strong intensity C3 staining compared to biopsies showing weak intensity C3 staining [(n=25) 10±1 vs (n=13) 5±1; p=0.002 respectively], alb/creat was significantly higher in patients in whom biopsy showed strong intensity C3 staining, compared to biopsies showing weak intensity C3 staining [(n=10) 1964.4±585.2 mg/gr vs (n=6) 823.6±58 mg/gr; p<0.001, respectively], prot/creat was significantly higher in biopsies that showed strong C3 staining intensity [(n=27) 2302.5±325 mg/gr vs (n=12) 1287.7±235 mg/gr, p<0.005, respectively], haematuria at NL diagnosis was more frequently in patients whose biopsy showed strong intensity C3 staining (n=21, 80.8%), compared to biopsies showing weak intensity C3 staining (n=5, 19.5%, p<0.001); most of the patients without haematuria at diagnosis showed a weak intensity C3 staining or not C3 staining (n=13, 62%). Endocapillary proliferation was significantly higher in biopsies showing strong intensity C3 staining (90.9% vs 9.1%, p<0.001).Time to proteinuria response is higher in patients showing strong intensity C4d stainingcompared with biopsies showing weak intensity C4d staining (15.2±2.4 vs 6.4±1.8 months; p=0.001), time to haematuria response is higher inbiopsies showing strong intensity C4d staining (19.5±5.5 vs 7.5±2.3 months, p=0.003). Time to proteinuria response is higher in patients showing strong intensity C1q stainingcompared to biopsies showing weak intensity C1q staining (14.0±9 vs 3.3±2.6 months, p <0.001). Conclusion Our results suggest that complement system is activated in kidney tissue of proliferative LN patients; C3 staining is associated with clinical, analytical and histological data related to acute lupus activity, whereas C4d and C1q staining are related with long-term outcomes like treatment response. Further studies are needed to elucidate the role of complement system in LN.