Objectives: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).
Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): Prospective study / Bruschi, M.; Moroni, G.; Sinico, R. A.; Franceschini, F.; Fredi, M.; Vaglio, A.; Cavagna, L.; Petretto, A.; Pratesi, F.; Migliorini, P.; Locatelli, F.; Pazzola, G.; Pesce, G.; Bagnasco, M.; Manfredi, A.; Ramirez, G. A.; Esposito, P.; Murdaca, G.; Negrini, S.; Cipriani, L.; Trezzi, B.; Emmi, G.; Cavazzana, I.; Binda, V.; D'Alessandro, M.; Fenaroli, P.; Pisani, I.; Garibotto, G.; Montecucco, C.; Santoro, D.; Scolari, F.; Volpi, S.; Mosca, M.; Tincani, A.; Candiano, G.; Prunotto, M.; Verrina, E.; Angeletti, A.; Ravelli, A.; Ghiggeri, G. M.. - In: RHEUMATOLOGY. - ISSN 1462-0324. - 60:7(2021), pp. 3388-3397. [10.1093/rheumatology/keaa793]
Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): Prospective study
Manfredi A.;Ramirez G. A.;
2021-01-01
Abstract
Objectives: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
