Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): Prospective study

M. Bruschi, G. Moroni, R.A. Sinico, F. Franceschini, M. Fredi, A. Vaglio, L. Cavagna, A. Petretto, F. Pratesi, P. Migliorini, F. Locatelli, G. Pazzola, G. Pesce, M. Bagnasco, A. Manfredi, G.A. Ramirez, P. Esposito, G. Murdaca, S. Negrini, L. CiprianiB. Trezzi, G. Emmi, I. Cavazzana, V. Binda, M. D'Alessandro, P. Fenaroli, I. Pisani, G. Garibotto, C. Montecucco, D. Santoro, F. Scolari, S. Volpi, M. Mosca, A. Tincani, G. Candiano, M. Prunotto, E. Verrina, A. Angeletti, A. Ravelli, G.M. Ghiggeri

Research output: Contribution to journalArticlepeer-review

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).

Original languageEnglish
Pages (from-to)3388-3397
Number of pages10
JournalRheumatology (United Kingdom)
Volume60
Issue number7
DOIs
Publication statusPublished - 2021

Keywords

  • anti-C1q antibodies
  • anti-ENO1 antibodies
  • anti-Histone 2A antibodies
  • biomarkers
  • lupus nephritis
  • systemic lupus erythematosus
  • complement component C1q
  • complement component C1q antibody
  • complement component C3
  • complement component C4
  • complement component C4d
  • cyclosporine
  • fibrinogen
  • histone antibody
  • histone H2A
  • histone H3
  • hydroxychloroquine sulfate
  • immunoglobulin G2
  • immunoglobulin M
  • lipocortin 1
  • nucleosome autoantibody
  • rituximab
  • antinuclear antibody
  • autoantibody
  • DNA
  • DNA binding protein
  • ENO1 protein, human
  • enolase
  • histone
  • immunoglobulin G
  • tumor marker
  • tumor suppressor protein
  • adult
  • Article
  • clinical outcome
  • cohort analysis
  • controlled study
  • estimated glomerular filtration rate
  • female
  • fibrinogen blood level
  • follow up
  • histology
  • human
  • human cell
  • human tissue
  • immunofluorescence
  • lupus erythematosus nephritis
  • major clinical study
  • male
  • prospective study
  • proteinuria
  • disease exacerbation
  • immunology
  • middle aged
  • nucleosome
  • Adult
  • Annexin A1
  • Antibodies, Antinuclear
  • Autoantibodies
  • Biomarkers, Tumor
  • Complement C1q
  • Disease Progression
  • DNA-Binding Proteins
  • Female
  • Histones
  • Humans
  • Immunoglobulin G
  • Lupus Erythematosus, Systemic
  • Lupus Nephritis
  • Male
  • Middle Aged
  • Nucleosomes
  • Phosphopyruvate Hydratase
  • Prospective Studies
  • Tumor Suppressor Proteins

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