Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

the RAVE–Immune Tolerance Network Research Group

Research output: Contribution to journalArticle

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Abstract

Objective: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Methods: Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Results: Patients were divided into 4 groups: proteinase 3 (PR3)–ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)–ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). Conclusion: An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA–positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalArthritis and Rheumatology
Volume69
Issue number1
DOIs
StatePublished - Jan 1 2017

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Leukocyte L1 Antigen Complex
Vasculitis
Antineutrophil Cytoplasmic Antibodies
Peptide Hydrolases
Recurrence
Myeloblastin
Serum
Remission Induction
Peroxidase
Biomarkers
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Azathioprine
Cyclophosphamide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. / the RAVE–Immune Tolerance Network Research Group.

In: Arthritis and Rheumatology, Vol. 69, No. 1, 01.01.2017, p. 185-193.

Research output: Contribution to journalArticle

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title = "Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis",
abstract = "Objective: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Methods: Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Results: Patients were divided into 4 groups: proteinase 3 (PR3)–ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)–ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). Conclusion: An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA–positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment.",
author = "{the RAVE–Immune Tolerance Network Research Group} and Pepper, {Ruth J.} and Draibe, {Juliana B.} and Ben Caplin and Fervenza, {Fernando Custodio} and Hoffman, {Gary S.} and Kallenberg, {Cees G M} and Langford, {Carol A.} and Monach, {Paul A.} and Philip Seo and Robert Spiera and E. William and Tchao, {Nadia K.} and Stone, {John H.} and Ulrich Specks and Merkel, {Peter A.} and Salama, {Alan D.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1002/art.39814",
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pages = "185--193",
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T1 - Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

AU - the RAVE–Immune Tolerance Network Research Group

AU - Pepper, Ruth J.

AU - Draibe, Juliana B.

AU - Caplin, Ben

AU - Fervenza, Fernando Custodio

AU - Hoffman, Gary S.

AU - Kallenberg, Cees G M

AU - Langford, Carol A.

AU - Monach, Paul A.

AU - Seo, Philip

AU - Spiera, Robert

AU - William, E.

AU - Tchao, Nadia K.

AU - Stone, John H.

AU - Specks, Ulrich

AU - Merkel, Peter A.

AU - Salama, Alan D.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Objective: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Methods: Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Results: Patients were divided into 4 groups: proteinase 3 (PR3)–ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)–ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). Conclusion: An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA–positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment.

AB - Objective: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Methods: Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Results: Patients were divided into 4 groups: proteinase 3 (PR3)–ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)–ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). Conclusion: An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA–positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment.

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DO - 10.1002/art.39814

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EP - 193

JO - Arthritis and Rheumatology

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