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

Ruth J. Pepper, Juliana B. Draibe, Ben Caplin, Fernando C. Fervenza, Gary S. Hoffman, Cees G M Kallenberg, Carol A. Langford, Paul A. Monach, Philip Seo, Robert Spiera, E. William, Nadia K. Tchao, John H. Stone, Ulrich Specks, Peter A. Merkel, Alan D. Salama, the RAVE–Immune Tolerance Network Research Group

Research output: Contribution to journalArticle

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
Myeloblastin
Antineutrophil Cytoplasmic Antibodies
Vasculitis
Recurrence
Serum
Remission Induction
Peroxidase
Biological Markers
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Azathioprine
Cyclophosphamide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Pepper, R. J., Draibe, J. B., Caplin, B., Fervenza, F. C., Hoffman, G. S., Kallenberg, C. G. M., ... the RAVE–Immune Tolerance Network Research Group (2017). Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis and Rheumatology, 69(1), 185-193. DOI: 10.1002/art.39814

Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. / Pepper, Ruth J.; Draibe, Juliana B.; Caplin, Ben; Fervenza, Fernando C.; Hoffman, Gary S.; Kallenberg, Cees G M; Langford, Carol A.; Monach, Paul A.; Seo, Philip; Spiera, Robert; William, E.; Tchao, Nadia K.; Stone, John H.; Specks, Ulrich; Merkel, Peter A.; Salama, Alan D.; 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

Pepper, RJ, Draibe, JB, Caplin, B, Fervenza, FC, Hoffman, GS, Kallenberg, CGM, Langford, CA, Monach, PA, Seo, P, Spiera, R, William, E, Tchao, NK, Stone, JH, Specks, U, Merkel, PA, Salama, AD & the RAVE–Immune Tolerance Network Research Group 2017, 'Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis' Arthritis and Rheumatology, vol 69, no. 1, pp. 185-193. DOI: 10.1002/art.39814
Pepper RJ, Draibe JB, Caplin B, Fervenza FC, Hoffman GS, Kallenberg CGM et al. Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis and Rheumatology. 2017 Jan 1;69(1):185-193. Available from, DOI: 10.1002/art.39814

Pepper, Ruth J.; Draibe, Juliana B.; Caplin, Ben; Fervenza, Fernando C.; Hoffman, Gary S.; Kallenberg, Cees G M; Langford, Carol A.; Monach, Paul A.; Seo, Philip; Spiera, Robert; William, E.; Tchao, Nadia K.; Stone, John H.; Specks, Ulrich; Merkel, Peter A.; Salama, Alan D.; the RAVE–Immune Tolerance Network Research Group / Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis.

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 = "Pepper, {Ruth J.} and Draibe, {Juliana B.} and Ben Caplin and Fervenza, {Fernando C.} 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.} and {the RAVE–Immune Tolerance Network Research Group}",
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T1 - Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

AU - Pepper,Ruth J.

AU - Draibe,Juliana B.

AU - Caplin,Ben

AU - Fervenza,Fernando C.

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.

AU - the RAVE–Immune Tolerance Network Research Group

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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.

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