title: Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: University College London Centre for Nephrology, Royal Free Hospital, London, UK.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Pepper
authors.affiliation: University College London Centre for Nephrology, Royal Free Hospital, London, UK.
authors.forename: Juliana B
authors.initials: JB
authors.lastname: Draibe
authors.affiliation: University College London Centre for Nephrology, Royal Free Hospital, London, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Caplin
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.affiliation: University of Groningen, Groningen, The Netherlands.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Langford
authors.affiliation: Boston University, Boston, Massachusetts.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.affiliation: Hospital for Special Surgery, New York, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: E
authors.initials: E
authors.lastname: William St Clair
authors.affiliation: Immune Tolerance Network, San Francisco, California.
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Tchao
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: University College London Centre for Nephrology, Royal Free Hospital, London, UK.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Salama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000188:drug therapy*; D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D011237:Predictive Value of Tests; D012008:Recurrence; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D007155:Immunologic Factors; D039841:Leukocyte L1 Antigen Complex; D000069283:Rituximab; D053146:Myeloblastin