title: Serum levels of granzyme B decrease in patients with rheumatoid arthritis responding to abatacept.
abstract: OBJECTIVE
  A possible role of granzyme B (GZMB) in the pathogenesis of joint erosions in rheumatoid arthritis (RA) has been suggested. Since CD28neg T-cells may be an important source of GZMB, and we have previously shown that co-stimulation blockade by abatacept can prevent the generation of the CD28neg T-cell populations, we evaluated the effect of abatacept therapy on GZMB serum levels in patients with RA.
  
  
  METHODS
  The serum levels of GZMB were evaluated by an indirect solid-phase enzyme immunoassay before the start of treatment with abatacept (T0) in 53 patients with RA and after 6 months of therapy (T6) in 25 patients.
  
  
  RESULTS
  At T0, GZMB serum levels were correlated with disease activity measured by DAS28-CRP (p=0.0022) and percentages of circulating CD4+CD28neg and CD8+CD28neg T-cells (p=0.007; p=0.031). The levels of GZMB in 18 patients with a moderate or good EULAR clinical response to ABA significantly decreased from T0 to T6 (p=0.023), whereas no variation was observed in 7 non responders. The variation of GZMB levels was directly correlated with that of DAS28-PCR (p=0.040), but not with those of circulating CD28-neg T-cell subsets.
  
  
  CONCLUSIONS
  Costimulation blockade by ABA can decrease the serum levels of GZMB in RA patients responding to the treatment, suggesting that this might be one of the mechanism by which abatacept can prevent radiographic erosions. However, the lack of correlation of such decrease with the numbers of circulating CD28-neg T cells suggests that these cells probably are not the main source of serum GZMB.
authors.affiliation: Rheumatology and Clinical Immunology, University and Spedali Civili of Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Colombo
authors.affiliation: Rheumatology and Clinical Immunology, University and Spedali Civili of Brescia, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Scarsi
authors.affiliation: Rheumatology and Clinical Immunology, University and Spedali Civili of Brescia; and Rheumatology Chair, University of Pavia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Piantoni
authors.affiliation: Rheumatology and Clinical Immunology, University and Spedali Civili of Brescia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.affiliation: Rheumatology and Clinical Immunology, University and Spedali Civili of Brescia, Italy. airo@bresciareumatologia.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D000069594:Abatacept; C509213:GZMB protein, human; D053804:Granzymes