title: Rituximab increases peripheral natural killer cells in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  The clinical response of rituximab (RTX) is related to the degree of B cell depletion, although other circulating lymphocytes may be affected. We investigated the changes in lymphocyte sub-populations in rheumatoid arthritis (RA) patients treated with RTX and their relationship with the therapeutic response, with attention to natural killer (NK) cells.
  
  
  METHODS
  In fifty-one RA patients peripheral blood B and T lymphocytes and NK cells subtypes were counted by flow cytometry before and 3, 6 and 12 months after RTX administration. Patients were evaluated for disease activity with DAS28-CRP and EULAR response criteria at each visit.
  
  
  RESULTS
  RTX significantly increased from baseline values CD56+3- cells (28 %, 19 % and 25 %; p<0.001, p=0.009 and p=0.004 respectively for month 3, 6 and 12) and CD56dimCD16+ cells (41%, 24% and 36%; p<0.001, p=0.001 and p<0.001 respectively for month 3, 6 and 12). CD56bri16- cells were unaffected by RTX treatment. The increase in both CD56+3- and CD56dimCD16+ cells was significantly greater in patients who were re-treated with another course of RTX at month 6 (p=0.046 and p=0.010 respectively). An inverse correlation between disease activity score and increase in NK cells was demonstrated. No significant changes were observed in CD3+, CD4+ and CD8+ cells during the whole observation period.
  
  
  CONCLUSIONS
  In RA patients, RTX treatment is associated with significant and persistent increase in CD56+3- and CD56dimCD16+ NK cells. A correlation with disease activity is probable, although the association with clinical response remains to be proved.
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy. alessandrogiollo@gmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giollo
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Viapiana
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carletto
authors.affiliation: Immunology Unit, Department of Pathology, University of Verona, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ortolani
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Biasi
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gatti
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D019002:CD56 Antigen / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017452:Receptors, IgG / Q000097:blood; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C522918:NCAM1 protein, human; D017452:Receptors, IgG; D000069283:Rituximab