NK cell count as predictor of clinical response in patients with rheumatoid arthritis treated with rituximab

Abstract

Alfredomaria Lurati, Luca Bertani, Mariagrazia Marrazza, Katia Angela Re, Daniela Bompane, Magda ScarpelliniRheumatology Unit, Fornaroli Hospital, Magenta, ItalyPurpose: The relationship between antiCD20 therapy with rituximab and the lymphocytes phenotype in patients with rheumatoid arthritis was investigated, with an attempt to establish a relationship between commonly used clinical activity indices and variations in leukocyte count, in particular natural killer (NK) lymphocytes.Methods: Patients with seropositive (cyclic citrullinated peptides and rheumatoid factor positive) rheumatoid arthritis (according to the American College of Rheumatology 1987 criteria) refractory to conventional and antitumor necrosis factor-alpha agents who were subsequently treated with rituximab, a chimeric monoclonal antibody directed against CD20, were enrolled between January 2009 and September 2009. All subjects were treated with rituximab standard rheumatologic dose of 1.0 g on days 1 and 15 every 6 months for at least 2 years. A clinical evaluation was performed at baseline and subsequently every 3 months thereafter. At each assessment activated NK (CD56+/CD16+/CD54bright) cell count was collected and disease activity was assessed using Disease Activity Score in 28 Joints and the Simplified Disease Activity Index (SDAI).Results: Thirty-four patients were enrolled (mean age ± standard deviation: 54.8 ± 12.8 years). Basal SDAI was 21.75 ± 5.4 and NK cell count mean value was 157.6 ± 90. After 24 months, SDAI was 14 ± 1.2 and NK cell count mean value was 301.7 ± 21 (P < 0.05). An inverted correlation between SDAI and NK count was observed at 3 months (r = -0.36, P < 0.05), 6 months (r = -0.48, P < 0.45), 9 months (r = -0.47, P < 0.05), 12 months (r = -0.41, P < 0.01), 15 months (r = -0.58, P < 0.05), 18 months (r = -0.53, P < 0.05), 21 months (r = -0.68, P < 0.05), and 24 months (r = -0.61, P < 0.05). A linear regression model between all variables collected and SDAI/Disease Activity Score in 28 Joints at 6 months and 12 months confirmed a significant relationship between SDAI/Disease Activity Score in 28 Joints and NK cell count.Conclusion: The data confirm the clinical efficacy of rituximab and suggests the use of NK cells as a predictor of clinical response in patients with rheumatoid arthritis.Keywords: NK cells, rituximab, predictor, response, rheumatoid arthritis