Objectives: The aim was to study lymphocyte subsets and circulating cytokines at diagnosis of PMR and after tocilizumab monotherapy. Methods: Eighteen untreated patients with PMR were included in a prospective study and received 3-monthly tocilizumab infusions without glucocorticoids. Lymphocyte subset distribution was assessed by flow cytometry and serum cytokines were assayed by a 34-cytokine array and ELISA, at baseline and during follow-up. Baseline data were also compared with age- and sex-matched controls. Results: At baseline, total lymphocytes, T-cell subsets and NK cell counts were similar in patients and controls, but patients had significantly lower B-cell counts attributable to lower transitional, naïve and post-switch memory B-cell subsets. Circulating B-cell counts were positively correlated with the PMR activity score (PMR-AS) in untreated active patients at baseline, but subsequently increased to normal values while disease activity was controlled after tocilizumab therapy. Among serum cytokines, IL-6 showed the largest concentration difference between patients and controls, and the serum IL-6 concentration was correlated with baseline PMR-AS. The effects of tocilizumab on serum IL-6 concentration were heterogeneous, and the patients whose serum IL-6 decreased after tocilizumab therapy exhibited a significant increase in circulating B-cell counts. Conclusion: In patients with PMR, B-cell lymphopenia and abnormal B-cell subset distribution are associated with disease activity and IL-6 concentration, and both are corrected by the IL-6 antagonist tocilizumab.
Objectives: The aim was to study lymphocyte subsets and circulating cytokines at diagnosis of PMR and after tocilizumab monotherapy. Methods: Eighteen untreated patients with PMR were included in a prospective study and received 3-monthly tocilizumab infusions without glucocorticoids. Lymphocyte subset distribution was assessed by flow cytometry and serum cytokines were assayed by a 34-cytokine array and ELISA, at baseline and during follow-up. Baseline data were also compared with age- and sex-matched controls. Results: At baseline, total lymphocytes, T-cell subsets and NK cell counts were similar in patients and controls, but patients had significantly lower B-cell counts attributable to lower transitional, naïve and post-switch memory B-cell subsets. Circulating B-cell counts were positively correlated with the PMR activity score (PMR-AS) in untreated active patients at baseline, but subsequently increased to normal values while disease activity was controlled after tocilizumab therapy. Among serum cytokines, IL-6 showed the largest concentration difference between patients and controls, and the serum IL-6 concentration was correlated with baseline PMR-AS. The effects of tocilizumab on serum IL-6 concentration were heterogeneous, and the patients whose serum IL-6 decreased after tocilizumab therapy exhibited a significant increase in circulating B-cell counts. Conclusion: In patients with PMR, B-cell lymphopenia and abnormal B-cell subset distribution are associated with disease activity and IL-6 concentration, and both are corrected by the IL-6 antagonist tocilizumab.
Authors: Maëlle Le Goff; Divi Cornec; Dewi Guellec; Thierry Marhadour; Valérie Devauchelle-Pensec; Sandrine Jousse-Joulin; Marion Herbette; Jean Michel Cauvin; Clara Le Guillou; Yves Renaudineau; Christophe Jamin; Jacques Olivier Pers; Alain Saraux Journal: PLoS One Date: 2019-02-27 Impact factor: 3.240
Authors: Yannick van Sleen; Jacoba C Graver; Wayel H Abdulahad; Kornelis S M van der Geest; Annemieke M H Boots; Maria Sandovici; Elisabeth Brouwer Journal: Front Immunol Date: 2019-08-22 Impact factor: 7.561