Correction of abnormal B-cell subset distribution by interleukin-6 receptor blockade in polymyalgia rheumatica.
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.
['Carvajal Alegria|Guillermo|G|', 'Devauchelle-Pensec|Valérie|V|', 'Renaudineau|Yves|Y|', 'Saraux|Alain|A|', 'Pers|Jacques-Olivier|JO|', 'Cornec|Divi|D|']
D000368:Aged D061067:Antibodies, Monoclonal, Humanized D016175:B-Lymphocyte Subsets D016022:Case-Control Studies D016207:Cytokines D004797:Enzyme-Linked Immunosorbent Assay D005260:Female D005434:Flow Cytometry D005602:France D006801:Humans D015850:Interleukin-6 D008297:Male D008875:Middle Aged D011111:Polymyalgia Rheumatica D011446:Prospective Studies D012720:Severity of Illness Index D016176:T-Lymphocyte Subsets
interleukin-6 polymyalgia rheumatica cytokines tocilizumab B cells