Background/Purpose:

Abnormalities in B-cell population distribution were recently reported in polymyalgia rheumatica (PMR) and giant cell arteritis, which improved with glucocorticoids. Our objective here was to analyze the subsets of lymphocytes in patients with PMR and to follow their evolution after tocilizumab treatment.

Methods:

The TENOR study was an open labelled prospective trial including patients with recent PMR fulfilling the Chuang criteria. The disease duration was less than 12 months, and patients had active disease and were glucocorticoids (GCs) free. Patients with suspected giant cell arteritis were excluded. Patients were treated with tocilizumab infusions (week 0, 4 and 8) without GCs (period 1) and then by low-dose GCs from week 12 to week 24 (period 2). All patients were in clinical remission at the end of period 1 (tocilizumab monotherapy). Peripheral blood lymphocyte profiling was performed by multicolor flow cytometry in 18 patients at week (W) 0 (before first tocilizumab infusion), W2, W12 and W24. They were compared to 16 sex and age-matched healthy controls.

Results:

At baseline, total lymphocyte (p=0.31), T cell (p=0.46), B cell (p=0.08) and NK cell (p=0.905) levels were similar between PMR patients and controls. Transitional B cells (CD24^high, CD38^high) and mature-naïve B cells (CD24^low, CD38^low) were lower in patients with PMR than in controls, 3±6 vs 6±6 per mm³ (p=0.01) and 46±41 vs 92±53 per mm³ (p=0.01), respectively. After tocilizumab, total lymphocyte count slightly increased (1739 ± 539/mm³ at W0, 2030 ±591/mm³ at W2, 2068 ±775/mm³ at W12, and 2031 ± 584/mm³ at W24, p<0.01). The absolute number of T cells and CD8⁺ T cells rose between W0 and W24, from 1295 ±405/mm³ to 1541 ±429/mm³ (p=0.03) and from 357 ±215/mm³ to 446 ±328/mm³ (p=0.04) respectively, but proportions were unchanged. The absolute number and proportion of CD4⁺ T cells and NK cells were unaffected by the treatment. In contrast, both absolute number and proportion of B cells increased between W0 and W12, respectively from 176±105/mm³ to 260 ±192/mm³ (p=0.004) and from 10.1% to 13.0% (p<0.001). Among B-cell subsets, these modifications were mainly attributable to the variations of the memory compartment. Unswitched (IgD+CD27+) and switched (IgD-CD27+) memory B-cell absolute number and proportions significantly increased after tocilizumab (p<0.001).

Conclusion:

The drastic clinical improvement following tocilizumab monotherapy in PMR patients is paralleled by an increase in peripheral blood memory B cells. These observations suggest that B cells are involved in disease pathophysiology, and that IL-6 blockade could restore B-cell homeostasis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/abnormal-b-cell-distribution-is-improved-by-tocilizumab-monotherapy-in-patients-with-polymyalgia-rheumatica/