Columbia University New York, New York, United States
Disclosure(s): No financial relationships with ineligible companies to disclose
Background/Purpose: Sicca symptoms may develop in the setting of immune checkpoint inhibitor (ICI) therapy and are clinically indistinguishable from those encountered in Sjogren’s disease (SjD). B cells are known to play a role in the pathogenesis of SjD and ICI adverse events. We characterized peripheral B cell subsets in patients with these conditions to uncover potential mechanisms of immune dysregulation. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 6 patients (1 healthy control, 1 patient with ICI-sicca syndrome, 4 patients with SjD) and analyzed by flow cytometry. We defined CD19 B-cell subsets on the basis of IgD, CD27, CD24 and CD38. Cells were gated as naïve (further subdivided into Transitional 1, 2, and 3), Unswitched/marginal-zone-like, Class-switched/Plasmablasts and Double Negative. Results: In the differentiated mature B cell compartment (CD27+ IgD−), CD38 hi Plasmablasts and Class-Switched Memory B cells were decreased in all patients as compared to the control (14.4%±5.7 in SjD vs 8.4% in ICI sicca syndrome vs 40.4% in the control) (Figure 1)
In the naive compartment (CD 27- IgD+), the more mature of the naive B cells (Transitional 3 subset, defined as CD 24-CD38-) were similarly decreased in disease as compared to the control ( 77.3%± 6.7 in SjD vs 86.0% in ICI sicca syndrome vs 95.7% in control). Conversely the less mature naive B cells (Transitional 1(CD24+CD38+) and Transitional 2(CD24+CD38−)) were increased in disease relative to the control (Figure 2).
Additionally, the Activated Naïve B cell population was elevated in both diseases, suggesting increased peripheral activation.
In contrast, the percentage of Unswitched Memory (Marginal Zone) B cells and Double Negative Memory B cells were similar between the three groups. Conclusion: In SjD and ICI-sicca syndrome there is an increase in the proportion of the less mature transitional 1 and transitional 2 B cells, with a simultaneous decrease in the proportion of transitional 3 B cells as well as the mature Class Switched memory and Plasmablast subsets. This may suggest a defect in B cell development in disease. The similar findings seen in SjD and ICI-sicca syndrome may suggest a shared pathogenesis between the two conditions.
