Peripheral-blood b-cell subset disturbances in inflammatory joint diseases induced by Tropheryma whipplei

Objective To look for abnormalities in circulating B-cell subsets in patients with rheumatic symptoms of Whipple's disease (WD). Method Consecutive patients seen between 2010 and 2016 for suspected inflammatory joint disease were identified retrospectively. Results of standardized immunological and serological tests and of peripheral-blood B-cell and T-cell subset analysis by flow cytometry were collected. Patients with criteria suggesting WD underwent PCR testing for Tropheryma whipplei, and those with diagnosis of WD (cases) were compared to those without diagnosis (controls). We used ROC curve analysis to evaluate the diagnostic value of flow cytometry findings for WD. Results Among 2917 patients seen for suspected inflammatory joint disease, 121 had suspected WD, including 9 (9/121, 7.4%) confirmed WD. Proportions of T cells and NK cells were similar between suspected and confirmed WD, whereas cases had a lower proportion of circulating memory B cells (IgD(-)CD38(low), 18.0%+/- 9.7% vs. 26.0%+/- 14.2%, P = 0.041) and higher ratio of activated B cells over memory B cells (4.4 +/- 2.0 vs. 2.9 +/- 2.2, P = 0.023). Among peripheral-blood B-cells, the proportion of IgD+CD27- naive B cells was higher (66.2%+/- 18.2% vs. 54.6%+/- 18.4%, P = 0.047) and that of IgD-CD27+ switched memory B cells lower (13.3%+/- 5.7% vs. 21.4%+/- 11.9%, P = 0.023), in cases vs. controls. The criterion with the best diagnostic performance was a proportion of IgD+CD27- naive B cells above 70.5%, which had 73% sensitivity and 80% specificity. Conclusion Our study provides data on peripheral-blood B-cell disturbances that may have implications for the diagnosis and pathogenetic understanding of WD.