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

Date Published: February 27, 2019

Publisher: Public Library of Science

Author(s): 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, Yolande Richard.

http://doi.org/10.1371/journal.pone.0211536

Abstract

To look for abnormalities in circulating B-cell subsets in patients with rheumatic symptoms of Whipple’s disease (WD).

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.

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-CD38low, 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.

Our study provides data on peripheral-blood B-cell disturbances that may have implications for the diagnosis and pathogenetic understanding of WD.

Partial Text

Whipple’s disease (WD) is a rare, systemic, disease caused by the intracellular Gram-positive bacterium Tropheryma whipplei (TW). This ubiquitous commensal organism [1] is transmitted among humans via the oro-fecal route [2,3]. WD was first described in 1907. TW was identified by polymerase chain reaction (PCR) in small-bowel biopsies from patients with WD [4–7] in 1991 and later in various samples including stool, saliva, and joint fluid [8, 9]. T. whipplei is extraordinarily difficult and slow to grow in cultures. The prevalence of TW carriage is highest in adults, residents of rural areas, and exposed individuals such as homeless people and sewer workers [2, 10]. In apparently healthy individuals, the prevalence of carriers identified by PCR screening of stool and saliva was 1.5% to 7.0% and 0.2% to 1.5%, respectively [11–13].

In patients with WD and rheumatic symptoms, the distribution of peripheral-blood B-cell subsets differed from that in controls with inflammatory joint disease. No differences were found, in contrast, for total lymphocytes, T cells, or NK cells. The cases had lower proportions of circulating IgD-CD38-/low memory B cells and, most notably, of IgD-CD27+switched memory B cells. The ratio of IgD+CD38+/hi activated B cells over IgD-CD38-/low memory B cells was higher in the cases, because of a higher percentage of IgD+CD27- naive B cells. The best diagnostic performance was obtained for an IgD+CD27- naive B-cell proportion at or above 70.5%. The B-cell subset abnormalities documented in our study may provide diagnostic assistance, in combination with the medical history, physical findings, and standard laboratory tests. Furthermore, they may help to understand the pathophysiology of WD. In our population, patients with other infectious diseases did not have the B-cell subset abnormalities seen in the patients with WD.

 

Source:

http://doi.org/10.1371/journal.pone.0211536

 

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