TY - JOUR

T1 - Imbalance in B cell and T Follicular Helper Cell Subsets in Pulmonary Sarcoidosis

AU - Kudryavtsev, I.

AU - Serebriakova, M.

AU - Starshinova, A.

AU - Zinchenko, Y.

AU - Basantsova, N.

AU - Malkova, A.

AU - Soprun, L.

AU - Churilov, L. P.

AU - Toubi, E.

AU - Yablonskiy, P.

AU - Shoenfeld, Y.

N1 - Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/1/23

Y1 - 2020/1/23

N2 - Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016-2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of "naïve" (IgD + CD27-) and activated B cell (Bm2 and Bm2') subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD- CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27-). Next, a significantly higher proportion of CXCR5-expressing CD45RA - CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4- and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells - most effective cell type in supporting B-cell activity, particularly in antibody production - may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.

AB - Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016-2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of "naïve" (IgD + CD27-) and activated B cell (Bm2 and Bm2') subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD- CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27-). Next, a significantly higher proportion of CXCR5-expressing CD45RA - CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4- and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells - most effective cell type in supporting B-cell activity, particularly in antibody production - may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.

KW - Adult

KW - B-Lymphocyte Subsets/cytology

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Lymphocyte Count

KW - Male

KW - Prospective Studies

KW - Sarcoidosis, Pulmonary/blood

KW - T-Lymphocytes, Helper-Inducer/cytology

KW - ANTIBODIES

KW - HUMANS

KW - EXPANSION

UR - http://www.scopus.com/inward/record.url?scp=85078205034&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/ca4ecf2f-e577-3c40-976f-d0c0de4b7f6d/

U2 - 10.1038/s41598-020-57741-0

DO - 10.1038/s41598-020-57741-0

M3 - Article

C2 - 31974463

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 1059

ER -