Abstract
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.
Highlights
Sarcoidosis is a multisystem granulomatous disease of an unknown etiology
We evaluated the percentages of circulating B-cell subsets using two major classification schemes based on the relative co-expression of either IgD and CD38
Compared with healthy controls (HC), sarcoidosis patients had a significantly increased frequency of CD5 + CD27− cell in circulation (17.41% (12.28; 21.45) vs. 8.21% (5.55; 12.01), respectively, p < 0.001, Fig. 3c). These findings indicate that at least two B cell subsets – CD24+++ CD38+++ and CD5 + CD27−, that according to the literary data were enriched with IL-10-producing cells – are strongly increased in sarcoidosis patients
Summary
Sarcoidosis is a multisystem granulomatous disease of an unknown etiology. The hallmark of this disease is the presence of non-caseating granulomas that frequently have a pulmonary localization. ® treatment with anti-B-cell agents (anti-CD20 antibody, Rituximab ) showed a clinical improvement in patients with sarcoidosis suggesting that “naïve” and/or memory B cells may play an important role in this disease[13,14]. B-cell involvement in sarcoidosis is rather well documented, but still nothing is known about the part of T follicular helper (Tfh) cells in this disease – the major helper T cell subset that considered to be involved in humoral adaptive immune response[15,16,17]. Recent studies have demonstrated that alterations in circulating Tfh cell subsets have significant effects on the progression of numerous autoimmune diseases[20,21,22,23]. 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
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