Lymphocyte subsets in the peripheral blood are disturbed in systemic sclerosis patients and can be changed by immunosuppressive medication

Abstract

Systemic sclerosis (SSc) is a severe chronic disease with a broad spectrum of clinical manifestations. SSc displays disturbed lymphocyte homeostasis. Immunosuppressive medications targeting T or B cells can improve disease manifestations. SSc clinical manifestations and immunosuppressive medication in itself can cause changes in lymphocyte subsets. The aim of this study was to investigate peripheral lymphocyte homeostasis in SSc with regards to the immunosuppression and to major organ involvement. 44 SSc patients and 19 healthy donors (HD) were included. Immunophenotyping of peripheral whole blood by fluorescence-activated cell sorting was performed. Cytokine secretions of stimulated B cell cultures were measured. SSc patients without immunosuppression compared to HD displayed lower γδ T cells, lower T helper cells (CD3+/CD4+), lower transitional B cells (CD19+/CD38++/CD10+/IgD+), lower pre-switched memory B cells (CD19+/CD27+/IgD+), and lower post-switched memory B cells (CD19+/CD27+/IgD−). There was no difference in the cytokine production of whole B cell cultures between SSc and HD. Within the SSc cohort, mycophenolate intake was associated with lower T helper cells and lower NK cells (CD56+/CD3−). The described differences in peripheral lymphocyte subsets between SSc and HD generate further insight in SSc pathogenesis. Lymphocyte changes under effective immunosuppression indicate how lymphocyte homeostasis in SSc might be restored.

Human B-cell subset identification and changes in inflammatory diseases

“…4D ) [ 6 , 9 ]. As well as SLE, reduced frequencies of MZB have also been reported in SS, SSc, and COVID-19 [ 9 , 55 , 56 , 58–60 , 135 ]. The factors that result in this depletion in blood are not understood and could represent reduced cell survival or genesis, altered tissue distribution or increased differentiation into ASCs.…”

“…Uncertainty regarding the developmental origin and functional status of MZB cells is reflected by the plethora of names assigned to this subset in the literature. These include unswitched memory [ 56 , 130 , 131 ], pre-switched memory [ 58 , 119 , 132 ], non-switched [ 133 , 134 ], natural effector [ 64 , 135 ], and IgM memory [ 136 , 137 ] B cells. MZB have a CD27 + IgD + IgM + surface phenotype and have high expression of CD1c, CD21, and CD45RB ( Fig.…”

Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation

“…In summary, patients with ES silicosis present a decrease in memory B lymphocytes, naïve T helper cells, and the CD4+/CD8+ ratio and an increase in regulatory T cells and plasmablasts. Compared to other chronic lung diseases with progressive fibrosis, a reduction in memory B cells was also observed in sarcoidosis [ 44 , 45 , 46 ] and systemic sclerosis (SSc) [ 47 ] but not in idiopathic pulmonary fibrosis (IPF) [ 48 ]. The plasmablast number has been reported not to be altered in SSc [ 47 ] or diminished in sarcoidosis [ 45 , 46 ] but is increased in IPF [ 49 ].…”

“…Compared to other chronic lung diseases with progressive fibrosis, a reduction in memory B cells was also observed in sarcoidosis [ 44 , 45 , 46 ] and systemic sclerosis (SSc) [ 47 ] but not in idiopathic pulmonary fibrosis (IPF) [ 48 ]. The plasmablast number has been reported not to be altered in SSc [ 47 ] or diminished in sarcoidosis [ 45 , 46 ] but is increased in IPF [ 49 ]. Regarding T cells, in sarcoidosis, as in our study, reduced naive CD4+ cells, increased CD8+ cells, and consequently a reduced CD4+/CD8+ ratio and an increase in Tregs were also observed [ 50 , 51 , 52 , 53 ].…”

Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis

“…It inhibits their proliferation and therefore suppresses immune-associated responses and antibody formation [ 114 ]. Indeed, SSc patients receiving MMF exhibit decreased numbers of T helper cells (implicated in various SSc pathogenic manifestations) compared to patients with no immunosuppressive treatment [ 115 ]. Strikingly, MMF treatment inhibits the infiltration of myeloid cells including tissue-resident macrophages in the skin of patients with SSc.…”