Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

Abstract

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

Integrative analysis of DNA methylation in discordant twins unveils distinct architectures of systemic sclerosis subsets

“…Indeed, both monocytes and macrophages (cell types with the strongest enrichment) play a critical role in fibrosis [71]. The number of circulating monocytes is increased in SSc [72] and correlates with disease progression and severity [73, 74]. The changes in methylation detected in dcSSc are thus impacting the function of regulatory elements in cell types with critical functions in fibrosis.…”

B Cell Homeostasis and Functional Properties Are Altered in an Hypochlorous Acid-Induced Murine Model of Systemic Sclerosis

“…More importantly, the anomalies found in HOCl mice are close to those reported in human SSc. Just as splenic B cell counts are decreased during the early active stage of the experimental protocol, circulating B cell lymphopenia is associated with disease activity and severity in SSc patients ( 27 , 28 ). Characteristic B cell subset modifications in human SSc consist in an expansion of mature naive B cells and a depletion in memory B cells and plasmablasts ( 8 – 12 ), all of which were observed in HOCl mice in our study.…”

The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review

“…Later, another group showed that the percentage of peripheral Mo in SSc is significantly higher than that in healthy controls. Notably, this higher percentage of Mo also correlated with worse prognosis and visceral disease involvement (14). However, in this study, Mo were not detected specifically through CD14 but instead were gated indirectly through CD3 + CD4 − , weakening the general application of this conclusion.…”

“…In fact, Mo or Mϕ infiltration is generally observed in many autoimmune diseases (4–13). Additionally, a change in the count or frequency of Mo/Mϕ is a hallmark of several autoimmune diseases, i.e., systemic sclerosis (SSc), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), Sjögren's syndrome (SS), and inflammatory bowel disease (IBD) (4, 5, 10, 14–17). However, it should be noted that Mo/Mϕ frequency and count in the peripheral blood or afflicted tissues can be affected by several factors including at least bleeding regimes (for instance time of bleeding) and status of the patients (medical treatment, food intake, age, sex etc.).…”