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Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus.

ABSTRACT: Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations.A total of 168 patients with ? 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry.The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ?4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman's rho -0.233, P = 0.02).Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients.

SUBMITTER: Dahdal S

PROVIDER: S-EPMC5783342 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus.

Dahdal Suzan S Devetzis Vasilios V Chalikias George G Tziakas Dimitrios D Chizzolini Carlo C Ribi Camillo C Trendelenburg Marten M Eisenberger Ute U Hauser Thomas T Pasch Andreas A Huynh-Do Uyen U Arampatzis Spyridon S

PloS one 20180124 1

<h4>Background</h4>Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations.<h4>Methods</h4>A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort ...[more]

PMID: 29364894

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Project description:Systemic lupus erythematosus (SLE) is characterized by abnormalities in B cell and T cell function, but the role of disturbances in the activation status of macrophages (M?) has not been well described in human patients. To address this, gene expression profiles from isolated lymphoid and myeloid populations were analyzed to identify differentially expressed (DE) genes between healthy controls and patients with either inactive or active SLE. While hundreds of DE genes were identified in B and T cells of active SLE patients, there were no DE genes found in B or T cells from patients with inactive SLE compared to healthy controls. In contrast, large numbers of DE genes were found in myeloid cells (MC) from both active and inactive SLE patients. Among the DE genes were several known to play roles in M? activation and polarization, including the M1 genes STAT1 and SOCS3 and the M2 genes STAT3, STAT6, and CD163. M1-associated genes were far more frequent in data sets from active versus inactive SLE patients. To characterize the relationship between M? activation and disease activity in greater detail, weighted gene co-expression network analysis (WGCNA) was used to identify modules of genes associated with clinical activity in SLE patients. Among these were disease activity-correlated modules containing activation signatures of predominantly M1-associated genes. No disease activity-correlated modules were enriched in M2-associated genes. Pathway and upstream regulator analysis of DE genes from both active and inactive SLE MC were cross-referenced with high-scoring hits from the drug discovery Library of Integrated Network-based Cellular Signatures (LINCS) to identify new strategies to treat both stages of SLE. A machine learning approach employing MC gene modules and a generalized linear model was able to predict the disease activity status in unrelated gene expression data sets. In summary, altered MC gene expression is characteristic of both active and inactive SLE. However, disease activity is associated with an alteration in the activation of MC, with a bias toward the M1 proinflammatory phenotype. These data suggest that while hyperactivity of B cells and T cells is associated with active SLE, MC potentially direct flare-ups and remission by altering their activation status toward the M1 state.

Dataset Information

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus.

Publications

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus.

Similar Datasets

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