cholesterol-stearamide-mediate-lymphocyte-apoptosis-cytokine

Cholesterol and Stearamide Mediate Lymphocyte Apoptosis and Cytokine Secretion in Systemic Lupus Erythematosus

Alterations in serum metabolite composition have been increasingly associated with systemic lupus erythematosus (SLE), yet the direct effects of these ...

Shenzhen Traditional Chinese Medicine Hospital

Shenzhen Traditional Chinese Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, the Clinical Medical Research Center of Shenzhen People's Hospital

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients  non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.

Absolute quantification and characterization of oxylipins in lupus nephritis and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting thousands of people. There are still no effective biomarkers for SLE diagnosis and disease activity assessment. We performed proteomics and metabolomics analyses of serum from 121 SLE patients and 106 healthy individuals, and identified 90 proteins and 76 metabolites significantly changed. Several apolipoproteins and the metabolite arachidonic acid were significantly associated with disease activity. Apolipoprotein A-IV (APOA4), LysoPC(16:0), punicic acid and stearidonic acid were correlated with renal function. Random forest model using the significantly changed molecules identified 3 proteins including ATRN, THBS1 and SERPINC1, and 5 metabolites including cholesterol, palmitoleoylethanolamide, octadecanamide, palmitamide and linoleoylethanolamide, as potential biomarkers for SLE diagnosis. Those biomarkers were further validated in an independent cohort with high accuracy (AUC = 0.862 and 0.898 for protein and metabolite biomarkers respectively). This unbiased screening has led to the discovery of novel molecules for SLE disease activity assessment and SLE classification.

Serum proteome and metabolome uncover novel biomarkers for the assessment of disease activity and diagnosing of systemic lupus erythematosus.

Radiotherapy is a pivotal treatment for lung cancer, significantly impacting tumor control and patient quality of life. Despite its benefits, the molecular mechanisms underlying radiotherapy-induced biological alterations in lung cancer cells remain inadequately understood. In this study, we employed a mass spectrometry-based lipidomics approach to investigate lipid profile changes in a lung cancer mouse model post-radiation. Lewis lung carcinoma (LLC) cells were injected into C57BL/6J mice, followed by radiation treatment with varying split doses. Our results showed an increase in sterol lipids and a decrease in glycerolipids, specifically triacylglycerides, indicating disrupted lipid storage. Additionally, we observed significant changes in glycerophospholipid unsaturation, suggesting a remodeling of membrane properties that may influence cell survival. Linear regression analysis demonstrated a significant negative correlation between glycerophospholipid unsaturation index and tumor weight, indicating a potential role in radiation-induced tumor cell death. These findings provide new insights into the lipid metabolic pathways affected by radiotherapy and could inform the development of improved therapeutic strategies for lung cancer treatment.

Lipidome analyses reveal radiation induced remodeling of glycerophospholipid unsaturation in lung tumor.

Autoimmune diseases (AIDs) constitute a group of disorders where the immune system mistakenly attacks the body's tissues. The pathogenesis of AIDs involve a breakdown in immune tolerance, culminating in an immune response that targets autoantigens. In adaptive immunity, secondary rearrangement of T cell receptors (TCRs) and B cell receptors (BCRs) involves sequential V(D)J recombination events during lymphocyte development. Imperfect receptor editing during this process can generate autoreactive clones, thereby contributing to the pathogenesis of AIDs. Emerging evidence implicates secondary V(D)J recombination in TCR and BCR genes as a pathogenic driver in multiple AIDs. The detection of secondary rearrangements, along with targeted therapeutic interventions (e.g. anti-CD40L, IL6), offers novel avenues for the early prediction and diagnosis of these diseases. This article provides a comprehensive overview of the current research on the role of TCR/BCR secondary rearrangements in AIDs, elucidating their mechanisms of action to enhance our understanding of the pathogenesis, diagnosis, and treatment of autoimmune disorders.

Article	Year
Absolute quantification and characterization of oxylipins in lupus nephritis and systemic lupus erythematosus. Frontiers in immunology\| PubMed ID: 36275708	2022
Serum proteome and metabolome uncover novel biomarkers for the assessment of disease activity and diagnosing of systemic lupus erythematosus. Clinical immunology (Orlando, Fla.)\| PubMed ID: 37075949	2023
Lipidome analyses reveal radiation induced remodeling of glycerophospholipid unsaturation in lung tumor. Frontiers in immunology\| PubMed ID: 39512339	2024
TCR/BCR Secondary Rearrangement in Autoimmune Diseases: Molecular Mechanisms, Pathogenic Roles, and Therapeutic Frontiers. Immunological investigations\| PubMed ID: 40916044	2025

Jingquan He

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