Dataset Information

Enrichment of complement, immunoglobulins, and autoantibody targets in the proteome of platelets from patients with Systemic Lupus Erythematosus (SLE).

ABSTRACT: SLE is a complex disease characterized by autoimmunity towards apoptotic cells, excessive amounts of circulating immune complexes and complement activation. Decreased platelet size has been observed in SLE and their non-hemostatic functions may play an active role in the disease. Our main objective in this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

DISEASE(S): Systemic Lupus Erythematosus

SUBMITTER: Charlotte Welinder

LAB HEAD: Petrus Linge

PROVIDER: PXD031202 | Pride | 2022-05-20

REPOSITORIES: Pride

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Publications

Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus.

Linge Carl Petrus CP Jern Andreas A Tydén Helena H Gullstrand Birgitta B Yan Hong H Welinder Charlotte C Kahn Robin R Jönsen Andreas A Semple John W JW Bengtsson Anders A AA

Thrombosis and haemostasis 20220413 9

<h4>Background</h4> Systemic lupus erythematosus (SLE) is a complex disease characterized by autoimmunity toward apoptotic cells, excessive amounts of circulating immune complexes, and complement activation. A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome.<h4>Methods</h4> ...[more]

PMID: 35419777

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Project description:Background: The clinical heterogeneity of SLE with its complex pathogenesis remains challenging as we strive to provide optimal management. The contribution of platelets to endovascular homeostasis, inflammation and immune regulation highlights their potential importance in SLE. Prior work from our group showed that the Fcγ receptor type IIa (FcγRIIa)–R/H131 biallelic polymorphism is associated with increased platelet activity and cardiovascular risk in SLE. The study was initiated to investigate the platelet transcriptome in patients with SLE and evaluate its association across FcγRIIa genotypes and distinct clinical features. Methods: Fifty-one patients fulfilling established criteria for SLE (mean age = 41.1±12.3, 100% female, 45% Hispanic, 24% black, 22% Asian, 51% white, mean SLEDAI = 4.4±4.2 at baseline) were enrolled and compared with 18 demographically matched control samples. The FCGR2a receptor was genotyped for each sample, and RNA-seq was performed on isolated, leukocyte-depleted platelets. Transcriptomic data were used to create a modular landscape to explore the differences between SLE patients and controls and various clinical parameters in the context of FCGR2a genotypes. Results: There were 2,290 differentially expressed genes enriched for pathways involved in interferon signaling, immune activation, and coagulation when comparing SLE samples vs controls. When analyzing patients with proteinuria, modules associated with oxidative phosphorylation and platelet activity were unexpectedly decreased. Furthermore, genes that were increased in SLE and in patients with proteinuria were enriched for immune effector processes, while genes increased in SLE but decreased in proteinuria were enriched for coagulation and cell adhesion. A low-binding FCG2Ra allele (R131) was associated with decreases in FCR activation, which further correlated with increases in platelet and immune activation pathways. Finally, we were able to create a transcriptomic signature of clinically active disease that performed significantly well in discerning SLE patients with active clinical disease form those with inactive clinical disease. Conclusions: In aggregate, these data demonstrate the platelet transcriptome provides insight into lupus pathogenesis and disease activity, and shows potential use as means of assessing this complex disease using a liquid biopsy.

Dataset Information

Enrichment of complement, immunoglobulins, and autoantibody targets in the proteome of platelets from patients with Systemic Lupus Erythematosus (SLE).

Publications

Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus.

Similar Datasets

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