GRN and KLRB1 define a shared peripheral-blood transcriptomic signature linking SLE and IPF

Area of Science:

• Immunology
• Genomics
• Translational Medicine

Background:

• Systemic lupus erythematosus (SLE) and idiopathic pulmonary fibrosis (IPF) share immune-inflammatory characteristics.
• The precise transcriptomic signatures in peripheral blood that connect SLE and IPF are not fully understood.

Purpose of the Study:

• To identify shared gene expression programs in peripheral blood that link SLE and IPF.
• To prioritize reliable markers for both diseases.
• To develop and validate diagnostic models using these markers.

Main Methods:

• Analysis of peripheral blood transcriptomes from discovery and validation cohorts for SLE and IPF.
• Utilized differential expression analysis and weighted gene co-expression network analysis (WGCNA).
• Developed parsimonious gene panels using consensus feature selection methods (LASSO, SVM-RFE, random forest) and validated models across multiple cohorts and experimental settings.

Main Results:

• Identified 43 concordantly regulated shared differentially expressed genes (DEGs) and 43 shared module genes, forming a pool of 78 candidate genes enriched for B-cell and myeloid pathways.
• Developed a 6-gene panel for SLE and a 4-gene panel for IPF, achieving high area under the curve (AUC) values in discovery and validation cohorts.
• Experimental validation confirmed gene panel dysregulation and elevated serum granulin (GRN) in SLE patients, correlating with disease activity markers.

Conclusions:

• Granulin (GRN) and KLRB1 are key components of a shared peripheral blood transcriptomic signature connecting SLE and IPF.
• The developed diagnostic models demonstrate robust validation across multiple cohorts and experimental evidence.
• Model performance varies in different inflammatory conditions, highlighting the need for context-specific interpretation and validation.