We have previously revealed that the expression of various glycosylation enzymes is altered in patients with activeSLE. This finding could be linked to a decreased sensitivity of SLE activated T-cells to the immunoregulatory lectin Galectin-1. Herein, we wished to obtain an overview of the expression of a wide spectrum of glycosylation enzymes and lectins in patients with active SLE recruited within the multinational European PRECISESADS project.
Clinical data and RNA reads from PRECISEADS study were collected from 230 SLE patients and 444 controls. Total RNA was extracted from whole blood samples, RNASeq analysis was performed. In this study, the RNASeq data were investigated using a differential gene expression bioinformatics pipeline, and SLE subgroups stratified as those with high (SLEDAI≥6), moderate (SLEDAI=3-5) or low (SLEDAI=0-2) disease activity, and healthy controls were compared. The pathway and ontology enrichment of genes with significant expression change where investigated by Ingenuity Pathway Analysis software.
Despite sporadic differences, glycosylation enzyme mRNA expression was not systematically different from controls in active SLE patients. However, Siglec-1, a sialic acid binding lectin was upregulated, whereas Collectin-12, a sialic acid containing scavenger receptor was downregulated in patients with high disease activity as compared with controls (Siglec-1) or with all other groups (Collectin-12) (p<0.05). Both substances are interferon-inducible. TUSC3, an enzyme participating in glycosylation was down-regulated. Pathway analysis revealed interferon (IF1H1)- and cytosolic pattern recognition receptor-related pathways to be most strongly involved.
Some participants in lectin-mediated immunoregulation with potential pathogenetic significance are differentially expressed in patients with active SLE.