Gene expression analysis revealed downregulation of complement receptor 1 in clonal B cells in cold agglutinin disease.
Agnieszka MałeckaIngunn ØstlieGunhild TrøenJędrzej MałeckiJan DelabieAnne TierensLudvig A MuntheSigbjørn BerentsenGeir E TjønnfjordPublished in: Clinical and experimental immunology (2024)
Cold agglutinin disease (CAD) is a rare B-cell lymphoproliferative disorder of the bone marrow, manifested by autoimmune hemolytic anemia caused by binding of monoclonal IgM autoantibodies to the I antigen. Underlying genetic changes have previously been reported, but their impact on gene expression profile has been unknown. Here, we define differentially expressed genes in CAD B cells. To unravel downstream alteration in cellular pathways, gene expression by RNA sequencing was undertaken. Clonal B-cell samples from 12 CAD patients and IgM-expressing memory B cells from 4 healthy individuals were analyzed. Differential expression analysis and filtering resulted in 93 genes with significant differential expression. Top upregulated genes included SLC4A1, SPTA1, YBX3, TESC, HBD, AHSP, TRAF1, HBA2, RHAG, CA1, SPTB, IL10, UBASH3B, ALAS2, HBA1, CRYM, RGCC, KANK2, and IGHV4-34. They were upregulated at least 8-fold, while complement receptor 1 (CR1/CD35) was downregulated 11-fold in clonal CAD B cells compared to control B cells. Flow cytometry analyses further confirmed reduced CR1 (CD35) protein expression by clonal CAD IgM+ B cells compared to IgM+ memory B cells in controls. CR1 (CD35) is an important negative regulator of B-cell activation and differentiation. Therefore, reduced CR1 (CD35) expression may increase activation, proliferation, and antibody production in CAD-associated clonal B cells.
Keyphrases
- coronary artery disease
- gene expression
- genome wide
- genome wide identification
- dna methylation
- bone marrow
- flow cytometry
- end stage renal disease
- chronic kidney disease
- transcription factor
- nk cells
- single cell
- systemic lupus erythematosus
- poor prognosis
- multiple sclerosis
- mesenchymal stem cells
- ejection fraction
- binding protein
- epstein barr virus
- long non coding rna
- peritoneal dialysis
- dna binding
- drug induced