Abstract
Background Hunner’s interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC.MethodsThe GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560.ResultsSix types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner’s lesion and non-Hunner’s lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen–antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560.ConclusionThis was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.
Highlights
Hunner’s interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy
Resting mast cells correlated positively with macrophages M2 (r = 0.7) and natural killer (NK) cells activated (0.59) and negatively with T cell follicular helper cell (Tfh) cells (r = –0.42), activated CD4+ memory T cells (r = –0.81), and M0 macrophages (r = –0.53). These results suggest that the function of resting mast cells activated CD4 + memory T cells, Tfh cells, and M0 macrophages in HIC may be antagonistic
0.82 0.80 0.77 0.77 0.77 0.76 0.75 0.74 0.73 0.70 0.68 0.68 0.65 0.61 0.61 0.60 0.59 0.59 0.58 0.58 0.58 0.56 0.56 0.54 0.51 0.50 0.46 0.45 0.44 0.39 0.37 0.37 0.33 p value adjusted. These findings suggest that Tfh cells may serve as a HIC
Summary
Hunner’s interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. We used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. Interstitial cystitis (IC), known as bladder pain syndrome (BPS), is a chronic condition characterized by painful lower urinary tract symptoms [1]. Abnormal immunity is a wellknown histological feature of HIC [5]. Several gene expression studies credibly indicated dysfunctional inflammatory cytokines and autoimmune pathways HIC [6, 7]. Studies showed that immune cells and autoantibodies are closely related to IC/HIC [10, 11]
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