Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis.

Yoshiyuki Akiyama,Teppei Morikawa,Daichi Maeda,Atsuhito Nakayama,Yukako Shintani,Yukio Homma,Masashi Fukayama,Akira Nomiya,Yasuhiko Igawa,Aya Niimi

doi:10.1038/srep28652

Yoshiyuki Akiyama, Teppei Morikawa + Show 8 more

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https://doi.org/10.1038/srep28652

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An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of Hunner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder.

Highlights

Interstitial cystitis (IC) is a chronic bladder disease characterized by lower urinary tract symptoms such as urinary frequency, nocturia, urgency, and/or bladder pain, causing a deterioration in the sufferer’s quality of life[1]
We demonstrated that (1) the number or density of CXCR3-positive cells showed no significant differences between Hunner type interstitial cystitis (HIC) and non-IC cystitis specimens; and (2) the majority of accumulating plasma cells expressed CXCR3 in HIC specimens, but not in non-IC cystitis specimens
Lack of difference in the density of CXCR3-positive cells between IC and non-IC specimens may be contradictory to a previous report[11], which indicated increased mRNA expression of genes related to the CXCR3 pathway in the IC bladder

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Introduction

Interstitial cystitis (IC) is a chronic bladder disease characterized by lower urinary tract symptoms such as urinary frequency, nocturia, urgency, and/or bladder pain, causing a deterioration in the sufferer’s quality of life[1]. HIC is a distinct inflammatory disease characterized by predominant infiltration of lymphoplasmacytic cells and denudation of the urothelium among IC7–9. We have examined these features by quantitative evaluation of cell numbers using novel image analysis software, confirming the accumulation of plasma cells in the lamina propria of the HIC bladder[9]. The CXCR3 pathway plays a crucial role in the persistent chronic inflammation seen, for example, in allergic and autoimmune diseases, because of its major chemoattractant properties in recruitment of inflammatory cells[12,13,14,15]. To further characterize the inflammatory reaction in HIC, we examined CXCR3 expression of infiltrating immune cells in HIC specimens by immunohistochemistry using non-IC cystitis specimens as a control

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