Abnormal distribution of AQP5 in labial salivary glands is associated with poor saliva secretion in patients with Sjögren's syndrome including neuromyelitis optica complicated patients

Yoshimura, Shunsuke; Nakamura, Hideki; Horai, Yoshiro; Nakajima, Hideki; Shiraishi, Hiroaki; Hayashi, Tomayoshi; Takahashi, Toshiyuki; Kawakami, Atsushi

doi:10.3109/14397595.2015.1083146

Cited by 41 publications

(32 citation statements)

References 31 publications

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“…AQP5 is localized apically in healthy acinar cell clusters (Figure 1f, inset). In pSS tissue, these conventional acini demonstrated some dysregulation of AQP5 localization, in line with other studies of the minor SGs, but maintained their large cytoplasm:nucleus ratio (22). Acinar clusters in pSS tissue also contained occasional CK7 + cells.…”

Section: Lack Of Conventional Acinar Cells and Skewing Of The Epithelsupporting

confidence: 88%

Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor

et al. 2020

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Background: Salivary glands (SGs) can be damaged by immune checkpoint inhibitor (ICI) therapy. In patients with ICI-induced SG dysfunction, 60% progress to fulfill classification criteria for primary Sjögren's syndrome (pSS), owing to immune foci in SGs and/or anti-SSA autoantibody positivity. We report the SG tissue analysis of a patient with SG dysfunction after treatment with a programmed death ligand-1 (PD-L1) inhibitor, compared to that of a dry mouth ("sicca") control and pSS patient.Case presentation: The patient received the PD-L1 inhibitor durvalumab (10 mg/kg, every 2 weeks by intravenous infusion) as adjuvant treatment for stage 3 non-small cell lung carcinoma, following concurrent chemo radiotherapy. At 43 weeks after 21 cycles of Durvalumab, the patient was not capable of producing unstimulated or stimulated parotid gland saliva, and a biopsy was taken. Immunohistochemical analysis showed no classical AQP5 + CK7 − acinar cell clusters (CK7 marks intercalated ducts, IDs). In contrast, the parenchyma was dominated by hybrid epithelial "structures" with ID-like morphology, containing a mixture of AQP5 + CK7 − , AQP5 − CK7 + , and AQP5 + CK7 + cells (30 structures/mm 2 ). These structures were present at lower frequencies in sicca control (2/mm 2 ) and pSS (10/mm 2 ) tissue. Hybrid structures contained proliferating (Ki67 + ) cells and senescent (p16 + ) cells. Striated ducts showed no abnormal morphology post PD-L1 treatment, in contrast to pSS tissue. PD-L1 expression was detected in the SG parenchyma following anti-PD-L1 therapy. The SG post-PD-L1 therapy further demonstrated focal lymphocytic sialadentitis, harboring disperse, and focal CD4 + T cell-rich infiltrates. CD8 + T cells were also present. In this patient, these CD4 + and CD8 + T cells were observed in-between and inside hybrid structures. CD20 + B-cells were infrequently detected following PD-L1 blockade, in contrast to their preponderance in pSS SG tissue.Conclusion: This patient lacked conventional SG acinar cells following anti-PD-L1 therapy and demonstrated presence of hybrid intercalated duct-like structures.Pringle et al. Lack of Acinar Cells With Anti-PD-L1 TherapyUnderstanding which mechanisms and dynamics underpinning this aberrant parenchyma may be crucial to understand how SG dysfunction post ICI therapy, and potentially other affected organs. Furthermore, although the patient treated with anti-PD-L1 antibody examined here fulfills the criteria for pSS and demonstrated focal lymphocytic sialadentitis, the further histopathological characteristics do not resemble pSS.

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Section: Lack Of Conventional Acinar Cells and Skewing Of The Epithelsupporting

confidence: 88%

Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor

et al. 2020

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“…AQP5 has been described to serve a role in several diseases associated with dysfunction of water regulation, and is key in this process (10–12). Furthermore, differences in the cellular location and mRNA expression pattern of AQP5 were observed in the nasal tissues from CRS patients compared with those of healthy controls (13,14).…”

Section: Introductionmentioning

confidence: 99%

Effects of glucocorticoid on the expression and regulation of aquaporin 5 in the paranasal sinus of rats with chronic rhinosinusitis

Cui

Lü

et al. 2017

Experimental and Therapeutic Medicine

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Aquaporins (AQPs) are water-specific membrane channel proteins that regulate water homeostasis for cells and organisms. AQP5 serves an important role in the maintenance of mucosal water homeostasis, and potentially contributes to mucosal edema and inflammation formation in chronic rhinosinusitis (CRS). The aim of the present study was to explore the expression pattern of AQP5 and the effect of glucocorticoids on AQP5 expression in rats with CRS. The rats were randomly divided into three equal groups, as follows: CRS, dexamethasone (dexa) treatment and control groups. A polyvinyl acetal material containing Staphylococcus aureus was inserted into the left nasal cavity of each rat from the CRS and dexa groups. On the 90th post-operative day, the dexa group received dexamethasone (2 mg/kg/day) via intraperitoneal injection for 7 days. The controls did not receive any treatment. The expression of AQP5 in the sinonasal mucosa was determined using immunohistochemistry and quantitative PCR. The immunoreactivities of AQP5 were primarily noted in the epithelial lining and glandular cells, the vascular endothelium and in the goblet cells in the sinonasal mucosa. The AQP5 mRNA expression level was significantly higher in the dexa group than in the control and CRS groups (P=0.006 and P=0.014, respectively). However, no significant difference was indicated between the CRS and control groups (P=0.760). In conclusion, the current study suggests that glucocorticoids induce AQP5 expression in the sinonasal mucosa of CRS rats, which highlights AQP5 as a potential target in the diagnosis and treatment of CRS.

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“…Apart from this, a number of factors preclude a comparison of the studies, including population differences (Patel & Shahane, 2014). In addition, changes in the microenvironment of oral cavity resulting from salivary hypersecretion have been shown to influence the microbiome (Bhattarai, Junjappa, Handigund, Kim, & Chae, 2018;Yoshimura et al, 2016).…”

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confidence: 99%

Saliva microbiome in primary Sjögren’s syndrome reveals distinct set of disease‐associated microbes

et al. 2020

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Objective This study systematically aims to evaluate the salivary microbiome in patients with primary Sjögren's syndrome (pSS) using 16S rRNA sequencing approach. Methods DNA isolation and 16S rRNA sequencing was performed on saliva of 37 pSS and 35 control (CC) samples on HiSeq 2500 platform. 16S rRNA sequence analysis was performed independently using two popular computational pipelines, QIIME and less operational taxonomic units scripts (LoTuS). Results There were no significant changes in the alpha diversity between saliva of patients and controls. However, four genera including Bifidobacterium, Lactobacillus, Dialister and Leptotrichia were found to be differential between the two sets, and common between both QIIME and LoTuS analysis pipelines (Fold change of 2 and p < .05). Bifidobacterium, Dialister and Lactobacillus were found to be enriched, while Leptotrichia was significantly depleted in pSS compared to the controls. Exploration of microbial diversity measures (Chao1, observed species and Shannon index) revealed a significant increase in the diversity in patients with renal tubular acidosis. An opposite trend was noted, with depletion of diversity in patients with steroids. Conclusion Our analysis suggests that while no significant changes in the diversity of the salivary microbiome could be observed in Sjögren's syndrome compared to the controls, a set of four genera were significantly and consistently differential in the saliva of patients with pSS. Additionally, a difference in alpha diversity in patients with renal tubular acidosis and those on steroids was observed.

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Abnormal distribution of AQP5 in labial salivary glands is associated with poor saliva secretion in patients with Sjögren's syndrome including neuromyelitis optica complicated patients

Abstract: Our results suggest that AQP5 but not AQP4 contributes to salivary secretion in patients with SS including those with NMO complicated with SS.

Cited by 41 publications

References 31 publications

Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor

Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor

Effects of glucocorticoid on the expression and regulation of aquaporin 5 in the paranasal sinus of rats with chronic rhinosinusitis

Saliva microbiome in primary Sjögren’s syndrome reveals distinct set of disease‐associated microbes

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