<scp>E</scp>pstein‐<scp>B</scp>arr virus in the enlarged salivary tissues of patients with <scp>I</scp>g<scp>G</scp>4‐related disease

Furukawa, Takatoshi; Shimotai, Yoshitaka; Ohta, Nobuo; Ishida, Akihiro; Kurakami, Kazuya; Suzuki, Hitoshi; Yamakawa, Mitsunori; Hongō, Seiji; Kakehata, Seiji

doi:10.1002/lary.25153

Cited by 4 publications

(8 citation statements)

References 21 publications

(84 reference statements)

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“…The GO and KEGG analyses of B cells and T cells in SMGs and peripheral blood showed that the infection-related pathway and ‘antigen binding’ pathway were shared, which is consistent with previous findings 42. It has been reported in the literature that increased numbers of EBV-infected cells were observed in IgG4-related lymphadenopathy, and EBV-associated molecules were overexpressed in the affected salivary glands of IgG4-RD 43 44. This suggests that infection may be a trigger for IgG4-RD.…”

Section: Discussionsupporting

confidence: 89%

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Wang

Feng

et al. 2023

Ann Rheum Dis

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ObjectivesThe aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD.MethodsWe performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results.ResultsWe identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD.TOP2A_B cells andTOP2A_T cells had stemness signatures, and trajectory analysis showed thatTOP2A_B cells may differentiate into IgG4+plasma cells and thatTOP2A_T cells may differentiate into T follicular helper (Tfh) cells.ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD.ConclusionOur data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

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Section: Discussionsupporting

confidence: 89%

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Wang

Feng

et al. 2023

Ann Rheum Dis

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“…Malignancies in patients with IgG4-related diseases in head and neck regions were lymphoma and salivary duct carcinoma in present study. It is well known that chronic persis- tent inflammation can induce B cell activation and mucosa associated lymphoid tissue lymphoma (Furukawa et al 2015). In Sjögren syndrome, antigenic activation of B cells, together with oncogenic events, including p53 inactivation and bcl-2 activation, may play important roles in B cell monoclonal proliferation and malignant transformation (Ohta et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…IgG, IgG4, CD20, CD79a and cytokeratin (CK) were immunohistochemically examined by using a labeled streptavidinbiotin-complex method as described previously (Kamisawa et al 2015, Furukawa et al 2015. In brief, 10-μm sections were taken from paraffin-embedded tissue blocks and then deparaffinized and rehydrated.…”

Section: Methodsmentioning

confidence: 99%

“…The underlying mechanism of IgG4-RD involves predominance of T helper (Th) 1 and T cytotoxic type (Tc) 1 cells, overexpression of IL-17, tumor growth factor (TGF)-β, and periostin in the affected site(s) in persistent chronic inflammation (Ohta et al 2012a(Ohta et al , b, 2013. Recent studies have also suggested that Epstein-Barr virus might play an important role in pathogenesis of IgG4-RD (Furukawa et al 2015). However, the mechanism responsible for the onset and systemic involvement of IgG4-RD still remains a mystery.…”

Section: Introductionmentioning

confidence: 99%

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Malignancies in Patients with IgG4-Related Diseases in Head and Neck Regions

Ikeda

Kurakami

Ohta

et al. 2019

Tohoku J. Exp. Med.

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Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease, characterized by high serum IgG4 concentrations and IgG4-producing plasma cell expansion with fibrotic or sclerotic changes in affected organs. Recent work has focused on the relationship between IgG4-RD and malignancies, but there is no report of malignancies associated with IgG4-RD in head and neck regions. The aim of this study was to analyze the clinicopathological characteristics of malignancies in patients with IgG4-RD in head and neck regions. We retrospectively analyzed 26 patients with IgG4-RD (12 men and 14 women aged 60.6 ± 11.6 years). The mean follow-up period was 26.6 months (from 12 to 96 months). These patients were divided into single-lesion group (n = 12) with IgG4-RD only in head and neck regions and multiple-lesion group (n = 14) with IgG4-RD in other regions. There was no significant difference in serum IgG4 concentrations between the single-lesion group (459.4 ± 336.4 mg/dL) and the multiple-lesion group (908.0 ± 739.2 mg/dL) (P = 0.07), whereas the IgG4/IgG ratio was significantly lower in the single-lesion group (22.8 ± 11.0%; n = 11) compared with the multiple-lesion group (31.7 ± 15.0%; n = 11, P = 0.02). Among the 26 patients, two patients (7.7%), both in the multiple-lesion group, developed life-threatening malignancies (salivary duct carcinoma in the submandibular gland and lymphoma in the orbital tissue). All physicians need to keep in mind the possible coexistence of malignancies in patients with IgG4-RD with high IgG4/IgG ratio and multiple lesions at the time of diagnosis.

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“…Human herpes virus (HHV) −6B and −7 persist in the salivary glands [ 18 , 19 ] and are secreted in saliva [ 20 ]. The association between IgG4-positive sialadenitis and Epstein-Barr virus (EBV) has been investigated in a few small cohorts [ 21 , 22 ], but evidence supporting this is still deficient. Human parvovirus B19 (B19V) has a high seroprevalence (40–80%) among adults, and has been reported to persist in multiple tissues, including the tonsils [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Viral DNA in submandibular gland tissue with an inflammatory disorder

Keski-Säntti,

Waltimo,

Mäkitie

et al. 2024

Journal of Oral Microbiology

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Background The etiology behind different types of chronic sialadenitis (CS), some of which exhibit IgG4 overexpression, is unknown. Further, IgG4-related disease (IgG4-RD) commonly affects the submandibular gland, but its relationship to IgG4-overexpressing CS, and the antigen triggering IgG4 overexpression, remain unknown. Materials and Methods By qPCR, we assessed the presence of 21 DNA-viruses causing IgG4 overexpression in submandibular gland tissue from patients with IgG4-positive and IgG4-negative CS. Healthy submandibular glands and glands with sialolithiasis without CS were used as controls. We examined the distribution of HHV-7, HHV-6B and B19V DNA, within virus PCR-positive tissues with RNAscope in-situ hybridization (RISH). Results We detected DNA from seven viruses in 48/61 samples. EBV DNA was more prevalent within the IgG4-positive samples (6/29; 21%) than the IgG4-negative ones (1/19; 5.3%). B19V DNA was more prevalent within the IgG4-negative samples (5/19; 26%) than the IgG4-positive ones (4/29; 14%). The differences in virus prevalence were not statistically significant. Of the IgG4-RD samples ( n = 3) one contained HHV-6B DNA. RISH only showed signals of HHV-7. Conclusions None of the studied viruses are implicated as triggering IgG4-overexpression in CS. Although our results do not confirm viral etiology in the examined conditions, they provide valuable information on the prevalence of viruses in both diseased and healthy submandibular gland tissue.

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Epstein‐Barr virus in the enlarged salivary tissues of patients with IgG4‐related disease

Abstract: 4.

Cited by 4 publications

References 21 publications

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Malignancies in Patients with IgG4-Related Diseases in Head and Neck Regions

Viral DNA in submandibular gland tissue with an inflammatory disorder

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