Viral DNA in submandibular gland tissue with an inflammatory disorder

Abstract

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.

Keywords: Chronic sialadenitis; DNA viruses; Polymerase chain reaction; Sialolithiasis; immunoglobulin G4 related disease.

Figure 1.

RNAscope ™ 2.0 HD Red on salivary gland FFPE samples. a, RISH with the technical positive PPIB probe control. b, RISH with the technical negative DapB probe control. c–e, RISH with the HHV-7 U4 probe on a HHV-7 qPCR-negative sample (C) and HHV-7 qPCR-positive sample from a patient with IgG4-positive CSS (D, E). Positive signals are presented as red punctuated dots. Original magnification × 40. Abbreviations: FFPE, formalin-fixed paraffin-embedded; HHV-7, human herpesvirus 7; PCR, polymerase chain reaction; CSS, chronic sclerosing sialadenitis.