School of Dentistry, University of Utah, Salt Lake City, UT, USA.
Department of Pathology, Microbiology and Immunology, University of Utah, Salt Lake City, UT, USA.
J Dent Res. 2023 Oct;102(11):1272-1279. doi: 10.1177/00220345231186394. Epub 2023 Aug 14.
Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren's disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.
δ 型肝炎病毒（HDV）已在干燥综合征（SjD）患者的小唾液腺（MSG）组织中检测到，而无乙型肝炎病毒（HBV）合并感染。先前的研究表明，HDV 抗原（HDAg）的表达可在体内引发 SjD 样表型，表明存在潜在的因果关系。我们假设如果 HDV 在 SjD 的发展中起作用，那么 HDV 谱可能与疾病表现相关。本回顾性研究对 2014 年至 2021 年间收集的 48 例 SjD MSG 样本中的 HDV 进行了特征描述。进行了 HDAg 表达的分析，包括细胞类型和亚细胞定位、HDV RNA 的原位杂交以及与相关 SjD 和病毒性肝炎临床特征的比较分析。在 MSG 腺泡、导管、肌上皮和脂肪细胞中检测到 HDAg，并定位于细胞核、细胞质和线粒体。原位杂交检测到 MSG 细胞核中 HDV 基因组 RNA 的定位。在 SjD 患者中，HDAg 强度与局灶性淋巴细胞炎症呈显著负相关，并且在同时存在抗 SS-A/ Ro-52 和抗 SS-A/ Ro-60 的患者中也是如此。在分析 SjD 合并自身免疫性疾病时，发现与 SjD 相关的自身免疫性甲状腺炎和/或甲状腺功能减退症患者在高 HDAg 强度组中的比例明显高于阴性和中度 HDAg 强度组。在 SjD 患者的 MSG 定位 HDAg 与肝酶或明显的 HBV 合并感染之间未发现显著相关性。本研究进一步证实，在第三个独立的 SjD 患者队列中，在 SjD 相关的唾液腺组织中存在非肝脏的慢性 HDV 持续感染储库。此外，本研究描述了 HDAg 与线粒体的独特共定位。在 SjD 相关的唾液腺组织中检测到 HDV 抗原和序列，且无明显的当前或过去 HBV 合并感染，需要进一步研究。
