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Abstract：
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.
摘要：
在没有乙型肝炎病毒（HBV）合并感染的情况下，已在Sjögren病（SjD）患者的小唾液腺（MSG）组织中检测到丁型肝炎病毒（HDV）。先前的研究表明，HDV抗原（HDAg）的表达可以在体内引发SjD样表型，展示潜在的因果关系。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。这项回顾性研究在2014年至2021年之间收集的48个SjDMSG样本中对HDV进行了表征。HDAg表达的分析，包括细胞类型和亚细胞定位，HDVRNA的原位杂交，并与相关的SjD和病毒性肝炎临床特征进行比较分析，进行了。在味精腺泡中检测到HDAg，导管,肌上皮，脂肪细胞和细胞核，细胞质，和线粒体.原位杂交检测到HDV基因组RNA在MSG细胞核中的定位。HDAg强度与局灶性淋巴细胞炎症之间以及抗SSA/Ro-52和抗SSA/Ro-60患者之间均存在显着的负相关。在分析自身免疫性疾病与SjD的合并症时，研究发现,与阴性和中等HDAg强度组相比,高HDAg强度组诊断为自身免疫性甲状腺炎和/或甲状腺功能减退症的SjD患者明显更多.在MSG定位的HDAg和肝酶或明显的HBV合并感染之间没有检测到显着的关联。这项研究进一步证实，在第三个独立的SjD患者队列中，SjD受影响的唾液腺组织中存在慢性HDV持久性的非肝性储库。此外,这项研究描述了HDAg与线粒体的独特共定位。在受SjD影响的唾液腺组织中检测HDV抗原和序列，在没有明显的当前或过去的HBV合并感染的情况下，需要进一步调查。
