Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Autoimmunity. 2019 Nov-Dec;52(7-8):242-250. doi: 10.1080/08916934.2019.1684475. Epub 2019 Oct 30.
Salivary and lacrimal gland involvement is a characteristic feature of primary Sjögren's syndrome (pSS), where tissue destruction is mediated by mononuclear cell infiltration, resulting in lacrimal and salivary gland impairment. We have previously shown distinct prevalence of adipose tissue replacement in the minor salivary gland tissue from pSS patients. The salivary gland microenvironment was further examined through microarray analysis, identifying signalling pathways that promoted adipose tissue development, inflammation, and lymphoma. As B cells may also contribute to disease progression, we now aimed to study the B cell pattern with regard to adipocyte development in pSS. Double immunohistochemical staining of paraffin-embedded salivary gland tissue from 22 pSS patients and 11 non-SS tissue controls was employed, using the characteristic pSS autoantigens Ro52 or Ro60, alongside CD27. Additional CD138/CD20 double staining was also performed to identify the plasma- and general B- cell pattern. Our results demonstrated CD27-positive Ro52 and Ro60 specific cells observed within and in close proximity to the adipose tissue. CD138-positive plasma cells were also seen in areas of adipose tissue replacement, while the CD20 cells were located within focal infiltrates, forming distinct B cell zones. The quantification of CD138 and CD20 cells revealed elevated numbers of CD138 cells in areas of fatty infiltration, and also interstitially, in the salivary glands of pSS patients when compared to non-SS controls. A significant increase ( < .01) in CD138 cells close to areas of fatty infiltration, and interstitially, with increasing fatty infiltration and focus score was further observed in pSS patients. A correlation between the number of CD20 B cell zones/mm of salivary gland tissue and focus score values was also witnessed in the patients ( = 0.6047, < .001). In conclusion, autoantigen-specific B cells and plasma cells appear prominent in areas of fatty infiltration in salivary glands of pSS patients, where an increase in CD138 plasma cells and CD20 B cells, in relation to both fatty and focal infiltration, suggests their active involvement in promoting inflammation. Further studies are needed to assess whether these adipocytes are also a result of tissue repair.
唾液腺和泪腺受累是原发性干燥综合征 (pSS) 的特征性表现,组织破坏是由单核细胞浸润介导的,导致泪腺和唾液腺损伤。我们之前已经表明,在 pSS 患者的小唾液腺组织中,脂肪组织替代具有明显的不同的患病率。通过微阵列分析进一步研究了唾液腺微环境,确定了促进脂肪组织发育、炎症和淋巴瘤的信号通路。由于 B 细胞也可能促进疾病进展,我们现在旨在研究 pSS 中与脂肪细胞发育有关的 B 细胞模式。使用特征性的 pSS 自身抗原 Ro52 或 Ro60 以及 CD27,对 22 例 pSS 患者和 11 例非 SS 组织对照的石蜡包埋唾液腺组织进行双重免疫组织化学染色。还进行了额外的 CD138/CD20 双重染色,以识别浆细胞和一般 B 细胞模式。我们的结果表明,在脂肪组织内和附近观察到 CD27 阳性的 Ro52 和 Ro60 特异性细胞。在脂肪组织替代区域也观察到 CD138 阳性的浆细胞,而 CD20 细胞位于局灶性浸润区内,形成独特的 B 细胞区。CD138 和 CD20 细胞的定量分析显示,与非 SS 对照组相比,pSS 患者脂肪浸润区域和间质中的 CD138 细胞数量增加。在 pSS 患者中,还观察到脂肪浸润区域和间质中 CD138 细胞数量随着脂肪浸润和焦点评分的增加而显著增加(<0.01)。在患者中还观察到 CD20 B 细胞区/唾液腺组织 mm 数与焦点评分值之间的相关性(=0.6047,<0.001)。总之,自身抗原特异性 B 细胞和浆细胞在 pSS 患者的唾液腺脂肪浸润区域中显得突出,与脂肪和局灶浸润相关的 CD138 浆细胞和 CD20 B 细胞的增加表明它们积极参与促进炎症。需要进一步研究以评估这些脂肪细胞是否也是组织修复的结果。