Sclerosing Sialadenitis Is Associated With Salivary Gland Hypofunction and a Unique Gene Expression Profile in Sjögren's Syndrome.

To develop a novel method to quantify the amount of fibrosis in the salivary gland and to investigate the relationship between fibrosis and specific symptoms associated with Sjögren's syndrome (SS) using this method. Paraffin-embedded labial salivary gland (LSG) slides from 20 female SS patients and their clinical and LSG pathology data were obtained from the Sjögren's International Collaborative Clinical Alliance. Relative interstitial fibrosis area (RIFA) in Masson's trichrome-stained LSG sections was quantified from digitally scanned slides and used for correlation analysis. Gene expression levels were assessed by microarray analysis. Core promoter accessibility for RIFA-correlated genes was determined using DNase I hypersensitive sites sequencing analysis. RIFA was significantly correlated with unstimulated whole saliva flow rate in SS patients. Sixteen genes were significantly and positively correlated with RIFA. In a separate analysis, a group of differentially expressed genes was identified by comparing severe and moderate fibrosis groups. This combined set of genes was distinct from differentially expressed genes identified in lung epithelium from idiopathic pulmonary fibrosis patients compared with controls. Single-cell RNA sequencing analysis of salivary glands suggested most of the RIFA-correlated genes are expressed by fibroblasts in the gland and are in a permissive chromatin state. RIFA quantification is a novel method for assessing interstitial fibrosis and the impact of fibrosis on SS symptoms. Loss of gland function may be associated with salivary gland fibrosis, which is likely to be driven by a unique set of genes that are mainly expressed by fibroblasts.

Yin H ，Pranzatelli TJF ，French BN ，Zhang N ，Warner BM ，Chiorini JA ，NIDCD/NIDCR Genomics and Computational Biology Core ... -  《Frontiers in Immunology》

Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjögren's syndrome among 1,726 registry participants.

To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sjögren's syndrome (SS). The database of the Sjögren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features. LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of ≥1 per 4 mm²) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of ≥1 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of ≥1 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of ≥1 than were those with a higher flow rate, after controlling for other phenotypic features of SS. Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of ≥1 per 4 mm², as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.

Daniels TE ，Cox D ，Shiboski CH ，Schiødt M ，Wu A ，Lanfranchi H ，Umehara H ，Zhao Y ，Challacombe S ，Lam MY ，De Souza Y ，Schiødt J ，Holm H ，Bisio PA ，Gandolfo MS ，Sawaki T ，Li M ，Zhang W ，Varghese-Jacob B ，Ibsen P ，Keszler A ，Kurose N ，Nojima T ，Odell E ，Criswell LA ，Jordan R ，Greenspan JS ，Sjögren's International Collaborative Clinical Alliance Research Groups ... -  《-》

[Biopsy of the minor salivary glands in the differential diagnosis of Sjögren's syndrome and chronic sialadenitis].

Afanas'ev VV ，Vinogradov VI 《TERAPEVTICHESKII ARKHIV》

Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren's syndrome?

Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement.

Zabotti A ，Zandonella Callegher S ，Lorenzon M ，Pegolo E ，Scott CA ，Tel A ，Giovannini I ，Robiony M ，Di Loreto C ，Zuiani C ，De Vita S ... -  《-》

Fibroblast markers in labial salivary gland biopsies in progressive systemic sclerosis.

Janin A ，Konttinen YT ，Grönblad M ，Karhunen P ，Gosset D ，Malmström M ... -  《-》