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Objective: This study aims to determine the prevalence and risk factors associated with lymphoma in primary Sjögren's syndrome (pSS)., Methods: We conducted a cross-sectional study on pSS patients who were registered into the Integrated Data Repository (IDR) at the University of Florida (UF) Health Shands Hospital. The parameters, such as age, sex, race, and smoking status, were included. Lymphoma types in pSS were categorized. The clinical and laboratory features were compared between pSS patients with and those without lymphoma by utilizing the items in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)., Results: Among 1,211,343 patients, we found 6799 patients (0.56%) with lymphomas and 2562 patients (0.21%) with pSS. Out of the 2562 pSS patients, 67 patients (2.6%) were diagnosed with lymphoma. The difference in the clinical and laboratory features listed under the ESSDAI domains between pSS patients with lymphomas and pSS without it was significant (p < 0.05 or 0.01): fever, weight loss, lymphadenopathy, splenomegaly, lacrimal gland diseases, cough, shortness of breath, hematuria, cerebrovascular accident diseases, peripheral nerve involvement due to vasculitis, neutropenia, and thrombocytopenia., Conclusion: We report 2.6% of lymphoma prevalence in pSS, lower than previously reported in the literature., (© 2022 Wiley Periodicals LLC.)

Objectives: To elucidate the clinical values of anti-M3R in Sjögren's syndrome (SS) in the largest cohort for an anti-M3R study., Methods: The plasma of 361 subjects (156 primary SS [pSS], 62 non-SS-sicca [SICCA], 40 systemic lupus erythematosus [SLE], 50 rheumatoid arthritis [RA], and 53 healthy controls [HC]) was screened using our modified On-Cell-Western assay. Saliva from pSS (n=37) compared to SICCA (n=26) was also analysed. The sensitivity and specificity of anti-M3R and its association with comprehensive clinical and laboratory features were determined., Results: Plasma-anti-M3R was higher in pSS compared to other groups, differentiating pSS with good-to-excellent diagnostic power with a specificity of 85% and a sensitivity between 75% and 98%. pSS plasma-anti-M3R was positively correlated with ocular staining scores, anti-Ro/SSA, IgG, β2-microglobulin, ESR, and ESSDAI. It was negatively correlated with WBC, C4, and salivary scintigraphic indices. Saliva-anti-M3R was 3.59 times higher in pSS than in SICCA. Interestingly, the agreement between the 2002 American European Consensus Group criteria and the criteria substituted with plasma-anti-M3R for the lip biopsy reached 92%, with a significant kappa of 0.824., Conclusions: Anti-M3R enhances sensitivity and specificity for SS diagnosis, correlating with ocular dryness and glandular hypofunction, and the haematological/biological domains of the ESSDAI. Our findings also highlight the clinical significance of anti-M3R in SS diagnosis, especially where clinical assessments, such as lip biopsy, sialometry, or ocular evaluation, by multi-disciplinary specialists are limited.

Severe dry mouth in patients with Sjögren's Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries. [ABSTRACT FROM AUTHOR]