Background/Purpose: Pro-inflammatory P2X7-receptor has been recently implicated in the pathogenesis of primary Sjögren’s syndrome (pSS), suggesting that it may be involved in the initiation and amplification of the innate immune response in salivary glands. In particular, previous studies have shown that the expression of P2X7R message in minor salivary glands was significantly higher in patients with positive anti-Ro-SSA and that it correlated with the minor salivary gland biopsy focus score. To date, however, no data are available on the role of the complex P2X7 receptor-inflammasome in the prognostic stratification of patients with pSS, specifically concerning their risk for lymphoma. The aim of this study was, therefore, to explore any eventual association or correlation between P2x7 mRNA levels in pSS minor salivary glands and in blood peripheral lymphocytes and traditional histological and serological risk factors for lymphoma in pSS. 

Methods: Consecutive, unselected patients with a diagnosis of pSS made according to the AECG 2002 were enrolled in this study. All subjects had a standardized evaluation for pSS which included oral and ophthalmologic examinations, laboratory testing and a rheumatologic evaluation. Mononuclear cells were isolated from fresh blood by density gradient centrifugation. Total RNA was extracted from the frozen salivary gland tissue and from the frozen pellet of lymphocytes and expression of the P2X7R mRNA was determined by real-time PCR. Minor salivary gland biopsies were re-evaluated by light microscopy in order to identify GC-like structures. For statistical comparisons, non parametric Mann-Whitney test and Spearman’s rank correlation coefficient were employed. 

Results: Twenty pSS subjects were enrolled in the study. At diagnosis, 20% of pSS patients had GC-like structures in their salivary glands. P2X7R mRNA expression was significantly higher in the salivary glands of pSS with GC-like structures than in those without GC-like structures and correlated significantly with minor salivary gland focus score (r=0.688, p=0.000), beta-2 microglobulin levels (r=0.538, p=0.02) and  IgG levels (r=0.452, p=0.02). Moreover, P2X7R mRNA salivary expression levels were significantly higher in patients with clinically evident major salivary glands enlargement and/or disease specific parenchyma dyshomogeneity documented by salivary gland ultrasonography. No significative correlations were found between P2X7R expression in peripheral lymphomonocytes and all the histological and laboratory risk factors for lymphoma examined in the study.

Conclusion: The results of this proof of concept study reinforce the potential involvement of the salivary P2X7R in pSS chronic salivary inflammation which have consistently been associated with an increased risk of malignant lymphomas. Further investigation are mandatory to clarify whether salivary P2X7R expression might be useful to identify pSS patients at lymphoma risk.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prognostic-value-of-the-complex-p2x7-receptor-inflammasome-in-patients-with-primary-sjogrens-syndrome-at-lymphoma-risk/