Sjögren's syndrome (SS) is a chronic autoimmune disorder that typically affects exocrine glands—mainly labial and lacrimal—leading to complaints of dry mouth and eyes. Given that periepithelial mononuclear cell infiltrates, both in exocrine glands and in other parenchymal organs (kidney, lung, and liver), are the histopathological disease hallmark, the term autoimmune epithelitis has been proposed. B cell hyperactivity is another cardinal SS feature manifested by the presence of autoantibodies and hypergammaglobulinemia, as well as clinical/serological phenotypes mediated by immune complexes, such as peripheral neuropathy, vasculitic lesions, and hypocomplementemia. These have been designated adverse predictors for lymphoma development in approximately 5% to 10% of patients. Activation of the type I interferon/B cell–activating factor axis in SS has recently attracted particular attention. Inappropriate overexpression of endogenous nucleic acids in a genetically susceptible individual might provide a plausible scenario for the immune activation observed in SS.

The heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome (SS) is well established. Several adverse clinical and laboratory predictors have been described. In the current work, we aimed to formulate a predictive score for NHL development, based on clinical, serological, and histopathological findings at the time of SS diagnosis. In the present case-control study of 381 primary SS patients and 92 primary SS patients with concomitant NHL, clinical, serological, and histopathological variables at the time of SS diagnosis were retrospectively recorded. For the identification of predictors for NHL development univariate and multivariate models were constructed. Salivary gland enlargement (SGE), lymphadenopathy, Raynaud phenomenon, anti-Ro/SSA or/and anti-La/SSB autoantibodies, rheumatoid factor (RF) positivity, monoclonal gammopathy, and C4 hypocomplementemia were shown to be independent predictors for NHL development. On the basis of the number of independent risk factors identified, a predictive risk score for NHL development was formulated. Thus, patients presenting with ≤2 risk factors had a 3.8% probability of NHL development, those with 3 to 6 risk factors 39.9% (OR (95%CI): 16.6 [6.5-42.5], P < 0.05), while in the presence of all 7 risk factors the corresponding probability reached 100% (OR [95%CI]: 210.0 [10.0-4412.9], P < 0.0001). In conclusion, an easy to use diagnostic scoring tool for NHL development in the context of SS is presented. This model is highly significant for the design of early therapeutic interventions in high risk SS patients for NHL development.