Determinants of disease severity in primary Sjögren’s syndrome

Abstract

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease primarily targeting salivary and lacrimal glands, leading to dryness of predominantly eyes and mouth. Additionally, inflammation of other organs is seen, like arthritis and skin lesions. The risk of B cell lymphoma is increased in pSS patients: approximately 3 – 11% of pSS patient will be affected, which is 15 – 18x higher than the risk seen in the general population.

This retrospective research performed in the UMC Utrecht (195 patients) and St. Antonius Hospital Nieuwegein (65 patients) focusses on the prediction of disease severity by using clinical manifestations and diagnostic tests like presence of auto-antibodies and salivary gland histology.

Most importantly, the results of salivary gland histology can be used to estimate prognosis. Patients with ≥3 clusters of lymphocytes per 4 mm2 in the biopsy specimen develop lymphoma in 14% of patients, whereas of patients with less clusters 98% will NOT develop lymphoma. Furthermore, patients with more inflammatory clusters and/or a diversity of auto-antibodies (≥3 of ANA, rheumatoid factor, anti-SSA and anti-SSB antibodies) have a higher risk of developing inflammation in other organs. New occurrence of certain symptoms is associated with the presence of lymphoma in a percentage of patients: vasculitis of skin (purpura) in 16%, peripheral neuropathy in 24%, glomerulonephritis in 100% and IgM-kappa paraprotein in 64% of cases. The presence of inflammatory manifestations is important for decisions regarding lymphoma treatment.

The EULAR Sjögren’s Syndrome disease activity index (ESSDAI) is a novel European score to assess disease activity which has not been tested in clinical practice, yet. Retrospectively applied to patient charts, mean ESSDAI scores are low and stable in the general pSS population, but individual changes in disease activity are well captured. Questions remain whether the scores in certain domains, e.g. pulmonary and muscular domains, are a good representative for disease severity. Since ESSDAI only scores new or worsening manifestations, calculating a cumulative ESSDAI score was proposed to describe the severity of the pSS disease course.

Interleukin-7 (IL-7) plays a critical role in the immunopathologic pathways in pSS, and IL-7 levels correlate to the extent of local and systemic disease. In a cohort of 41 pSS patients soluble IL7 receptor (sIL7r) levels were significantly increased, compared to age-matched controls. Additionally, levels of sIL7r were significantly higher in patients with systemic disease during 10 year follow-up. The additive value of sIL7r as biomarker has to be further studied in a larger cohort.

In conclusion, several clinical, laboratory and histologic markers can be used to estimate disease prognosis of pSS patients.