PhD ceremony Mr. R.P.E. Pollard: B cell targeting in Sjögren's syndrome. Clues to pathogenesis

PhD ceremony: Mr. R.P.E. Pollard

Dissertation: B cell targeting in Sjögren's syndrome. Clues to pathogenesis

Promotor(s): prof. A. Vissink, prof. F.G.M. Kroese, prof. F.K.L. Spijkervet

Faculty: Medical Sciences

Sjögren’s syndrome (SS) is an autoimmune disorder that is characterized by inflammatory infiltrates in the exocrine glands, particularly in the salivary and lacrimal glands. Most of the patients suffer from dry mouth and dry eyes. Other clinical manifestations such as fatigue, joint and muscle pain are often present. Along with the dryness complaints, these events lead to a reduced quality of life. A major complication of SS is the development of a malignant lymphoma in the salivary glands, mostly a mucosa associated lymphoid tissue (MALT) lymphoma.

There is no recognized causal treatment for SS. Recently, new treatment options are introduced in order to, through the use of antibodies, inhibit the disease activity and to prevent further progression. Rituximab, a monoclonal antibody directed against the protein CD20 on B cells, showed favorable results in several clinical studies. This research has focused on the immuno(histo-)logical effects of B-cell depletion by rituximab in patients with SS. My research shows that a treatment with rituximab leads to an improvement of the inflammatory process in the salivary gland. Furthermore, several additional therapeutic targets (BAFF, IL -6 ) are described in this thesis. In addition, a study how a patient with SS MALT lymphoma can be treated best is described. The study shows that in SS patients with MALT lymphoma, under certain conditions, a "watchful waiting" is justified.