Home > published mauscripts of interest > Basic research on Sjögren’s Syndrome continues, also in the Netherlands

Basic research on Sjögren’s Syndrome continues, also in the Netherlands

A recently published thesis by Nienke Roescher from the University of Amsterdam further contributes to the difficult and ongoing search on how to tackle the disease Sjögrenś sydnrome. Although as a rheumatologist I am more into clinical research, the evolving knowledge obtained from basic (laboratory) research is of invaluable importance in guiding the way to find a cure for this disease.

Nienke Roescher concluded her thesis as follows:

The research presented herein summarizes the current knowledge on cytokines and their presence in SS, it identifies immunological targets in mice with an SS-like disease and shows that local gene therapy can be successful for the treatment of the inflammatory salivary gland component of a SS-like disorder in mice. The chance for success of this approach depends on proper timing and should be aimed at the right target.

More specifically she described a novel cytokine protein called APRIL which seems to be less available in Sjögren’s syndrome then in the normal healthy population, it’s exact meaning and importance remains to be elucidated.

We found that APRIL is expressed at lower levels in the salivary glands of SS patients compared with healthy volunteers and sicca patients. At the same time some patients had strongly increased APRIL levels in the peripheral blood. BAFF was detected in the ductal cells and in infiltrating cells which confirms previous observations by other researchers. The receptors to which these two cytokines bind were also present in varying degrees when compared between patients and healthy people. These abnormalities indicate that a therapy inhibiting BAFF in the salivary gland may be beneficial, but local inhibition of APRIL may not be effective in the treatment of SS.

Furthermore she tested, using a gene therapeutical approach three different immunomodulating proteins (soluble ICAM-1 (sICAM-1), soluble T-cell co-stimulatory CD40 and transmembrane and CAML interactor receptor (TACI) of BAFF + a proliferation inducing ligand (APRIL), two cytokines involved in B cell stimulation) for their potential to resolve salivary gland inflammation as a form of gene therapy in a Sjögren-like mice model. Two of them actually lowered the inflammation (CD40 did not have an effect on inflammation), however did not consequently increase salivary flow. However the work of Nienke Roescher adds to the proof-of-concept i.e. the principle of successful local gene therapy.

Find the thesis of Nienke Roescher here online.

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