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Sjogren’s Syndrome

Sjogren’s syndrome is a worldwide disease. It affects all ages, although there can be differences in the presentation of the disease when it affects. We have a peak incidence around 40 and 50 years of age. And it is a predominantly female disorder with a ratio of female to male of 9:1.

Further on, Sjögren's syndrome is a broad spectrum of presentation, all from organ specific autoimmune exocrinopathy to systemic disease affecting several organs; kidneys, lungs and further on, dry eyes, dry mouth. So it’s not only a disease related to the exocrine glands, like lacrimal and salivary glands, although the major presentations most of the time are dry eyes and dry mouth as a predominant finding. But we should also recognize that we can have, in early stages of the disease, patients who have very mild dryness symptoms so we should recognize that as a particular presentation as well. Further on, it is very difficult many times in specifying, having the patient to specify the time when the disease started. Many times it is in relation to some infections.

We come to the first learning objectives where I actually will try to take you through what we know about autoantibodies. Try to learn how autoantibodies influence the pathophysiology of Sjogren’s syndrome. It is natural for us to start with an introduction about the autoantibodies where we have implications both for diagnosis as well as maybe also pathogenesis. The B cells are activated and that is a very consistent finding in Sjogren’s syndrome. We have loss of immune tolerance in the B cell compartment.

Lots of work has been done during the last year defining the specificity as well as the characterizing the target antibodies in Sjogren’s syndrome. The most important of these autoantibodies are anti-Ro anti-La.

Some basic features then, or some basic principles about this. It should be obtained through normal-appearing mucosa. The mucosa cannot be inflamed, it should not be affected by Candidiasis, for example. It should include 5-10 separate glands, and I think a lot of mistakes have been done here when they only sample one or two glands and that doesn’t make it enough for making the proper diagnosis. One has to exclude non-specific changes, and that includes fibrosis, also neuratrophy, dactyl hyperplasia, as well as fatty infiltration - and that’s quite common, actually, that you see those changes in glands. Those kind of areas should not be counted. We should demonstrate focal cell adenitis in all or most of these 5-10 separate glands. So it should be a spreading of inflammation and not very local. It should be a general phenomenon. The focal score can then be calculated and it should be .. we have a diagnostic threshold of more than 1 or similar to 1. There has been a debate on where this level should be set, but originally it was defined as more than 1, but the European criteria accepts 1 or more.

When making the diagnosis of Sjogren’s syndrome one can use this kind of algorithm, which is based on the EU criteria where we on top have the subjective symptoms, the ocular symptoms and the oral symptoms. But remember that we can have patients without subjective symptoms so it’s not an obligation that we should include this. We go further on down with various investigations to look for ocular signs. We define the keratoconjunctivitis sicca. If it’s positive, we go further on with histopathology, with labile biopsy and I think it’s a good sequence to start with the eye investigation.

IL-10, TNF alpha, interferon gamma. It’s predominance mainly of TH-2 cytokines. This has also been shown in peripheral blood recently that you have overproduction of IL-6 and IL-10, for example. Which probably could help or drive the autoantibody production in the patients.

So my final learning objective, or educational objective, will then be to try to understand the role of apeidosis in Sjogren’s syndrome. It starts with the shrinkage of the cells. We get some _ of the cell surface and here, we know for example, the autoantigens are expressed in high amounts, maybe enabling them to be presented to the immune system.

We will now be looking for polymorphs in the fascia because it was originally thought that this could be of interest as a potential candidate gene for Sjogren’s syndrome. Certainly _ would be of interest since it is one of the molecules that regulates apeidosis. One of the first molecules that is recognized actually. We have found one polymorphs when we compare to a patient have the control in the patients in healthy controls. This is of low significance so probably it is of no relevance. We have not been able to find any differences in the polymorphs or in the false ligand gene. So even here, as a potential candidate gene in Sjogren’s syndrome, there is nothing to get.

The summary then, the gland in hypofunction in Sjogren’s syndrome could of course be related to cell infiltration and that’s what we have been believing and what we have thought of all the time. Certainly, we have to keep in mind that Sjogren’s syndrome is an inflammatory and immunological disease, and autoimmune disease. Of course we can consider glandular destruction as one possibility, but I think more information will be obtained if we study this for the future. That we have an aberrant, immune mediated, neuro-hormonal event. Illustrated by the anti-muscarinic receptor with autoantibodies.