Sjogren's syndrome introduction

Question 1

What is sjogren’s syndrome?

Answer 1

It is the second most common autoimmune rheumatic disease. It is chronic inflammation of exocrine glands, particularly salivary. It affects mostly women. Sjögren’s syndrome really impacts quality of life.

Question 2

What are symptoms of sjogren’s syndrome?

Answer 2

• Dryness of mouth and eyes it affects swallowing, talking and electronic uses
• Swelling of salivary glands
• Systemic effects like rashes
• joint pain
• presence of autoantibodies
• pins and needles sensation

Question 3

Immune cell infiltration in salivary glands?

Answer 3

When you look at infiltration of lymphocytes in salivary glands of patients with Sjögren’s syndrome, mild lesions have predominantly T cell infiltration while severe lesions there is higher B cell infiltration. In severe lesions there is organisation between T and B cell sites and regions with germinal centre like formations which support production of autoantibodies, tertiary lymphoid structures (Voulgarelis 2010)

Question 4

How to diagnose sjogren’s syndrome?

Answer 4

• Positive biopsy
• Anti-Ro antibodies
• Ocular staining

Question 5

Is Sjögren’s syndrome connected to other autoimmune diseases?

Answer 5

• SLE
• RA
• Thyroid autoimmunity

Question 6

What mouse model is good for studying sjogren’s syndrome?

Answer 6

NOD-SCID mouse model. They don’t have functioning immune system but they have changes in salivary glands

Question 7

Pathogenesis of Sjogrens syndrome?

Answer 7

1. Potentially EBV disturbing epithelium of salivary glands
2. Dysregulated epithelium produces chemokines
3. Chemokines lead to infiltration of lymphocytes
4. Lymphocytes interact with epithelium and further produce cytokines leading to attraction of plasmacytoid DCs (pDCs)
5. pDCs produce type 1 interferons which leads to production of BAFF
6. BAFF leads to activation and survival of B cells
7. This leads to Sjogrens syndrome
   (Voulgarelis 2010)

Question 8

What are anti-Ro antibodies?

Answer 8

They are present in Sjögren’s syndrome. They are antibodies that bind RNA binding proteins, leading to immune complexes containing antibody, protein and small RNAs. These are taken up by pDCs (this stimulates both Fc receptors and TLRs and gives very strong stimulus to produce type 1 interferons)

Question 9

Type 1 interferons in Sjogrens syndrome?

Answer 9

• Unregulated in Sjogrens
• Type 1 interferon pathway polymorphism associated with sjogrens
• IFN correlates with anti-RO levels
• There is an increase in pDCs in salivary glands but decreased peripheral blood. pDCs produce type 1 interferons

Question 10

Sjögren’s syndrome and B cell lymphoma?

Answer 10

A lot of Sjögren’s syndrome patients will develop B cell lymphoma. Likely due to EBV and B cells involvement.