Sjögren’s Disease is When the Immune System Chases Its Own Tail

Kittens are fascinatingly weird creatures. They sleep, jump, hunt ghosts, and are some of the cutest things in the world. They also occasionally chase their own tail. Some cats catch their tail, bite it, and enter a feedback loop in which they feel pain, and bite harder in response. This is similar to autoimmune disease, where the immune system mistakenly attacks the body’s own cells, senses dying cells as threats, and sends in more immune cells to investigate, worsening the situation.

Sjogren’s disease (also called Sjogren’s syndrome and pronounced “SHO-grens”) is a chronic, systemic autoimmune disease that causes dry eye, dry mouth, fatigue, and joint pain.^[1,2] Exact numbers are difficult to chase down because different classification criteria are used, but Sjogren’s is relatively common for an autoimmune disease, with about 3-5 new cases per 100,000 people per year.^[1] Onset of Sjogren’s disease usually occurs in a person’s 30s-40s and is 9-20 times more common in women than men.^[1,3] Sjogren’s can manifest on its own (Primary Sjogren’s) or be a result of another autoimmune disease like lupus or rheumatoid arthritis (Secondary Sjogren’s).^[1] 

Around 80% of those with Sjogren’s disease experience the symptoms mentioned above: dry eye, dry mouth, fatigue, and joint pain.^[2] For another 30-40% of patients, the disease scratches below the surface and affects the whole body, called systemic disease.^[2] Systemic problems can affect multiple organs and organ systems, including the kidneys, blood vessels, and nervous system.^[1,2] Additionally, those with Sjogren’s disease are at a 15-20 times increased risk of developing B-cell (non-Hodgkin’s) lymphoma, a type of blood cancer.^[2]

The basic problem with Sjogren’s is that immune cells attack the salivary gland cells near the eyes and mouth.^[1,3] Salivary gland cells produce tears and saliva, which explains the dry eye and dry mouth, but how is Sjogren’s disease similar to a tail-chasing kitten? The kitten needs three essential elements for its tail shenanigans:

• Genetic risks: orange and calico cats have the highest chance of being dumb as bricks
• Environmental triggers: parasites, skin irritation, or even just a wiggling tail
• Feedback loop: every time the cat gets close enough, the tail moves just out of reach!

The development of Sjogren’s disease needs the same three elements: genetic risks, environmental triggers, and a feedback loop.^[3,4]

For those with Sjogren’s disease, genetic risks increase the immune system's sensitivity and prime it for disruption.^[3,4] In general, this means the genes that control the immune system’s activation pathways make it more likely that immune B-cells, T-cells, and/or interferons attack things that are not dangerous (like a wiggly tail). Environmental triggers are hard to pounce down on, but may include viruses, chemicals, and female sex hormones.^[3,4] These triggers “activate” the gland cells, prompting them to release chemicals that signal “danger” and start an inflammatory response.^[3,4] Immune system white blood cells, including T-cells and B-cells, detect these chemical signals and rush into the glands cells.^[3] This starts the feedback loop, the immune cells cause damaging inflammation and release enormous amounts of dangerous proteins called autoantibodies that target the salivary gland cells, damaging or destroying them.^[3,4] As the gland cells become damaged, they release additional “danger” signals, and the process continues, chasing that tail over and over. In addition, the massive amounts of autoantibodies can “spill over” into the rest of the body, causing the systemic problems mentioned above. The constant activation of B immune cells is thought to be the reason for the increased chance of B-cell (non-Hodgkin’s) lymphoma.^[3]

Kittens grow up and (usually) grow out of chasing their own tail, but the outlook hasn’t been so rosy for those with Sjogren’s disease. There are currently no FDA-approved disease-modifying medications for Sjogren’s disease. Many sufferers use over-the-counter or prescription treatments, like pilocarpine eye drops or oral solutions, to provide relief from their symptoms.^[2] Luckily, the cat’s out of the bag and there are several clinical trials investigating disease-modifying treatments for Sjogren’s disease; things that can stop the disease from progressing. These trials target the immune system itself or specific parts of it to try to slow damage to salivary gland cells, limit the white blood cell responses, or lower the number of autoantibodies produced by immune cells.^[3,5] With the help of researchers and volunteers, those with Sjogren’s may be able to stop chasing their tail and lie down for a well-deserved catnap.

Creative Director Benton Lowey-Ball, MWC, BS, BFA

References:

[1] Patel R, Shahane A. The epidemiology of Sjögren’s syndrome. Clinical epidemiology. 2014 Jul 30:247-55. https://doi.org/10.2147/clep.s47399

[2] Mariette X, Criswell LA. Primary Sjögren’s syndrome. New England Journal of Medicine. 2018 Mar 8;378(10):931-9. https://doi.org/10.1056/NEJMcp1702514

[4] Stefanski AL, Tomiak C, Pleyer U, Dietrich T, Burmester GR, Dörner T. The diagnosis and treatment of Sjögren’s syndrome. Deutsches Ärzteblatt International. 2017 May 26;114(20):354.https://doi.org/10.3238/arztebl.2017.0354

[3] Baldini C, Fulvio G, La Rocca G, Ferro F. Update on the pathophysiology and treatment of primary Sjögren syndrome. Nature Reviews Rheumatology. 2024 Aug;20(8):473-91. https://doi.org/10.1038/s41584-024-01135-3

[5] Yang Y, Shen Z, Shi F, Wang F, Wen N. Efgartigimod as a novel FcRn inhibitor for autoimmune disease. Neurological Sciences. 2024 Sep;45(9):4229-41. https://link.springer.com/article/10.1007/s10072-024-07460-5