Cryopyrin+Associated+Periodic+Syndrome+(CAPS)

By: Matt Connolly

Fact Sheet
 * Name of disease ** : Cryopyrin Associated Periodic Syndrome (CAPS)


 * Root cause of disease ** : CAPS disease is caused by a mutation in the NLRP-3 gene. The mutation in this gene causes altercations in the protein cryopyrin that it encodes for. Cryopyrin is active in circulating infection fighting white blood cells. Cryopyrin also controls the production of another protein called interleukin-1 beta (IL-1 b ). IL-1 b is part of the immune system, so it circulates throughout the body and can trigger inflammation. Researchers have shown that mutations to the NLRP-3 gene can cause cryopyrin to produce too much IL-1 b . However, mutations t the NLRP-3 gene has only been found in about 50% of patients with CAPS. It is believed that additional mutations may exist, but they have not been discovered [1]. ** Affected cell types ** : The cells that are affected by this disease are mostly immune cells because they are the cells producing the mutant cryopyrin. The mutant cryopyrin then signals for the production of too much IL-1 b m, which can cause serious inflammation anywhere in the body if trigger. Therefore CAPS can affect any cell in the bo dy where the inflammation is triggered as it can damage any organ or area. The inflammation also causes neurons to fire [3].
 * Figure 1: ** A flow diagram of how someone becomes infected by CAPS, how the disease works, and how it is passed on.


 * Historical background ** : The first mutation in a gene responsible for an autoinflammatory disease (AID) was discovered in 1997. This mutation was responsible for the familial Mediterranean fever disease. Soon after this several other gene mutations responsible for AIDs were identified. The mutation in the NLRP-3 gene that causes CAPS was discovered and published in a paper by H. Hoffman et al. in 2001. The gene was first linked to a subtype of CAPS called FCAS, but was then linked to the other two subtypes, MWS and NOMID. Since the discovery of NLRP-3 these three subtypes have been clumped together as a continuum called CAPS. I was not able to find any famous people of historical events linked to CAPS, but that is probably because it was only recently diagnosed in 2001 [3].


 * Common symptoms ** : CAPS is an autoinflammatory disease, meaning that it is characterized by an inflammatory reaction that is unprovoked. With this disease recurrent episodes occur and the signs and symptoms vary by patient and in each episode. The most common symptoms of CAPS disease include rash, fever/chills, joint pain, fatigue, and eye redness/pain. The most severe form of CAPS can cause hearing and vision loss, mental impairment, significant bone deformities, or kidney failure. Symptom outbreaks can be triggered by cooling temperatures, stress, exercise, or unknown causes [1].


 * Standard treatments ** : One current treatment comes from Regeneron Pharmaceuticals and is a drug called ARCALYST that is an injection released in 2008. This drug blocks the production of IL-1 b so that inflammation is not caused. However, this is dangerous as blocking this protein interferes with the bodies response to infections [4].


 * Current Research ** : Another treatment is a drug called Canakinumab. This is an anti-IL-1 b monoclonal antibody that blocks IL-1 b . This drug is still in clinical trials but it looks promising. After the first trial 34 of the 35 patients had a positive response to the drug. After the second trial all 15 patients receiving the drug remained in remission. However, there were some issues as one patient had to be hospitalized for a lower urinary tract infection and one patient had an episode of vertigo attributed to CAPS. The current mathematical model of this drug predicts that the drug will reduce IL-1 b levels to a normal rate within 8 weeks of treatment [3]. More researchis currently being done on the safety of IL-1 b inhibitors. This research ahs determined that the inhibitors are safe and effective to treat CAPS, but that their full effect oninvolvement needs to be studied more [2].

Works Cited [1] Capscommunity. (2012). Cryopyrin-associated periodic syndromes (CAPS): Overview. http://www.capscommunity.com/caps_fact_caps_pat.html [2] Kone-Paut, I., Piram, M. (2012). Targeting interleukin-1 b in CAPS (cryopyrin-associated periodic) syndromes: What did we learn? Autoimmunity Reviews 12: 7 7-80. [3] Kubota, T., Koike, R. (2010). Cryopyrin-associated periodic syndromes: Background and therapeutics. Mod Rheumatol 20: 213-221 [4] Regeneron. (2013). ARCALYST (rilonacept)- For treatment if Cryopyrin-Associated Periodic Syndromes (CAPS). http://www.regeneron.com/arcalyst