Bertomeu Tomàs, Andrea

Universitat Autònoma de Barcelona. Facultat de Biociències

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 MUCKLE WELLS SYNDROME AS AN EXAMPLE OF HEREDITARY SYSTEMIC AUTOINFLAMMATORY DISEASE Andrea Bertomeu Tomàs Biochemistry  Universitat Autònoma de Barcelona, Barcelona 2014                          1.The Disease: Muckle Wells Syndrome (MWS)   MWS is included in a group of inflammatory diseases called Criopirin Associated Periodic Syndrome (CAPS), at the same time, CAPS are included in a bigger group , Hereditary Systemic Autoinflammatory Diseases (HSAD). All of the syndromes included in CAPS, are associated with mutations in CIAS1 gene , which encodes the protein criopirin.  MWS  is a rare disease (1:1.000.00) that has a high autoinflammatory component. Its inheritance is autosomical dominant. MWS patients show a chronic and systemic inflammation without reason for develop it (no infection, no neoplasic procedure…).   2. Targets • Learn what is the origin of MWS  • What is the molecular  mechanism  of the disease  • What are the current  treatments  •What are the worst symptom  3. Molecular Mechanism             IL-1β    INFLAMMATORY RESPONSE   CIAS1 mutation CRIOPIRIN            CIAS1 mutations cause a bigger gene expression Criopirin levels increase in response at the bigger expression      IL-1 levels increase because criopirin turn on  caspase-1, that cuts the IL-1 and makes it active       IL-1 intermediate the inflammatory response by  macrophages and monocytes and it is    increased  systemically   4. Symptoms Skin Rashes, Pain in the joints, Hearing loss, Fever, Headache, Conjunctivitis, Muscle pain, Proteinuria and   Potential AA Amiloidosis (25%)        5. Treatements                                Inflamation IL-1, IL-6 , TNF Increased SAA  Increased ability to form fibers and aggregates RINOLACEPT CANAKINUMAB IL-1 IL-1R NO SIGNAL RINOLACEPT, FUSION PROTEIN AGAINST IL-1β CANAKINUMAB, HUMAN MONOCLONAL AB AGAINST IL-1 β 6. References 1. Jasmin B.Kuemmerlle-Deschner et al. Efficacy and Safety of Anakinra Therapy in Pediatric and Adult Patients With the Autoinflammatory Muckle-Wells Syndrome. Arthritis & Rheumatism, March 2011; 63, 840-849. 2. Hal M. Hoffman et. Al. Efficacy and Safety of Rinolacept (Interleukin-1 Trap) in Patients with Cryopyrin- Associated Periodic Syndromes. Atritis and Rheumatism 2008, 58; 2443-2452. 3. Juan Ignacio Aróstegui Gorospe. Fisiopatología de las enfermedades autoinflamatorias sistémicas hereditàrias. Hospital clínic Barcelona Servei Immunología. Nº Programa 681. 4. Luis Bolaños,et al. Amiloidosis renal y tiroidea secundaria a síndrome periódico asociado a criopirinas (síndrome de Muckle-Wells) (mutación NLRP3). Nefrología, 2013, Vol33 ; nº 2. NO SIGNAL ANAKINRA,  IL-1R ANTAGONIST  IL-1 ANAKINRA IL-1R INFLANOSOME COMPLEX >127 variants Most missense in exon3 Cross-β amyloid structure. Image from Vanderbilt institute of Chemical Biology References : (1), (2) References: (4) References: (3) 

Muckle Wells syndrome as an example of hereditary systemic autoinflammatory disease

http://ddd.uab.cat/pub/tfg/2014/122726/TFG_andreabertomeutomas.pdf

Muckle Wells syndrome as an example of hereditary systemic autoinflammatory disease

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