Experience of the successful treatment with canakinumab of a patient with NLPC4-associated autoinflammatory syndrome with enterocolitis

The article shows the observation of rare NLPC4-associated autoinflammatory syndrome with enterocolitis and familial cold urticaria. Diagnosis is confirmed molecularly-genetically: previously not described mutation c.928C>T in the heterozygous state in NLRC4 gene is discovered by a method of the new generation sequencing. The use of a monoclonal antibody to the interleukin 1 canakinumab provided complete relief of fever and skin and intestinal symptoms in just 1 week of treatment. Later the signs of inflammation have disappeared completely; the patient’s quality of life improved and life-threatening complications were prevented. The above example demonstrates the high clinical efficacy of canakinumab in the patient with NLRC4-associated autoinflammatory syndrome and suggests promising therapeutic use of interleukin 1 blockers in such patients. There were no adverse events during canakinumab therapy.

1. www.printo.it [Internet]. Eurofever Project [cited 2016 Apr 14]. Available from: https://www.printo.it/eurofever.

2. Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-1betaprocessing inflammasome with increased activity in Muckle–Wells auto-inflammatory disorder. Immunity. 2004;20(3):319–325. doi: 10.1016/s1074-7613(04)00046-9.

3. Hoffman HM, Mueller JL, Broide DH, et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome. Nat Genet. 2001;29(3):301–305. doi: 10.1038/ng756.

4. Romberg N, Al Moussawi K, Nelson-Williams C, et al. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflam mation. Nat Genet. 2014;46(10):1135–1139. doi:10.1038/ng.3066.

5. Canna SW, de Jesus AA, Gouni S, et al. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014;46(10): 1140–1146. doi:10.1038/ng.3089.

6. Ozturk A, Ozcakar B, Ekim M. Akar N. Is MEFV gene Arg202Gln (605 G>A) a disease-causing mutation? Turk J Med Sci. 2008; 38(3):205–208.

7. Kallinich T, Haffner D, Niehues T, et al. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics. 2007;119(2):e474–e483. doi: 10.1542/peds.2006-1434.

8. Pavlopoulos GA, Oulas A, Iacucci E, et al. Unraveling genomic variation from next generation sequencing data. BioData Min. 2013;6(1):13. doi: 10.1186/1756-0381-6-13.

9. Hu Z, Yan C, Liu P, et al. Crystal structure of NLRC4 reveals its autoinhibition mechanism. Science. 2013;341(6142):172–175. doi: 10.1126/science.1236381.

10. Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355(6):581–592. doi: 10.1056/nejmoa055137.

11. Kitamura A, Sasaki Y, Abe T, et al. An inherited mutation in NLRC4 causes autoinflammation in human and mice. J Exp Med. 2014;211(12):2385–2396. doi: 10.1084/jem.20141091.

12. Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, et al. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. doi: 10.1186/ar3535.

13. Kuemmerle-Deschner JB, Ramos E, Blank N, et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remis sion in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13(1):R34. doi: 10.1186/ar3266.

14. Kuemmerle-Deschner JB, Hachulla E, Cartwright R, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70(12):2095–2102. doi: 10.1136/ard.2011.152728.

15. Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle–Wells syndrome. Arthritis Rheum. 2011;63(3):840–849. doi: 10.1002/art.30149.

16. Thornton BD, Hoffman HM, Bhat A, Don BR. Successful treatment of renal amyloidosis due to familial cold autoinflammatory syndrome using an interleukin 1 receptor antagonist. Am J Kidney Dis. 2007;49(3):477–481. doi: 10.1053/j.ajkd.2006.10.026.