CAPS — sinh bệnh học, biểu hiện và điều trị một bệnh tự miễn

Springer Science and Business Media LLC - Tập 37 - Trang 377-385 - 2015
Jasmin B. Kuemmerle-Deschner1
1Division of Pediatric Rheumatology, Department of Pediatrics, University Children’s Hospital Tuebingen, Tuebingen, Germany

Tóm tắt

Hội chứng chu kỳ liên quan đến cryopyrin (CAPS) là một phổ mức độ nghiêm trọng của các bệnh hiếm gặp. CAPS bao gồm ba tình trạng trước đây được mô tả như hội chứng tự viêm lạnh di truyền (FCAS), hội chứng Muckle-Wells (MWS), và rối loạn viêm đa hệ khởi phát sơ sinh (NOMID), cũng được gọi là hội chứng thần kinh, da và khớp trẻ em mãn tính (CINCA). Biểu hiện lâm sàng của CAPS đặc trưng bởi viêm toàn thân. Các triệu chứng chung là mệt mỏi và sốt. Các biểu hiện tại chỗ ảnh hưởng đến nhiều mô như da, khớp, cơ bắp, mắt và hệ thần kinh trung ương. Những đặc điểm lâm sàng khác biệt là đặc trưng cho mỗi kiểu con của bệnh này. Ở FCAS, các triệu chứng là mề đay do lạnh và sốt, trong MWS thì có bệnh amyloidosis toàn thân và mất thính lực, còn trong NOMID/CINCA có viêm hệ thần kinh trung ương và biến dạng xương. CAPS được gây ra bởi sự đột biến chức năng tăng cường ở dạng đơn lẻ dị hợp tử trong gen NLRP3 mã hóa cho protein cryopyrin. Cryopyrin dẫn dắt sự hình thành một thể tích NLRP3 inflammasome, điều chỉnh sự kích hoạt và cắt khối của caspase-1, cắt các cytokine gây viêm, IL-1β và IL-18. IL-1β đóng vai trò trọng yếu trong việc khởi phát viêm trong CAPS. Điều này đã được xác nhận bởi việc áp dụng các tác nhân chặn IL-1, dẫn đến không những hồi phục nhanh chóng và bền vững các triệu chứng hàng ngày mà còn đến một mức độ nào đó của các di chứng lâu dài của căn bệnh. Để ngăn ngừa tổn thương cơ quan do CAPS gây ra, việc chẩn đoán sớm và khởi động nhanh chóng việc điều trị hiệu quả là điều vô cùng cần thiết.

Từ khóa

#Hội chứng chu kỳ liên quan đến cryopyrin #CAPS #viêm tự miễn #bệnh hiếm gặp #gen NLRP3 #cytokine gây viêm

Tài liệu tham khảo

Hoffman HM, Wanderer AA, Broide DH (2001) Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol 108(4):615–620 Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29(3):301–305 Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, Stein L, Russo R, Goldsmith D, Dent P et al (2002) De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 46(12):3340–3348 Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E, Teillac-Hamel D, Fischer A, de Saint BG (2002) Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet 71(1):198–203 Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H, Aksentijevich I, Lesage S, Waterham H, Wise C, Sarrauste de Menthiere C et al (2008) The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum Mutat 29(6):803–808 Infevers: the registry of hereditary auto-inflammatory disorders mutations. http://fmfighcnrsfr/ISSAID/infevers, last Accessed March 2013 Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R et al (2007) The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 56(4):1273–1285 Kuemmerle-Deschner JB, Lohse P, Koetter I, Dannecker GE, Reess F, Ummenhofer K, Koch S, Tzaribachev N, Bialkowski A, Benseler SM (2011) NLRP3 E311K mutation in a large family with Muckle-Wells syndrome - description of a heterogeneous phenotype and response to treatment. Arthritis Res Ther 13(6):R196 Levy R, Gerard L, Kuemmerle-Deschner J, Lachmann HJ, Kone-Paut I, Cantarini L, Woo P, Naselli A, Bader-Meunier B, Insalaco A et al (2014) Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry. Ann Rheum Dis Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, Nishikomori R, Morimoto T, Kambe N, Goldbach-Mansky R et al (2011) High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum 63(11):3625–3632 Aganna E, Martinon F, Hawkins PN, Ross JB, Swan DC, Booth DR, Lachmann HJ, Bybee A, Gaudet R, Woo P et al (2002) Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum 46(9):2445–2452 Kone-Paut I, Darce-Bello M, Shahram F, Gattorno M, Cimaz R, Ozen S, Cantarini L, Tugal-Tutktun I, Assaad-Khalil S, Hofer M et al (2011) Registries in rheumatological and musculoskeletal conditions. Paediatric Behcet’s disease: an international cohort study of 110 patients. One-year follow-up data. Rheumatology (Oxford) 50(1):184–188 Rieber N, Gavrilov A, Hofer L, Singh A, Oz H, Endres T, Schafer I, Handgretinger R, Hartl D, Kuemmerle-Deschner J (2015) A functional inflammasome activation assay differentiates patients with pathogenic NLRP3 mutations and symptomatic patients with low penetrance variants. Clin Immunol 157(1):56–64 Ye Z, Ting JP (2008) NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr Opin Immunol 20(1):3–9 Petrilli V, Dostert C, Muruve DA, Tschopp J (2007) The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol 19(6):615–622 Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216 Doherty TA, Brydges SD, Hoffman HM (2011) Autoinflammation: translating mechanism to therapy. J Leukoc Biol 90(1):37–47 Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10(2):417–426 Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J (2004) NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20(3):319–325 Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265 Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9(8):847–856 Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9(8):857–865 Jiang Y, Wang M, Huang K, Zhang Z, Shao N, Zhang Y, Wang W, Wang S (2012) Oxidized low-density lipoprotein induces secretion of interleukin-1beta by macrophages via reactive oxygen species-dependent NLRP3 inflammasome activation. Biochem Biophys Res Commun 425(2):121–126 Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nunez G, Schnurr M et al (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464(7293):1357–1361 Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA et al (2009) Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 183(2):787–791 Franchi L, Eigenbrod T, Nunez G (2009) Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol 183(2):792–796 Segovia J, Sabbah A, Mgbemena V, Tsai SY, Chang TH, Berton MT, Morris IR, Allen IC, Ting JP, Bose S (2012) TLR2/MyD88/NF-kappaB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection. PLoS One 7(1):e29695 Ito S, Hara Y, Kubota T (2014) CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction. Arthritis Res Ther 16(1):R52 Goldbach-Mansky R, Kastner DL (2009) Autoinflammation: the prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. J Allergy Clin Immunol 124(6):1141–1149, quiz 1150–1141 Ozkurede VU, Franchi L (2012) Immunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes. Clin Exp Immunol 167(3):382–390 Balavoine JF, de Rochemonteix B, Williamson K, Seckinger P, Cruchaud A, Dayer JM (1986) Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s). J Clin Invest 78(4):1120–1124 Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdal PL, Armes LG, Sommer A, Eisenberg SP, Thompson RC (1990) Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature 343(6256):336–340 Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550 Hawkins PN, Lachmann HJ, McDermott MF (2003) Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med 348(25):2583–2584 Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J, Mueller JL, Anderson JP, Wanderer AA, Firestein GS (2004) Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 364(9447):1779–1785 Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E et al (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 355(6):581–592 Farasat S, Aksentijevich I, Toro JR (2008) Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol 144(3):392–402 Cuisset L, Jeru I, Dumont B, Fabre A, Cochet E, Le Bozec J, Delpech M, Amselem S, Touitou I (2011) Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France. Ann Rheum Dis 70(3):495–499 Stych B, Dobrovolny D (2008) Familial cold auto-inflammatory syndrome (FCAS): characterization of symptomatology and impact on patients’ lives. Curr Med Res Opin 24(6):1577–1582 Toplak I, Rihtaric D, Hostnik P, Grom J, Stukelj M, Valencak Z (2012) Identification of a genetically diverse sequence of porcine reproductive and respiratory syndrome virus in Slovenia and the impact on the sensitivity of four molecular tests. J Virol Methods 179(1):51–56 Fye KH, Siegel DH, Connolly MK (2007) Diagnosis of Muckle-Wells syndrome - 33 years later. J Rheumatol 34(12):2505–2506 Goldbach-Mansky R (2011) Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep 13(2):123–131 Nakagawa K, Gonzalez-Roca E, Souto A, Kawai T, Umebayashi H, Campistol JM, Canellas J, Takei S, Kobayashi N, Callejas-Rubio JL et al (2015) Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes. Ann Rheum Dis 74(3):603–610 Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, Nishikomori R, Morimoto T, Kambe N, Goldbach-Mansky R et al (2011) High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum 63(11):3625–3632 Kastner DL (2005) Hereditary periodic fever syndromes. Hematol Am Soc Hematol Educ Program 2005:74–81 Dollfus H, Hafner R, Hofmann HM, Russo RA, Denda L, Gonzales LD, DeCunto C, Premoli J, Melo-Gomez J, Jorge JP et al (2000) Chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease syndrome: ocular manifestations in a recently recognized chronic inflammatory disease of childhood. Arch Ophthalmol 118(10):1386–1392 Alejandre N, Ruiz-Palacios A, Garcia-Aparicio AM, Blanco-Kelly F, Bermudez S, Fernandez-Sanz G, Romero FI, Arostegui JI, Ayuso C, Jimenez-Alfaro I et al (2014) Description of a new family with cryopyrin-associated periodic syndrome: risk of visual loss in patients bearing the R260W mutation. Rheumatology (Oxford) 53(6):1095–1099 Kawai M, Yoshikawa T, Nishikomori R, Heike T, Takahashi K (2013) Obvious optic disc swelling in a patient with cryopyrin-associated periodic syndrome. Clin Ophthalmol 7:1581–1585 Ahmadi N, Brewer CC, Zalewski C, King KA, Butman JA, Plass N, Henderson C, Goldbach-Mansky R, Kim HJ (2011) Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol–Head Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg 145(2):295–302 Kuemmerle-Deschner JB, Koitschev A, Ummenhofer K, Hansmann S, Plontke SK, Koitschev C, Koetter I, Angermair E, Benseler SM (2013) Hearing loss in Muckle-Wells syndrome. Arthritis Rheum 65(3):824–831 Hill SC, Namde M, Dwyer A, Poznanski A, Canna S, Goldbach-Mansky R (2007) Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA). Pediatr Radiol 37(2):145–152 Dode C, Cuisset L, Delpech M, Grateau G (2003) TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis. J Nephrol 16(3):435–437 Hashkes PJ, Lovell DJ (1997) Recognition of infantile-onset multisystem inflammatory disease as a unique entity. J Pediatr 130(4):513–515 Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, Hawkins PN (2007) Natural history and outcome in systemic AA amyloidosis. N Engl J Med 356(23):2361–2371 Foell D, Wittkowski H, Vogl T, Roth J (2007) S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol 81(1):28–37 Wittkowski H, Kuemmerle-Deschner JB, Austermann J, Holzinger D, Goldbach-Mansky R, Gramlich K, Lohse P, Jung T, Roth J, Benseler SM et al (2011) MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes. Ann Rheum Dis 70(12):2075–2081 Nirmala N, Grom A, Gram H (2014) Biomarkers in systemic juvenile idiopathic arthritis: a comparison with biomarkers in cryopyrin-associated periodic syndromes. Curr Opin Rheumatol 26(5):543–552 Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, Zalewski C, Kim HJ, Bishop R, Hill S et al (2012) Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum 64(7):2375–2386 Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 360(23):2416–2425 Hoffman HM (2009) Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS). Expert Opin Biol Ther 9(4):519–531