Psoriasis pustulosa generalizada: de la inmunopatogénesis a la clínica
DOI:
https://doi.org/10.29176/2590843X.9Palabras clave:
deficiencia del antagonista del receptor de la interleucina 36, interleucina 36, receptor de interleucina 36, proteína IL-36Ra, proteína L-36ª, proteína IL-36B, psoriasis pustulosa, IL36RN, enfermedades autoinflamatorias hereditariasResumen
El síndrome DITRA (Interleukin-36-Receptor Antagonist Deficiency) es una enfermedad autoinflamatoria debida a mutaciones del gen IL36RN que producen deficiencia del antagonista del receptor de la IL-36, lo que induce una cascada inflamatoria que lleva a un cuadro clínico grave de psoriasis pustulosa generalizada. Ante desencadenantes externos, como los componentes de agentes infecciosos que son activadores de los receptores de inmunidad innata, denominados PAMP (Pathogen-Associated Molecular Patterns), o los asociados a estrés celular, llamados DAMP (Damage-Associated Molecular Patterns), se activa el receptor con gran homología a los TLR (Toll-Like Receptors) y se amplifica a través del receptor de la IL-36, que en ausencia de su antagonista, conlleva a mayor activación celular en el principal órgano blanco, que es la piel.
El síndrome DITRA debe sospecharse en todo paciente con psoriasis pustulosa generalizada grave, para enfocar apropiadamente su tratamiento.
Biografía del autor/a
Andrea Castaño, Universidad de Antioquia
Médica, residente de Dermatología, Universidad de Antioquia, Medellín, Colombia
Margarita María Velásquez, Universidad de Antioquia
Médica dermatóloga, Ph.D. en Ciencias Básicas Biomédicas; docente de Dermatología, Universidad de Antioquia; Centro de Investigaciones Dermatológicas CIDERM, Medellín, Colombia.
Referencias bibliográficas
Rubartelli A. Autoinflammatory diseases. Im-munol Lett. 2014;161:226-30.
Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: The molecular patho-physiology of autoinflammatory disease. Annu Rev Immunol. 2009;27:621-68.
Moll M, Kuemmerle-Deschner JB. Inflammasome and cytokine blocking strategies in autoinflamma-tory disorders. Clin Immunol. 2013;147:242-75.
Günther S, Sundberg EJ. Molecular determinants of agonist and antagonist signaling through the IL-36 receptor. J Immunol. 2014;193:921-30.
Moghaddas F, Masters SL. Monogenic autoin-flammatory diseases: Cytokinopathies. Cytokine. 2015;74:237-46.
Clavel G, Thiolat A, Boissier MC. Interleukin newcomers creating new numbers in rheumato-logy: IL-34 to IL-38. Joint Bone Spine. 2013;80:449- 53.
Sánchez GA, de Jesús AA, Goldbach-Mansky R. Monogenic autoinflammatory diseases: Disorders of amplified danger sensing and cytokine dysregu-lation. Rheum Dis Clin North Am. 2013;39:701-34.
Gurung P, Kanneganti TD. Autoinflammatory skin disorders: The inflammasomme in focus. Trends Mol Med. 2016;22:545-64.
Picard C, Al-Herz W, Bousfiha A, Casanova JL, Cha-tila T, Conley ME, et al. Primary immunodeficiency diseases: An update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696-726.
Abbas O, Itani S, Ghosn S, Kibbi AG, Fidawi G, Farooq M, et al. Acrodermatitis continua of Hallo-peau is a clinical phenotype of DITRA: Evidence that it is a variant of pustular psoriasis. Dermato-logy. 2013;226:28-31.
Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, et al. Interleukin-36-receptor anta-gonist deficiency and generalized pustular pso-riasis. N Engl J Med. 2011;365:620-8.
Dinarello CA. Overview of the interleukin-1 fa-mily of ligands and receptors. Semin Immunol. 2013;25:389-93.
Boraschi D, Tagliabue A. The interleukin-1 re-ceptor family. Semin Immunol. 2013;25:394-407.
Lamacchia C, Palmer G, Rodríguez E, Martin P, Vigne S, Seemayer CA, et al. The severity of expe-rimental arthritis is independent of IL-36 receptor signaling. Arthritis Res Ther. 2013;15:R38.
Gresnigt MS, van de Veerdonk FL. Biology of IL-36 cytokines and their role in disease. Semin Im-munol. 2013;25:458-65.
Blumberg H, Dinh H, Trueblood ES, Pretorius J, Kugler D, Weng N, et al. Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med. 2007;204:2603-14.
Derer A, Groetsch B, Harre U, Böhm C, Towne J, Schett G, et al. Blockade of IL-36 receptor signa-ling does not prevent from TNF-induced arthritis. PLoS One. 2014;9:e101954.
Debets R, Timans JC, Homey B, Zurawski S, Sana TR, Lo S, et al. Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2. J Immunol. 2001;167:1440-6.
Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M, Gabel CA, et al. Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36α, IL-36β, and IL-36γ) or antagonist (IL-36Ra) acti-vity. J Biol Chem. 2011;286:42594-602.
Farooq M, Nakai H, Fujimoto A, Fujikawa H, Mat-suyama A, Kariya N, et al. Mutation analysis of the IL36RN gene in 14 Japanese patients with genera-lized pustular psoriasis. Hum Mutat. 2013;34:176-83.
Foster AM, Baliwag J, Chen CS, Guzmán AM, Stoll SW, Gudjonsson JE, et al. IL-36 promotes myeloid cell infiltration, activation, and inflammatory acti-vity in skin. J Immunol. 2014;192:6053-61.
van de Veerdonk FL, Stoeckman AK, Wu G, Boec-kermann AN, Azam T, Netea MG, et al. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. Proc Natl Acad Sci U S A. 2012;109:3001-5.
van de Veerdonk FL, Netea MG. New Insights in the immunobiology of IL-1 family members. Front Immunol. 2013;4:167.
Palomo J, Dietrich D, Martin P, Palmer G, Gabay C. The interleukin (IL)-1 cytokine family - Balance between agonists and antagonists in inflamma-tory diseases. Cytokine. 2015;76:25-37.
Dunn EF, Gay NJ, Bristow AF, Gearing DP, O'Neill LA, Pei XY. High-resolution structure of murine in-terleukin 1 homologue IL-1F5 reveals unique loop conformations for receptor binding specificity. Biochemistry. 2003;42:10938-44.
Abbas AK, Lichtman AH, Pillai S. Inmunología ce-lular y molecular. Octava edición. Barcelona: Else-vier España; 2015. p. 545
Naik HB, Cowen EW. Autoinflammatory pustular neutrophilic diseases. Dermatol Clin. 2013;31:405-25.
Martin MU, Wesche H. Summary and comparison of the signaling mechanisms of the Toll/inter-leukin-1 receptor family. Biochim Biophys Acta. 2002;1592:265-80.
Sugiura K. The genetic background of genera-lized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants. J Dermatol Sci. 2014;74:187-92.
Towne JE, Garka KE, Renshaw BR, Virca GD, Sims JE. Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem. 2004;279:13677-88.
Vigne S, Palmer G, Lamacchia C, Martin P, Ta-labot-Ayer D, Rodríguez E, et al. IL-36R ligands are potent regulators of dendritic and T cells. Blood. 2011;118:5813-23.
Keermann M, Kõks S, Reimann E, Abram K, Erm T, Silm H, et al. Expression of IL-36 family cytokines and IL-37 but not IL-38 is altered in psoriatic skin. J Dermatol Sci. 2015;80:150-2.
Tortola L, Rosenwald E, Abel B, Blumberg H, Schäfer M, Coyle AJ, et al. Psoriasiform derma-titis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin Invest. 2012;122:3965-76.
Carrier Y, Ma HL, Ramon HE, Napierata L, Small C, O'Toole M, et al. Inter-regulation of Th17 cyto-kines and the IL-36 cytokines in vitro and in vivo: Implications in psoriasis pathogenesis. J Invest Dermatol. 2011;131:2428-37.
Gabay C, Towne JE. Regulation and function of in-terleukin-36 cytokines in homeostasis and patho-logical conditions 2015; 97.
Kanazawa N, Nakamura T, Mikita N, Furukawa F. Novel IL36RN mutation in a Japanese case of early onset generalized pustular psoriasis. J Dermatol. 2013;40:749-51.
Tominaga C, Yamamoto M, Imai Y, Yamanishi K. A case of old age-onset generalized pustular pso-riasis with a deficiency of IL-36RN (DITRA) treated by granulocyte and monocyte apheresis. Case Rep Dermatol. 2015;7:29-35.
Sugiura K, Takemoto A, Yamaguchi M, Taka-hashi H, Shoda Y, Mitsuma T, et al. The majority of generalized pustular psoriasis without pso-riasis vulgaris is caused by deficiency of inter-leukin-36 receptor antagonist. J Invest Dermatol. 2013;133:2514-21.
Li M, Han J, Lu Z, Li H, Zhu K, Cheng R, et al. Prevalent and rare mutations in IL-36RN gene in Chinese patients with generalized pustular pso-riasis and psoriasis vulgaris. J Invest Dermatol. 2013;133:2637-9.
Li X, Chen M, Fu X, Zhang Q, Wang Z, Yu G, et al. Mutation analysis of the IL36RN gene in Chi-nese patients with generalized pustular psoriasis with/without psoriasis vulgaris. J Dermatol Sci. 2014;76:132-8.
Capon F. IL36RN mutations in generalized pus-tular psoriasis: Just the tip of the iceberg? J Invest Dermatol. 2013;133:2503-4.
Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, Arostegui JI, et al. IL36RN mutations define a severe autoinflammatory phenotype of genera-lized pustular psoriasis. J Allergy Clin Immunol. 2015;135:1067-70.e9.
Cowen EW, Goldbach-Mansky R. DIRA, DITRA, and new insights into pathways of skin inflammation: What's in a name? Arch Dermatol. 2012;148:381-4.
Johnston A, Xing X, Guzmán AM, Riblett M, Loyd CM, Ward NL, et al. IL-1F5, -F6, -F8, and -F9: A novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J Immunol. 2011;186:2613-22.
Ramadas RA, Ewart SL, Iwakura Y, Medoff BD, Le-Vine AM. IL-36α exerts pro-inflammatory effects in the lungs of mice. PLoS One. 2012;7:e45784.
Almeida de Jesús A, Goldbach-Mansky R. Mono-genic autoinflammatory diseases: concept and cli-nical manifestations. Clin Immunol. 2013;147:155-74.
Setta-Kaffetzi N, Navarini AA, Patel VM, Pulla-bhatla V, Pink AE, Choon SE, et al. Rare patho-genic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. J Invest Dermatol. 2013;133:1366-9.
Sugiura K, Endo K, Akasaka T, Akiyama M. Suc-cessful treatment with infliximab of sibling cases with generalized pustular psoriasis caused by de-ficiency of interleukin-36 receptor antagonist. J Eur Acad Dermatol Venereol. 2015;29:2054-6.
Pan J, Qiu L, Xiao T, Chen HD. Juvenile genera-lized pustular psoriasis with IL36RN mutation treated with short-term infliximab. Dermatol Ther. 2016;29:164-7.
Arakawa A, Ruzicka T, Prinz JC. Therapeutic efficacy of interleukin 12/interleukin 23 bloc-kade in generalized pustular psoriasis regard-less of IL36RN mutation satus. JAMA Dermatol. 2016;152:825-8.
Hüffmeier U, Wätzold M, Mohr J, Schön MP, Mössner R. Successful therapy with anakinra in a patient with generalized pustular pso-riasis carrying IL36RN mutations. Br J Dermatol. 2014;170:202-4.
Rossi-Semerano L, Piram M, Chiaverini C, De Ri-caud D, Smahi A, Koné-Paut I. First clinical des-cription of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra. Pediatrics. 2013;132:e1043-7.
Podlipnik S, de la Mora L, Alsina M, Mascaró JM Jr. Pneumocystis jirovecii pneumonia in a patient with pustular psoriasis with an IL-36RN deficiency treated with infliximab: Case report and review of the literature. Australas J Dermatol. 2017;58:e44-7.
Wolf J, Ferris LK. Anti-IL-36R antibodies, poten-tially useful for the treatment of psoriasis: A pa-tent evaluation of WO2013074569. 2014;24:477-9.
Cómo citar
Descargas
Descargas
Publicado
Cómo citar
Número
Sección
| Estadísticas de artículo | |
|---|---|
| Vistas de resúmenes | |
| Vistas de PDF | |
| Descargas de PDF | |
| Vistas de HTML | |
| Otras vistas | |
