Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases

• Autores: de Jesus, Adriana A.; Hou, Yangfeng; Brooks, Stephen; Malle, Louise; Biancotto, Angelique; Huang, Yan; Calvo, Katherine R.; Marrero, Bernadette; Moir, Susan; Oler, Andrew J.; Deng, Zuoming; Montealegre Sanchez, Gina A.; Ahmed, Amina; Allenspach, Eric; Arabshahi, Bita; Behrens, Edward; Benseler, Susanne; Bezrodnik, Liliana; Bout Tabaku, Sharon; Brescia, AnneMarie C.; Brown, Diane; Burnham, Jon M.; Caldirola, Maria Soledad; Carrasco, Ruy; Chan, Alice Y.; Cimaz, Rolando; Dancey, Paul; Dare, Jason; DeGuzman, Marietta; Dimitriades, Victoria; Ferguson, Ian; Ferguson, Polly; Finn, Laura; Gattorno, Marco; Grom, Alexei A.; Hanson, Eric P.; Hashkes, Philip J.; Hedrich, Christian M.; Herzog, Ronit; Horneff, Gerd; Jerath, Rita; Kessler, Elizabeth; Kim, Hanna; Kingsbury, Daniel J.; Laxer, Ronald M.; Lee, Pui Y.; Lee Kirsch, Min Ae; Lewandowski, Laura; Li, Suzanne; Lilleby, Vibke; Mammadova, Vafa; Moorthy, Lakshmi N.; Nasrullayeva, Gulnara; O'Neil, Kathleen M.; Onel, Karen; Ozen, Seza; Pan, Nancy; Pillet, Pascal; Piotto, Daniela G.P.; Punaro, Marilynn G.; Reiff, Andreas; Reinhardt, Adam; Rider, Lisa G.; Rivas Chacon, Rafael; Ronis, Tova; Rösen Wolff, Angela; Roth, Johannes; Mckerran Ruth, Natasha; Rygg, Marite; Schmeling, Heinrike; Schulert, Grant; Scott, Christiaan; Seminario, Gisella; Shulman, Andrew; Sivaraman, Vidya; Son, Mary Beth; Stepanovskiy, Yuriy; Stringer, Elizabeth; Taber, Sara; Terreri, Maria Teresa; Tifft, Cynthia; Torgerson, Troy; Tosi, Laura; van Royen Kerkhof, Annet; Wampler Muskardin, Theresa; Canna, Scott W.; Goldbach Mansky, Raphaela
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Autoinflammatory interferonopathies; Macrophage activation syndrome
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.
Fil: de Jesus, Adriana A.. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Hou, Yangfeng. Shandong University; China
Fil: Brooks, Stephen. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos
Fil: Malle, Louise. cahn School of Medicine at Mount Sinai; Estados Unidos
Fil: Biancotto, Angelique. No especifíca;
Fil: Huang, Yan. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Calvo, Katherine R.. National Institutes of Health; Estados Unidos
Fil: Marrero, Bernadette. No especifíca;
Fil: Moir, Susan. No especifíca;
Fil: Oler, Andrew J.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos
Fil: Deng, Zuoming. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos
Fil: Montealegre Sanchez, Gina A.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos
Fil: Ahmed, Amina. No especifíca;
Fil: Allenspach, Eric. Washington State University; Estados Unidos
Fil: Arabshahi, Bita. Virginia Commonwealth University; Estados Unidos
Fil: Behrens, Edward. University of Pennsylvania; Estados Unidos
Fil: Benseler, Susanne. University of Calgary; Canadá
Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bout Tabaku, Sharon. No especifíca;
Fil: Brescia, AnneMarie C.. No especifíca;
Fil: Brown, Diane. No especifíca;
Fil: Burnham, Jon M.. University of Pennsylvania; Estados Unidos
Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Carrasco, Ruy. No especifíca;
Fil: Chan, Alice Y.. University of California; Estados Unidos
Fil: Cimaz, Rolando. Università degli Studi di Milano; Italia
Fil: Dancey, Paul. Janeway Children's Hospital And Rehabilitation Centre; Canadá
Fil: Dare, Jason. University of Arkansas for Medical Sciences; Estados Unidos
Fil: DeGuzman, Marietta. Baylor College Of Medicine; Estados Unidos
Fil: Dimitriades, Victoria. No especifíca;
Fil: Ferguson, Ian. University of Yale. School of Medicine; Estados Unidos
Fil: Ferguson, Polly. University of Iowa; Estados Unidos
Fil: Finn, Laura. University of Washington; Estados Unidos
Fil: Gattorno, Marco. No especifíca;
Fil: Grom, Alexei A.. No especifíca;
Fil: Hanson, Eric P.. No especifíca;
Fil: Hashkes, Philip J.. No especifíca;
Fil: Hedrich, Christian M.. University of Liverpool; Reino Unido
Fil: Herzog, Ronit. University of New York; Estados Unidos
Fil: Horneff, Gerd. Universitat zu Köln; Alemania
Fil: Jerath, Rita. Augusta University; Estados Unidos
Fil: Kessler, Elizabeth. University of Missouri; Estados Unidos
Fil: Kim, Hanna. No especifíca;
Fil: Kingsbury, Daniel J.. No especifíca;
Fil: Laxer, Ronald M.. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Lee, Pui Y.. Children's Hospital Boston; Estados Unidos
Fil: Lee Kirsch, Min Ae. Technische Universität Dresden; Alemania
Fil: Lewandowski, Laura. No especifíca;
Fil: Li, Suzanne. Hackensack University Medical Center; Estados Unidos
Fil: Lilleby, Vibke. Oslo University Hospital; Noruega
Fil: Mammadova, Vafa. Azerbaijan Medical University; Azerbaiyán
Fil: Moorthy, Lakshmi N.. Robert Wood Johnson Medical School; Estados Unidos
Fil: Nasrullayeva, Gulnara. Azerbaijan Medical University; Azerbaiyán
Fil: O'Neil, Kathleen M.. Riley Hospital for Children; Estados Unidos
Fil: Onel, Karen. Hospital for Special Surgery; Estados Unidos
Fil: Ozen, Seza. Hacettepe University; Turquía
Fil: Pan, Nancy. Hospital for Special Surgery; Estados Unidos
Fil: Pillet, Pascal. Children Hospital Pellegrin-Enfants; Francia
Fil: Piotto, Daniela G.P.. Universidade Federal de Sao Paulo; Brasil
Fil: Punaro, Marilynn G.. University of Texas; Estados Unidos
Fil: Reiff, Andreas. University of Nebraska; Estados Unidos
Fil: Reinhardt, Adam. University of Nebraska; Estados Unidos
Fil: Rider, Lisa G.. No especifíca;
Fil: Rivas Chacon, Rafael. Nicklaus Children’s Hospital; Estados Unidos
Fil: Ronis, Tova. Children’s National Health System; Estados Unidos
Fil: Rösen Wolff, Angela. Technische Universität Dresden; Alemania
Fil: Roth, Johannes. Children’s Hospital of Eastern Ontario; Canadá
Fil: Mckerran Ruth, Natasha. Medical University of South Carolina; Estados Unidos
Fil: Rygg, Marite. Norwegian University of Science and Technology; Noruega
Fil: Schmeling, Heinrike. University of Calgary; Canadá
Fil: Schulert, Grant. Children’s Hospital Medical Center; Estados Unidos
Fil: Scott, Christiaan. University of Cape Town; Sudáfrica
Fil: Seminario, Gisella. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Shulman, Andrew. University of California at Irvine; Estados Unidos
Fil: Sivaraman, Vidya. Nationwide Children’s Hospital; Estados Unidos
Fil: Son, Mary Beth. Boston Children’s Hospital; Estados Unidos
Fil: Stepanovskiy, Yuriy. Shupyk National Medical Academy for Postgraduate Education; Ucrania
Fil: Stringer, Elizabeth. Dalhousie University Halifax; Canadá
Fil: Taber, Sara. Hospital for Special Surgery; Estados Unidos
Fil: Terreri, Maria Teresa. Universidade Federal de Sao Paulo; Brasil
Fil: Tifft, Cynthia. No especifíca;
Fil: Torgerson, Troy. University of Washington; Estados Unidos
Fil: Tosi, Laura. Children’s National Health System; Estados Unidos
Fil: van Royen Kerkhof, Annet. Wilhelmina Children’s Hospital Utrech; Países Bajos
Fil: Wampler Muskardin, Theresa. New York University School of Medicine; Estados Unidos
Fil: Canna, Scott W.. University of Pittsburgh; Estados Unidos
Fil: Goldbach Mansky, Raphaela. National Institute Of Allergy And Infectious Diseases ; Estados Unidos