Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases
| Title: | Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases |
|---|---|
| Authors: | de Jesus, Adriana A; Hou, Yanfeng; 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, María 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 GP; Punaro, Marilynn G; Reiff, Andreas; Reinhardt, Adam; Rider, Lisa G; Rivas-Chacon, Rafael; Ronis, Tova; Rösen-Wolff, Angela; Roth, Johannes; Ruth, Natasha Mckerran; Rygg, Marite; Schmeling, Heinrike; Schulert, Grant; Scott, Christiaan; Seminario, Gisela; Shulman, Andrew; Sivaraman, Vidya; Son, Mary Beth; Stepanovskyy, 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 |
| Publisher Information: | American Society for Clinical Investigation |
| Publication Year: | 2020 |
| Collection: | The University of Liverpool Repository |
| Description: | 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 ... |
| Document Type: | article in journal/newspaper |
| Language: | English |
| ISSN: | 0021-9738 |
| Relation: | Collapse authors list. de Jesus, Adriana A, Hou, Yanfeng, Brooks, Stephen, Malle, Louise, Biancotto, Angelique, Huang, Yan, Calvo, Katherine R, Marrero, Bernadette, Moir, Susan, Oler, Andrew J et al (show 77 more authors) , 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, María 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 orcid:0000-0002-1295-6179 , 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 GP, Punaro, Marilynn G, Reiff, Andreas, Reinhardt, Adam, Rider, Lisa G, Rivas-Chacon, Rafael, Ronis, Tova, Rösen-Wolff, Angela, Roth, Johannes, Ruth, Natasha Mckerran, Rygg, Marite, Schmeling, Heinrike, Schulert, Grant, Scott, Christiaan, Seminario, Gisela, Shulman, Andrew, Sivaraman, Vidya, Son, Mary Beth, Stepanovskyy, Yuriy, Stringer, Elizabeth, Taber, Sara, Terreri, Maria Teresa, Tifft, Cynthia, Torgerson, Troy, Tosi, Laura, Van Royen-Kerkhof, Annet, Wampler Muskardin, Theresa, Canna, Scott W and Goldbach-Mansky, Raphaela (2020) Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases Journal of Clinical Investigation, 130 (4). pp. 1669-1682. ISSN 0021-9738, 1558-8238 |
| DOI: | 10.1172/jci129301 |
| Availability: | https://livrepository.liverpool.ac.uk/3067981/; https://www.jci.org/articles/view/129301; https://doi.org/10.1172/jci129301 |
| Accession Number: | edsbas.FF20FC73 |
| Database: | BASE |