Translational Autoinflammatory Diseases Section
Adriana A. de Jesus, M.D., Ph.D.
Staff Clinician
Assistant Research Physician
Specialty(s): Pediatrics, Rheumatology Provides direct clinical care to patients at NIH Clinical Center
Major Areas of Research
- Identify genetic causes of undifferentiated systemic autoinflammatory diseases by next-generation sequencing
- Identify genetic diagnoses in patients affected by early onset Type I interferon (IFN)-mediated autoinflammatory diseases (interferonopathies)
- Study the pathogenesis of Type I interferonopathies, including proteasome-associated autoinflammatory syndromes (PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), and undifferentiated Type I interferonopathies
- Diagnose and treat patients with systemic autoinflammatory diseases
Program Description
Dr. Adriana de Jesus is an assistant research physician in pediatric rheumatology translational research, particularly studying the genetic basis and pathogenic mechanisms of systemic autoinflammatory diseases (SAIDs).
She began investigating the genetic causes of autoinflammatory diseases while working on her Ph.D. in Brazil. She collaborated with the Translational Autoinflammatory Diseases Section (TADS) at NIH to report the first two Brazilian patients with a deficiency of interleukin 1 receptor antagonist (DIRA).
She also led a multicenter study for the genetic investigation of 102 patients with clinically suspected autoinflammatory diseases in Brazil. Since joining TADS in 2012, under the leadership of Dr. Raphaela Goldbach-Mansky, she has been responsible for the genetic investigation of patients with undifferentiated SAIDs enrolled into an NIH natural history protocol who undergo trio exome or genome sequencing.
Dr. Adriana de Jesus’ role in TADS involves generating and interpreting genetic data and playing a key part in the phenotypic characterizations of the patient cohorts. At TADS, she identified de novo variants in STING1 as the cause of STING-associated vasculopathy with onset in infancy (SAVI), allowing these patients to be treated with interferon-blocking therapies. She also identified de novo variants in NLRC4 and CDC42 as the genetic defect in two novel autoinflammatory diseases associated with macrophage activation syndrome (MAS).
Other significant contributions included the identification of variants in PSMG2 and PSMA5 in patients with proteasome-associated autoinflammatory syndromes (PRAAS), and IKBKG splice-site variants and SAMD9L frame-shift variants in patients with NEMO-deleted exon 5 autoinflammatory syndrome (NEMO-NDAS) and SAMD9L-associated autoinflammatory disease (SAAD), respectively.
She has also described a novel SAID caused by gain-of-function variants in LYN and characterized by skin vasculitis and liver fibrosis. Her contributions to the research on SAIDs also extend to the development and validation of a Type I interferon score assay, which is used as a biomarker to aid in the diagnosis and assessment of treatment responses in patients with Type I interferonopathies.
Biography
Education
Ph.D., 2011, University of Sao Paulo, Sao Paulo, SP, Brazil
M.D., 2002, Federal University of Bahia, Salvador, BA, Brazil
In 2007, Dr. de Jesus completed her residency and fellowship in pediatric rheumatology at the University of Sao Paulo, Sao Paulo, SP, Brazil, and her pediatrics residency in 2005 at the University of Sao Paulo, Sao Paulo, SP, Brazil.
Languages Spoken
PortugueseDr. de Jesus was born and raised in Brazil. She obtained an M.D. from the Federal University of Bahia, Brazil, in 2002. She completed a pediatrics residency followed by a pediatric rheumatology residency and fellowship at the University of Sao Paulo, Brazil.
In 2011, Dr. de Jesus received her Ph.D. from the University of Sao Paulo, Brazil. In 2012, she joined the Translational Autoinflammatory Diseases Section (TADS), headed by Dr. Raphaela Goldbach-Mansky, as a postdoctoral fellow. In 2016, she was appointed as a staff scientist, and she is currently a staff clinician within TADS.
Clinical Studies
Selected Publications
de Jesus AA, Chen G, Yang D, Brdicka T, Ruth NM, Bennin D, Cebecauerova D, Malcova H, Freeman H, Martin N, Svojgr K, Passo MH, Bhuyan F, Alehashemi S, Rastegar AT, Uss K, Kardava L, Marrero B, Duric I, Omoyinmi E, Peldova P, Lee CR, Kleiner DE, Hadigan CM, Hewitt SM, Pittaluga S, Carmona-Rivera C, Calvo KR, Shah N, Balascakova M, Fink DL, Kotalova R, Parackova Z, Peterkova L, Kuzilkova D, Campr V, Sramkova L, Biancotto A, Brooks SR, Manes C, Meffre E, Harper RL, Kuehn H, Kaplan MJ, Brogan P, Rosenzweig SD, Merchant M, Deng Z, Huttenlocher A, Moir SL, Kuhns DB, Boehm M, Skvarova Kramarzova K, Goldbach-Mansky R. Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome. Nat Commun. 2023 Mar 17;14(1):1502.
de Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y, Calvo KR, Marrero B, Moir S, Oler AJ, Deng Z, Montealegre Sanchez GA, Ahmed A, Allenspach E, Arabshahi B, Behrens E, Benseler S, Bezrodnik L, Bout-Tabaku S, Brescia AC, Brown D, Burnham JM, Caldirola MS, Carrasco R, Chan AY, Cimaz R, Dancey P, Dare J, DeGuzman M, Dimitriades V, Ferguson I, Ferguson P, Finn L, Gattorno M, Grom AA, Hanson EP, Hashkes PJ, Hedrich CM, Herzog R, Horneff G, Jerath R, Kessler E, Kim H, Kingsbury DJ, Laxer RM, Lee PY, Lee-Kirsch MA, Lewandowski L, Li S, Lilleby V, Mammadova V, Moorthy LN, Nasrullayeva G, O'Neil KM, Onel K, Ozen S, Pan N, Pillet P, Piotto DG, Punaro MG, Reiff A, Reinhardt A, Rider LG, Rivas-Chacon R, Ronis T, Rösen-Wolff A, Roth J, Ruth NM, Rygg M, Schmeling H, Schulert G, Scott C, Seminario G, Shulman A, Sivaraman V, Son MB, Stepanovskiy Y, Stringer E, Taber S, Terreri MT, Tifft C, Torgerson T, Tosi L, Van Royen-Kerkhof A, Wampler Muskardin T, Canna SW, Goldbach-Mansky R. Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases. J Clin Invest. 2020 Apr 1;130(4):1669-1682.
de Jesus AA, Brehm A, VanTries R, Pillet P, Parentelli AS, Montealegre Sanchez GA, Deng Z, Paut IK, Goldbach-Mansky R, Krüger E. Novel proteasome assembly chaperone mutations in PSMG2/PAC2 cause the autoinflammatory interferonopathy CANDLE/PRAAS4. J Allergy Clin Immunol. 2019;143(5):1939-1943.
Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y, DiMattia MA, Zaal KJ, Sanchez GA, Kim H, Chapelle D, Plass N, Huang Y, Villarino AV, Biancotto A, Fleisher TA, Duncan JA, O'Shea JJ, Benseler S, Grom A, Deng Z, Laxer RM, Goldbach-Mansky R. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014 Oct;46(10):1140-6.
Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS, Lee CR, DiMattia MA, Cowen EW, Gonzalez B, Palmer I, DiGiovanna JJ, Biancotto A, Kim H, Tsai WL, Trier AM, Huang Y, Stone DL, Hill S, Kim HJ, St Hilaire C, Gurprasad S, Plass N, Chapelle D, Horkayne-Szakaly I, Foell D, Barysenka A, Candotti F, Holland SM, Hughes JD, Mehmet H, Issekutz AC, Raffeld M, McElwee J, Fontana JR, Minniti CP, Moir S, Kastner DL, Gadina M, Steven AC, Wingfield PT, Brooks SR, Rosenzweig SD, Fleisher TA, Deng Z, Boehm M, Paller AS, Goldbach-Mansky R. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014 Aug 7;371(6):507-518.
Jesus AA, Osman M, Silva CA, Kim PW, Pham TH, Gadina M, Yang B, Bertola DR, Carneiro-Sampaio M, Ferguson PJ, Renshaw BR, Schooley K, Brown M, Al-Dosari A, Al-Alami J, Sims JE, Goldbach-Mansky R, El-Shanti H. A novel mutation of IL1RN in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis Rheum. 2011 Dec;63(12):4007-17.