Translational Autoinflammatory Disease Section

Raphaela T. Goldbach-Mansky, M.D., M.H.S.
Acting Chief
Phone: 301-435-6243
E-mail: goldbacr@mail.nih.gov

Translational Autoinflammatory Disease Section research focus is on applying a systematic approach to the clinical and immunological description of a number of autoinflammatory diseases. The lab uses targeted interventions to understand the role of specific inflammatory pathways in the pathogenesis of the autoinflammatory diseases. The discovery of single gene mutations, which modify the regulation of inflammatory pathways triggered by exogenous and endogenous “danger” molecules in a number of autoinflammatory diseases has provided new targets to treat and new concepts to understand this disease group. The studies on patients with neonatal-onset multisystem inflammatory disease, NOMID, have demonstrated the pivotal role of IL-1 beta oversecretion on the often devastating inflammatory multiorgan manifestations which include CNS and sensory organ inflammation (i.e. aseptic meningitis, cochlear inflammation and eye inflammation), rash, systemic inflammation with fevers and joint involvement. The overlap of clinical symptoms has led to the investigation of the role of IL-1 in other autoinflammatory/ autoimmune diseases.

Translational Autoinflammatory Disease Section works in partnership with Dr. Dan Kastner the Adjunct Investigator of NIAMS, and his laboratory group. This collaboration has led to the discovery and characterization of genes underlying a number of other autoinflammatory/autoimmune conditions.

Selected Publications

Goldbach-Mansky R. Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin Exp Immunol. 2012 Mar;167(3):391-404. doi: 10.1111/j.1365-2249.2011.04533.x.

Sibley CH, Plass N, Snow J, Wiggs E, Brewer C, King K, Zalewski C, Kim HJ, Bishop R, Hill S, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino F, Stone D, Chapelle D, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease (NOMID) treated with anakinra. Arthritis Rheum. 2012 Jan 31. doi: 10.1002/art.34409. [Epub ahead of print]

Liu Y, Ramot Y, Torrelo A, Paller AS, Si N, Babay S, Kim PW, Sheikh A, Lee CC, Chen Y, Vera A, Zhang X, Goldbach-Mansky R, Zlotogorski A. Mutations in PSMB8 cause CANDLE syndrome with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2011 Sep 27. doi: 10.1002/art.33368

Stojanov S, Lapidus S, Chitkara P, Feder H, Salazar JC, Fleisher TA, Brown MR, Edwards KM, Ward MM, Colbert RA, Sun HW, Wood GM, Barham BK, Jones A, Aksentijevich I, Goldbach-Mansky R, Athreya B, Barron KS, Kastner DL. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. Proc Natl Acad Sci U S A. 2011 Apr 8

Goldbach-Mansky R. Current Status of Understanding the Pathogenesis and Management of Patients With NOMID/CINCA. Curr Rheumatol Rep. 2011 Apr;13(2):123-31.

Ahmadi N, Brewer CC, Zalewski C, King KA, Butman JA, Plass N, Henderson C, Goldbach-Mansky R, Kim HJ. Cryopyrin-Associated Periodic Syndromes: Otolaryngologic and Audiologic Manifestations. Otolaryngol Head Neck Surg. 2011 Mar 31. [Epub ahead of print]

Henderson C, Goldbach-Mansky R. Monogenic autoinflammatory diseases: new insights into clinical aspects and pathogenesis. Curr Opin Rheumatol. 2010 Sep;22(5):567-78.

Fox E, Jayaprakash N, Pham TH, Rowley A, McCully CL, Pucino F, Goldbach-Mansky R. The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates. J Neuroimmunol. 2010 Jun;223(1-2):138-40.

Henderson C, Goldbach-Mansky R. Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: finding the right balance in response to danger signals. Clin Immunol. 2010 May;135(2):210-22.

Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell. 2010 Mar 19;140(6):784-90.

See extended list of publications

Reviewed September 24, 2012