Bryce A. Binstadt, M.D., Ph.D.

Research Interests:

Autoimmunity, Innate Immunity

Our laboratory investigates the mechanisms by which systemic autoimmune diseases lead to tissue damage. We utilize the K/BxN T cell receptor transgenic mouse model of inflammatory arthritis. In this model, mice spontaneously develop arthritis-inducing antibodies that recognize a ubiquitously-expressed self-antigen. Passive transfer of these autoantibodies causes arthritis in normal mice, and this inflammatory response depends on cells and molecules of the innate immune system. The mechanisms by which autoantibodies directed against a widely-expressed protein lead to joint-restricted disease remain incompletely defined. Ongoing projects in the laboratory are aimed at determining a) how the systemic autoimmune response in K/BxN mice damages organs other than synovial joints, b) how the vascular endothelium contributes to the pathogenesis of inflammation and target-tissue specificity in this model, and c) how novel pro-inflammatory molecules promote the development of arthritis. We hope that these investigations will lead to the development of new therapeutic strategies for treating systemic autoimmune diseases.

Clinical website - Division of Pediatric Rheumatology

Basic Science Publications:

• Auger, J.L., Haasken, S.S., Binstadt, B.A. 2012. Autoantibody-mediated arthritis in the absence of C3 and activating Fcgamma receptors: C5 is activated by the coagulation cascade. Arthritis Res. Ther. 14(6):R269.
• Auger, J. L., Haasken, S., Steinert, E. M. and Binstadt, B. A. 2012. Incomplete TCR-β allelic exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice. Eur. J. Immunol.. doi: 10.1002/eji.201242520
• Rao SM, Auger JL, Gaillard P, Weissleder R, Wada E, Torres R, Kojima M, Benoist C, Mathis D, Binstadt BA. 2012. The neuropeptide neuromedin U promotes autoantibody-mediated arthritis. Arthritis Res Ther.14(1):R29. [Epub ahead of print]
• Haasken SS, Hebert JL, Binstadt BA. Absence of b2 integrins impairs regulatory T Cells and exacerbates CD4+ T cell-dependent autoimmune carditis. J. Immunol. Prepublished online 27 July 2011, doi:10.4049/jimmunol.1000967
• Binstadt, BA, Hebert JL, Ortiz-Lopez A, Bronson R, Benoist C, Mathis D. 2009. The same systemic autoimmune disease provokes arthritis and endocarditis via distinct mechanisms. Proc Natl Acad Sci USA 106:16758-63.
  
• Wu HJ, Sawaya H, Binstadt B, Brickelmaier M, Blasius A, Gorelik L, Mahmood U, Weissleder R, Carulli J, Benoist C, Mathis D. 2007. Inflammatory arthritis can be reined in by CpG-induced DC NK cell cross talk. J Exp Med 204: 1911-22.
  
• Nigrovic PA, Binstadt BA, Monach PA, Johnsen A, Gurish M, Iwakura Y, Benoist C, Mathis D, Lee DM. 2007. Mast cells contribute to the initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci USA 104: 2325-30.
  
• Binstadt BA, Patel PR, Alencar H, Nigrovic PA, Lee DM, Mahmood U, Weissleder R, Mathis D, Benoist C. 2006. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7: 284-92.
  
• Binstadt BA, Billadeau DD, Jevremovic D, Williams BL, Yi T, Koretzky GA, Abraham RT, Leibson PJ. 1998. SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors. J Biol Chem 273: 27518-23.
  
• Brumbaugh KM, Binstadt BA, Billadeau DD, Schoon RA, Dick CJ, Ten RM, Leibson PJ. 1997. Functional role for Syk tyrosine kinase in NK cell-mediated natural cytotoxicity. J Exp Med 186: 1965-74.
  
• Binstadt BA, Brumbaugh KM, Dick CJ, Scharenberg AM, Williams BL, Colonna M, Lanier LL, Kinet J-P, Abraham RT, Leibson PJ. 1996. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Immunity 5: 629-38.
  
• Einspahr KJ, Abraham RT, Binstadt BA, Uehara Y, Leibson PJ. 1991. Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function. Proc Natl Acad Sci USA 88: 6279-83.
  

 

Clinical Publications:

• Taxter AJ, Bellin MD, Binstadt BA. Pericarditis as the presenting feature of adrenoleukodystrophy. Pediatrics, 2011; 127: e771-4.
• Stingl C, Moller JH, Binstadt BA. 2009. Cardiac Operations for North American Children with Rheumatic Diseases: 1985-2005. Pediatr Cardiol. (Epub ahead of print).
  
• Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, Binstadt BA, Filipovich A, Grom AA. 2008. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 58(9):2892-6.
  
• Hazen MM, Woodward AL, Hofmann I, Degar BA, Grom A, Filipovich AH, Binstadt BA. 2008. Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. Arthritis Rheum.58(2):567-570 [Epub ahead of print]
  
• El-Hallak M*, Binstadt BA*, Leichtner AM, Bennett CM, Neufeld EJ, Fuhlbrigge RC, Zurakowski D, Sundel RP. 2007. Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. J Pediatr 150: 376-82. *Shared first-authorship
  
• St. Clair NE, Kim CC, Semrin G, Woodward AL, Liang MG, Glickman JN, Leichtner AM, Binstadt BA. 2006. Celiac disease presenting with chilblains in an adolescent girl. Pediatr Dermatol 23: 451-4.
  
• Binstadt BA, Levine JC, Nigrovic PA, Gauvreau K, Dedeoglu F, Fuhlbrigge RC, Weindling SN, Newburger JW, Sundel RP. 2005. Coronary artery dilation among patients presenting with systemic-onset juvenile idiopathic arthritis. Pediatrics 116: e89-93.
  
• Almond CSD, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA, Duncan CN, Olson DP, Salerno AE, Newburger JW, Greenes DS. 2005. Hyponatremia among runners in the Boston Marathon. N Engl J Med 352:1550-6.
  
• Binstadt BA, Fleegler EW. 2005. Perforated appendicitis in a child with Henoch-Schönlein purpura. J Pediatr Surg 40: e24-27.
  
• Binstadt BA, Caldas AM, Turvey SE, Stone KD, Weinstein HJ, Jackson J, Fuhlbrigge RC, Sundel RP. 2003. Rituximab therapy for multisystem autoimmune diseases in pediatric patients. J Pediatr 143: 598-604.