Studying childhood stroke to better understand inflammatory diseases

2014

Challenge

The immune system plays a very important function, protecting us against viruses, bacteria, and other disease-causing pathogens. Autoinflammatory diseases cause the immune system to malfunction, resulting in unprovoked inflammation that can lead to fevers and other dangerous symptoms. Researchers do not yet have a full understanding of these diseases’ underlying genetic mechanisms.

Advance

IRP scientists led by Massimo Gadina, Ph.D., Qing Zhou, Ph.D., Dan Yang, M.D., Manfred Boehm, M.D., Daniel L. Kastner, M.D., Ph.D., and Ivona Aksentijevich, M.D., studied the occurrence of stroke in young children and showed that a genetic mutation leading to the absence of a white blood cell protein, ADA2, in blood plasma results in inflammation and vascular anomalies.

Impact

The team’s finding advances understanding of how white blood cells regulate immune response to pathogens and keep inflammation under control. Their results also help scientists understand the genetic basis of inflammatory and vascular diseases, aiding in the development of targeted treatment strategies. 

Publications

Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffmann P, Negro A, Tsai WL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CC, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinun M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I. (2014). Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 370(10), 911-20.