Biographical Sketch

Dr Rowley performed her undergraduate studies at Colgate University in Hamilton, NY where she received a BA in chemistry summa cum laude.  She then attended medical school at SUNY Upstate Medical School in Syracuse, NY.  After graduation in 1985 she performed a pediatrics residency at Children's Hospital of Pittsburgh followed by a pediatric infectious disease fellowship at Children's Memorial Hospital in Chicago.  She then completed postdoctoral research training in the Department of Medicine at Northwestern University.   Dr. Rowley is currently an Attending Physician in the Infectious Diseases Division of Children's Memorial Hospital as well as being a Professor of Pediatrics and of Microbiology-Immunology.

Research Description

My laboratory focuses on the study of Kawasaki Disease, an acute vasculitis of young childhood that is the most common cause of acquired heart disease in developed nations and that may be fatal. Clinical and epidemiologic features of the illness support an infectious cause. Our goal is to understand the etiology and pathogenesis of the illness.

Research Abstract

The long-term goal of my laboratory is to understand the pathogenesis of Kawasaki Disease, an acute, potentially fatal vasculitis of young childhood which has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the US and other developed nations. The illness is manifested by prolonged high fever, rash, redness of the eyes and lips, puffiness of the hands and feet, and cervical adenopathy. Although these symptoms are self-limited, 20-25% of untreated patients develop coronary artery aneurysms three to six weeks after the illness. These children are at risk for aneurysm rupture, myocardial infarction, and sudden death.

In Kawasaki Disease, the blood vessel wall, particularly the coronary artery wall, is infiltrated by inflammatory cells. We discovered that IgA plasma cells infiltrate the arterial wall in acute Kawasaki Disease, and that CD8 T lymphocytes and macrophages are also present. The clinical and epidemiologic features of the illness suggest an infectious cause, and the presence of IgA plasma cells and CD8 T lymphocytes in the inflammatory infiltrate supports the hypothesis of a mucosal portal of entry and an intracellular pathogen such as a virus.

We examined the clonality of the IgA immune response in Kawasaki Disease and reported an oligoclonal, or antigen-driven, response. We made synthetic antibodies from prevalent IgA sequences in acute Kawasaki Disease inflamed arterial tissue and demonstrated that the antibodies bind to bronchial epithelium in Kawasaki Disease children but not controls, and to a subset of macrophages in acute Kawasaki Disease inflamed tissues such as the coronary artery. Light and electron microscopy revealed that the antigen detected by Kawasaki Disease synthetic antibodies in ciliated bronchial epithelial cells resides in cytoplasmic inclusion bodies that are consistent with aggregates of viral proteins and nucleic acids. Future goals are to determine the exact components of the inclusion bodies. We are also interested in identifying molecules that may be important in aneurysm formation such as tissue proteases, cytokines, and other proteins, with the ultimate goal of interfering with the host immune response which may be responsible for coronary artery damage.

Publications

Rowley AH, Shulman ST, Mask CA, Finn LS, Terai M, Baker SC, Galliani CA, Takahashi K, Naoe S, Kalelkar MB, Crawford SE. IgA plasma cell infiltration of proximal respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease. The Journal of Infectious Diseases, 2000; 182:1183-1191.

Rowley AH, Shulman ST, Spike BT, Mask CA, Baker SC.  Oligoclonal IgA response in the vascular wall in acute Kawasaki Disease.  The Journal of Immunology 2001; 166:1334-1343.

Brown TJ, Crawford SE, Cornwall M, Garcia F, Shulman ST, Rowley AH. CD8+ T-cells and Macrophages Infiltrate Coronary Artery Aneurysms in Acute Kawasaki Disease. The Journal of Infectious Diseases 2001; 184:940-3.

Gavin PJ, Crawford SE, Shulman ST, Garcia F, Rowley AH. Systemic Arterial Expression of Matrix Metalloproteinases-2 and 9 in Acute Kawasaki Disease. Atherosclerosis, Thrombosis, and Vascular Biology, 2003, 23:576-581.

Rowley AH, Baker SC, Shulman ST, Garcia FL, Guzman-Cottrill JA, Chou P, Terai M, Kawasaki T, Kalelkar MB, Crawford SE. Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki Disease by use of synthetic antibody. The Journal of Infectious Diseases 2004; 190:856-865.

Rowley AH, Baker SC, Shulman ST, Fox LM, Takahashi K, Garcia FL, Crawford SE, Chou P, Orenstein JM. Cytoplasmic Inclusion Bodies are Detected by Synthetic Antibody in Ciliated Bronchial Epithelium during Acute Kawasaki Disease. The Journal of Infectious Diseases, 2005; 192:1757-1766.

Rowley AH, Shulman ST, Garcia FL, Guzman-Cottrill JA, Miura M, Lee HL, Baker SC. Cloning the Arterial IgA Antibody Response during Acute Kawasaki Disease. The Journal of Immunology, 2005; 175: 8386-8391.

Rowley AH, Baker SC, Shulman ST, Garcia FL, Fox LM, Kos IM, Crawford SE, Russo PA, Hammadeh R, Takahashi K, Orenstein JM. RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki Disease. PLoS ONE 2008; 3: e1582.

Rowley AH, Baker SC, Orenstein JM, Shulman ST. Searching for the cause of Kawasaki disease—cytoplasmic inclusion bodies provide new insight. Nature Reviews Microbiology 2008; 6: 394-401.