Dolores Njoku joined the Johns Hopkins Department of Anesthesiology as a 5-year training fellow in the combined Pediatric Anesthesiology/Pediatric Critical Care Program in 1992 and never left. Now she is an Assistant Professor in the Division of Pediatric Anesthesiology and conducting research in the field of drug-induced, immune-mediated liver injury. It has been known for some time that certain drugs can elicit autoimmune reactions, but the mechanisms have eluded investigators for years. This situation began to change in 2005, when Dr. Njoku published her work with a mouse model that can be used reliably to mimic such drug reactions in the liver.
Some of the drugs thought to be capable of causing immune-mediated liver injury include antibiotics, anti-seizure medications, nonsteroidal anti-inflammatory drugs, and halogenated anesthetics. As an anesthesiologist, Dr. Njoku’s interest in this field originated because some patients who had undergone anesthesia for surgical procedures, as well as some physicians who were chronically exposed to halogenated anesthetic, became ill following these seemingly different types of exposures. Symptoms included fatigue, rash, and elevation of liver enzymes. With her animal model of sensitization to proteins that are affected by anesthetics, Dr. Njoku has begun to better understand the pathways involved in the injury process and recognizes that this model can also uncover pathways involved with other drugs that cause similar liver injury.
During the metabolic process, some drugs produce haptens, which can bind to and alter proteins in the liver. This alteration can result in those proteins no longer being identified by the body as “self,” and consequently, an immune reaction develops. As part of her research, Dr. Njoku analyzes a bank of serum samples from patients to look for protein-specific autoantibodies. From this investigation, she began to suspect that immunoglobulin G4 (IgG4) might be involved in the injury process. By testing this hypothesis, she found that mice that lacked the IgG4 pathway did not develop the anesthetic-induced liver disease.
In future work, Dr. Njoku hopes to uncover the immunogenic epitopes, or pieces, of the proteins that trigger the autoimmune reaction and identify the key regulatory pathways involved. The goal is to study and characterize the pathway further so that new drugs can be developed that do not trigger the disease process. One final aim would be to determine why women are more prone to develop this drug-induced, immune-mediated liver injury than are men.
- American Society of Anesthesiologists Joint Council on In-Training Examinations (2002)
- Junior Editor, American Board of Anesthesiology
- Junior Oral Board Examiner, American Board of Anesthesiology (2007)
- Njoku DB, Mellerson JL, Talor MV, Kerr DR, Faraday NR, Outschoorn I, Rose NR. Role of CYP2E1 IgG4 subclass antibodies and complement in the pathogenesis of idiosyncratic drug induced hepatitis. Clin Vaccine Immunol 13(2):258–65, 2006.
- Fairweather D, Frisancho-Kiss S, Njoku DB, Nyland JF. Kaya Z, Yusung SA, Davis SE, Frisancho A, Barrett M, Rose NR. Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1beta, and immune complex deposition in the heart. J Immunol176(6):3516–24, 2006.
- Frisancho-Kiss S, Nyland JF, Davis SE, Barrett MA, Gatewood SJ, Njoku DB, Cihakova D, Silbergeld EK, Rose NR and Fairweather D. Cutting Edge: T Cell Ig Mucin-3 reduces inflammatory heart disease by increasing CTLA-4 during innate immunity. J Immunol176(11):6411–15, 2006.
- Anderson JS, Rose NR, Martin JL, Eger EI and Njoku DB. Desflurane hepatitis associated with hapten and autoantigen-specific IgG4 antibodies. Anesth Analg 104 (6):1452, 2007.
- Nguyen C, Rose NR and Njoku DB. Trifluoroacetylated IgG4 antibodies in a child with idiosyncratic acute liver failure following first exposure to halothane. J Pediatr Gastroenterol Nutr 47(2):199–202, 2008.
- Njuoku DB, Li Z, Washington ND, Mellerson JL, Talor MV, Sharma R, Rose NR. Suppressive and pro-inflammatory roles for IL-4 in the pathogenesis of experimental drug-induced liver injury. Eur J Immunol 39(6):1652–63, 2009.
Zhaoxia Li, MD, PhD – senior postdoctoral fellow
Nicole Washington – student
- Young Investigator Award for best scientific presentation, Society of Pediatric Anesthesia (1998)
- Best Scientific Abstract of Meeting – 73rd Clinical and Scientific Congress, Intl. Anesthesia Research Society (1999)
- Best Abstract of Meeting, Cell/Tissue Damage and the Autoimmune Response Colloquium – American Autoimmune Related Diseases Association (2007)