Rheumatology: Current Research
Open Access
ISSN: 2161-1149 (Printed)
ISSN: 2161-1149 (Printed)
Timothy B. Niewold
Scientific Tracks Abstracts: Rheumatology & Orthopedics
I nterferon alpha (IFN-�?±) is a critical mediator of human systemic lupus erythematosus (SLE). Many lines of evidence support a primary role for IFN-�?± in the initiation of human SLE. IFN-�?± functions in viral immunity at the interface of innate and adaptive immunity, a position well-suited to setting thresholds for autoimmunity. Some individuals treated with IFN-�?± for chronic viral infections develop de novo SLE, which frequently resolves when IFN-�?± is withdrawn. These case reports suggest that IFN-�?± was causal. When circulating IFN-�?± levels are examined in SLE families, abnormally high IFN-�?± levels are found in both healthy and affected members, suggesting that high serum IFN-�?± is a heritable risk factor for SLE. Additionally, SLE-risk genetic variants in the IFN-�?± pathway are gain-of-function in nature, resulting in either higher circulating IFN-�?± levels or greater sensitivity to IFN-�?± signaling in SLE patients. A recent genome-wide association study has identified additional novel genetic loci associated with high serum IFN-�?± in SLE patients. These data support the idea that genetically determined endogenous elevations in IFN-�?± predispose to human SLE. It is possible that some of these gain-of-function polymorphisms in the IFN-�?± pathway are useful in viral defense, and that risk of SLE is a burden we have taken on in the fight to defend ourselves against viral infection.
A human geneticist and translational researcher, Dr. Niewold is a physician-scientist who plays a vital role at the Knapp Center as a ?bridge? over the traditional gap between the basic and clinical sciences. He sees patients in clinic, and actively recruits blood samples which are studied in his laboratory. His laboratory efforts focus on identifying and understanding the pathogenic factors in human lupus and autoimmune disease. This work is done entirely with human samples, studying in vivo human disease. Dr. Niewold is recognized for important contributions to our understanding of how genes influence pathogenic cytokine patterns that give rise to human lupus. This work embraces human heterogeneity, and will allow personalized intervention in this complex disease in which ?one size fits all? treatment strategies frequently fail. A native of Illinois, Dr. Niewold earned his medical degree from the University of Illinois at Chicago. He completed his internal medicine residency at the Mayo Clinic, and then focused on lupus at Cornell?s Mary Kirkland Center for Lupus Research. He was recruited to the Knapp Center in 2007, and he currently directs the Federation of Clinical Immunology Societies Center of Excellence at University of Chicago