Research Highlights
The William S. Rowe Division of Rheumatology at Cincinnati Children's Hospital Medical Center is committed to research which will help with the diagnosis and treatment for children with rheumatic diseases. Supported by Foundations and the National Institute of Health, there are numerous research protocols in the division. Research studies are often performed in collaboration with other national and international research organizations.
Systemic Onset Juvenile Rheumatoid Arthritis is Associated With Natural Killer (NK) Cell Function Abnormalities
Systemic Onset Juvenile Rheumatoid Arthritis (SoJRA) and an associated condition known as Macrophage Activation Syndrome (MAS) are severe and often devastating illnesses. The pathological mechanisms are not known but Alexei Grom, MD, has focused his research approach on NK and cytotoxic cell function in this disease. The rationale for this approach has been based on the strong clinical similarities between MAS and the better understood autosomal recessive disorder familial hemophagocytic lymphohistiocytosis (FHLH), in which the uncontrolled proliferation of T cells and macrophages has been recently associated with decreased NK cell and cytotoxic cell functions secondary to mutations in the gene encoding perforin. Recent observations suggest as in FHLH, MAS patients also have profoundly depressed NK function. Moreover, a large subgroup of SoJRA patient has very similar immunologic abnormalities. Combined with the evidence of the immunoregulatory role of NK cells in many immune responses, this suggests that NK dysfunction is relevant to the pathogenesis of MAS. New directions have thus been established for research in this poorly understood disease.
New Biologic Treatments for Juvenile Rheumatoid Arthritis Offer Hope
Although rheumatic diseases are rare, they affect approximately 300,000 children in the United States. The most common is juvenile rheumatoid arthritis (JRA), touching the lives of 70,000 children nationally. New immune response modifiers offer new hope for improving the quality of life for children with chronic rheumatic diseases. In Pediatric Rheumatology, at Cincinnati Children's Hospital Medical Center researchers are working to find the new biologic drugs and combination of therapies that may be able to put these children into a state of permanent remission. Daniel Lovell, MD, MPH, and Edward Giannini, MSc, DrPH, are coordinating these prospective multicenter and often multinational studies. One of the drugs they previously tested is called Enbrel" and is now being prescribed to several hundred of children in the United States. At Cincinnati Children's, an international leader in designing and conducting clinical trials in pediatric rheumatology, they will follow children through puberty and into adulthood, monitoring and reporting on any side effects of Enbrel". Drs. Lovell and Giannini lead the Pediatric Rheumatology Collaborative Study Group, composed of almost 100 arthritis centers in North America with affiliated with European centers.
To aid research in JRA worldwide, Dr. Giannini led the creation of standardized criteria to measure improvement in patients with JRA. Known as the American College of Rheumatology (ACR) Pediatric 30, these standards were adopted by the ACR in 2002 and allow researchers to compare treatments and results across all clinical trials. For his contributions to the field of rheumatology, Dr. Giannini was honored in 2002 with the National Arthritis Foundation's Virginia P. Engalitcheff Award for Impact on the Quality of Life. Current research focuses on identifying the most effective combinations of biologic therapies with traditional drug therapies has not been well studied. Because of the profound effectiveness of these treatments in controlling the disease, investigators are now thinking about induction of remission both on and off medications as a very real and possible outcome. However, no studies have been done to assess the practicality of this approach.
Finding the Genes That Cause Juvenile Rheumatoid Arthritis
Juvenile rheumatoid arthritis (JRA) is an autoimmune disease categorized as a complex genetic trait. Our genetic studies have identified both HLA and non-HLA candidate genes and several chromosome regions for potential contribution to either JRA susceptibility or resistance. Together, the existing collection of DNA from the JRA Affected Sib Pair Registry, and a cohort of more than 600 simplex JRA families, the developments of the Human Genome Project and technical advances in SNP genotyping to identify JRA genes has become possible. Under the leadership of David Glass, MD, and Susan Thompson, PhD, studies of gene expression patterns to use as new markers of disease are being performed. These expression markers may provide a molecular basis for treatment decisions at early stages of disease. By integrating our results on JRA gene expression with those of JRA genetic analyses and the use of novel computational methods we will increase the understanding in the biological pathways and processes that underlie JRA.
Pursuing Perfection – Research in the Improvement of Patient Care
Since 2002, the Division of Rheumatology has been a participant in the Pursuing Perfection Program of the Cincinnati Children's Hospital Medical Center. Murray Passo, MD, and Janalee Taylor, RN, MSN, CNS, are the Divisional leaders of this endeavor. Teams consisting of health-care professionals, patients and their families have been focused on improving outcomes for children with Juvenile Rheumatoid Arthritis (JRA) and other rheumatic disease. Research done at the Rheumatology Clinic identified key determinants affecting patient outcomes. Specific determinants include physical function, pain, health-related quality of life and self-management skills. The efforts in continuously assessing and reviewing the effectiveness of care delivered on the lives of children with rheumatic diseases have improved patient outcomes.
