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ARRA Investments in Autoimmune Rheumatic and Skin Diseases


Public Health Burden
Autoimmune diseases result from the immune system—the body’s protective mechanisms against pathogens—attacking its own cells and tissues. These attacks are often mediated by autoantibodies, which recognize the body’s own molecules, and other molecules of the immune system. Autoimmune rheumatic and skin diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (lupus), and psoriasis, are debilitating, chronic, inflammatory diseases that collectively affect more than seven million American adults and children.

Diagnosis and Disease Monitoring
Symptoms and disease course vary widely within RA, lupus, and other rheumatic disease patient populations. Diagnosis and prediction of patient outcomes are hampered by the complexity of these illnesses. Biomarkers are naturally-occurring molecules that offer insights into a person’s risk for a disease, as well as characteristics of a patient’s disease, its progress, and its response to treatment. Biomarker discovery and validation are active areas of research and the topic of several ARRA-funded projects, such as:
  • Analysis of autoantibodies and other immune system molecules that may be used for early diagnosis of RA and determination of disease severity to enable early treatment before irreversible tissue damage occurs, and so appropriate therapies can be matched to individual patients.1
  • Identification of inflammation-associated molecules and lupus-specific autoantibodies, for disease classification, to predict disease risk, and guide the management of individual patients’ conditions.2
  • Use of a biospecimen repository, created by a nationwide network of clinical researchers studying inflammatory diseases of blood vessels, or vasculature, for discovery of biomarkers to measure and predict disease activity, and response to therapy.3
Treatment
A wide range of effective drugs for RA have become available in recent years; however, some patients are not responsive to these therapeutic agents, and some may suffer toxic side effects from certain treatments. The nascent field of pharmacogenomics research, which studies how the individual patient’s genome influences responses to drugs, is expected to have a tremendous impact on the development and selection of tailored treatments that are targeted and effective. Examples include:
  • Establishment of a collaborative network and essential infrastructure for pharmacogenomics research in RA, to launch a database and biorepository as a critical resource for the larger RA research community4. This will become a platform for elucidating the molecular basis of the disease and finding effective treatments for RA patients.
  • Creation of tools for comparative effectiveness and cost-effectiveness research of treatments for RA5 and psoriasis6, with the aim of creating more rational treatment decisions and improved patient care.
  • Development of novel pharmacologic inhibitors of a critical enzyme involved in immune cell dysregulation, which may be effective in the treatment of autoimmune diseases, such as RA and lupus7.
Basic Research
Although some treatments are available for autoimmune rheumatic and skin diseases, not all patients respond to them. As well, there are still many unknown factors concerning disease risk and progression. To support the development of more diagnostic and therapeutic approaches, NIH ARRA funds also support fundamental research projects, such as:
  • Genome analysis and genetic fine-mapping to identify disease susceptibility genes among patients with psoriasis8 and lupus9, with particular attention to differences between lupus patients from various ethnic groups.
  • Examination of altered gene products from psoriasis patients for understanding aberrant pathways and identifying candidate therapeutic targets10.
  • Elucidation of immune cell processes in autoimmune diseases11, potential triggers of aberrant immune cell reactions in RA12, and possible developmental and genetic causes of immune cell dysregulation in autoimmune diseases13.
  • Investigation of the connections between nervous and immune system function in situations of sleep restriction, resulting in amplified immune reactivity in an animal model of arthritis14.
  • Examination of the molecular and cellular communications involved in the occurrence of atherosclerosis (plaque build-up in arteries, commonly called “hardening of the arteries”) in RA patients, which can cause early mortality15.



  1. 1RC1AR058713-01 -- Proteomic Identification of Actionable Biomarkers in Rheumatoid Arthritis -- Robinson, William (CA)
  2. 1RC1AR058554-01, -- Predicting Systemic Autoimmunity through Follow-up of Blood Relatives -- James, Judith (OK); 1-RC1-AR058817-01 -- High Throughput Screening of the Autoimmune Epitome -- Karp, David (TX) (contact), Kodadek, Thomas (FL), Olsen, Nancy (TX)
  3. 1RC1AR058303-01, Identification and Validation of Biomarkers for Vasculitis, Merkel, Peter (contact), Monach, Paul (MA)
  4. 1RC2AR058964-01, Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository, Bridges, S. Louis (AL)
  5. 1RC1AR058601-01, -- Clinical and Cost-effectiveness of Biologics in Rheumatoid Arthritis, Choi, Hyon (MA); 1-RC2-AR058989-01 -- Randomized Observation Study of Biologic Therapy for Rheumatoid Arthritis -- Moreland, Larry (contact), Levesque, Marc (PA)
  6. 1RC1AR058204-01 -- Comparative Effectiveness of Biologics for Psoriasis -- Gelfand, Joel (PA)
  7. 1RC2AR058947-01 -- An Allosteric Inhibitor of ZAP-70 as a Novel Therapeutic for Autoimmune Disease -- Weiss, Arthur (CA)
  8. 1RC1AR058315-01 -- Genotyping the NPF Biobank for Psoriasis Susceptibility Genes -- Elder, James (MI)
  9. 1RC1AR058621-01, -- Identification of Susceptibility Genes for SLE of Amerindian Origin in Hispanics -- Alarcon-Riquelme, Marta (OK); 1RC2AR058959-01 -- Candidate Causal Variants in Systemic Lupus Erythematosus -- Gaffney, Patrick (contact) (OK), Wakeland, Edward (TX).
  10. 1RC1AR058681-01 -- Systems Biology of Psoriasis -- Bowcock, Anne (contact), Zhang, Weixiong (MO)
  11. 1RC2AR059010-01 -- Transcriptome and Epigenome Analysis of Helper T Cell Specification and Plasticity -- Dong, Chen (WA)
  12. 1RC2AR058986-01 -- Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis -- Abramson, Steven (contact), Littman, Dan (NY)
  13. 1RC2AR059092-01 -- Genes and Phenotype (GAP) Studies of Immunologic and Inflammatory Pathways -- Gregersen, Peter (contact), Diamond, Betty (NY)
  14. 1RC1AR058723-01 -- Chronic Sleep Restriction Increases Immunity to Autoantigen: Role of the SNS -- Postlethwaite, Arnold (TN)
  15. 1R21AR056786-01A1 -- MHC Class II-Associated Endothelial Dysfunction -- Holoshitz, Joseph (MI)


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