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Research Interests
The immune system distinguishes self from non-self. In autoimmunity, this ability fails. My research concentrates on the systemic autoimmune diseases, systemic lupus erythematosus and Sjögren's syndrome, which are characterized by a loss of tolerance to the ubiquitous antigens Ro/SSA and La/SSB. We use a wide range of scientific disciplines, from clinical research to laboratory-based basic research to animal models of human disease.
Presently we are studying a powerful genetic linkage on chromosome 11 at p13 that is found in families with severe SLE that are ethnically identified as Black Americans. Both a candidate gene approach as well as high density single nucleotide polymorphism typing are underway. Once an allele is identified, then the mechanism by which SLE susceptibility is increased will be explored. The etiology for the preponderance of women with SLE is under study. We have found that Klinefelter's syndrome (male 47, XXY) is found in excess in SLE. Genetic linkage on X is established and is being further defined to test the hypothesis of a gene dose effect. Other genetic interests include the relationship of prolidase deficiency to systemic autoimmunity.
My laboratory is also interested in the immunology of systemic lupus erythematosus and Sjögren's syndrome. Immunization of animals with short peptides from 60 kD Ro induces epitope spreading as well as a Sjögren's syndrome-like illness. The immunology and genetics of this model are being explored. Future studies of this model will include adoptive transfer, genetic control of epitope spreading as well as disease manifestations, MRI imaging of animals, and prevention by dendritic cell immunization.
Human lupus is being studied at the level of B cell immunity, including antibodies binding superoxide dismutase. This project complements the animal immunization studies in that oxidatively modified antigens induce enhanced epitope spreading. We also find that humans with SLE have more oxidative modification of proteins and lipids than do controls.
Clinical research involving diabetes is also ongoing. In one project the metabolic effects of glucosamine, a nutripharmaceutical given for osteoarthritis, are studied. Preliminary data demonstrate worsening insulin resistance in human taking oral glucosamine in doses recommended for osteoarthritis. We are now investigating mechanism and long term effects. A second project focused on glucose control after bone marrow transplant. A retrospectoive study shows elevated glucose is associated with 5-fold more infections, a longer hosptal stay and increased mortality. A prospective trial of intensive glucose control is underway.
Education
| 1989-1991 |
Associate Research Scientist, Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK |
| 1988-1991 |
Fellow, Section of Endocrinology, Metabolism and Hypertension, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, OK |
| 1987-1988 |
Chief Medical Resident, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, OK |
| 1984-1987 |
Resident in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, OK |
| 1980-1984 |
MD - University of Texas Southwestern Medical School, Dallas, TX |
| 1976-1980 |
BA - Chemistry, Texas A&M University, College Station, TX |
Scofield RH, Bruner GR, Kelly J, Harley JB. Klinefelter’s Syndrome, 47,XXY Among Men with Systemic Lupus Erythematosus suggests a gene dose effect on the X chromosome. Arthritis Rheum, in press.
Kamen DL, Shaftman SR, Barron M, Parker TM, Bruner GR, Aberle T, James JA, Scofield RH, Harley JB, Gilkeson GS, Autoantibody Prevalence and Lupus Disease Characteristics in a Unique African American Population. Arthritis Rheum, in press.
Kurein BT, D’sousa A, Rodgers R, Shenoi J, Kurono S, Matsumoto H, Asfa S, Hensley K, Scofield RH. Detection of catalase as a major protein target of the lipid peroxidation product 4-HNE and the association of a polymorphism in its promoter region as a risk factor in SLE, revisions requested and submitted.
Mosallaei-Benjamin M, Hamadani S, Scofield RH, Selby GB. Elevated serum glucose during bone marrow transplant predicts outcome. Bone Marrow Transplant, revision requested.
Sawalha AH, Webb R, Han S, Kelly JA, Kaufman KM, Kimberly RP, Alarcón-Riquelme ME, James JA, Vyse TJ, Gilkeson G, Choi C-B, Scofield RH, Bae S-C, Nath SK, Harley JB. Common variants within MECP2 confer risk of systemic lupus erythematosus. PloS ONE, in press.
Malik S, Bruner GR , Williams-Weese C, Feo L, Scofield RH, Reichlin M, Harley JB, Sawalha AH. The presence of anti-La autoantibody is associated with a lower risk of nephritis and seizures in lupus patients. Lupus 16:863-866, 2007 (PMID: 17971358).
Pham T, Scofield RH. 13-cis-retinoic acid induction of clinical polycystic ovarian disease. Endocr Prac 13:776-779, 2007 (PMID: 18194936).
Tauseef A, Greenfield RA, Scofield RH, Bronze MS. Gatifloxacin –Associated Hypoglycemia. J Okla St Med Assoc 100:425-428, 2007.
Blevins S, Leyva, MJ, Wright JE, Scofield RH, Aston CE. Effect of Cinnamon on Glucose and Lipid Levels in Non-insulin Dependent Type 2 Diabetes Mellitus. Diabetes Care 30:2236-2237, 2007 (PMID: 17563345).
Pham T, Cornea A, Blick KE, Jenkins A, Scofield RH. Oral glucosamine in doses used to treat osteoarthritis worsens insulin resistance. Am J Med Sci, 333:333-339, 2007 (PMID 17570985).
Kurien BT, Scofield RH. Four men in a space station - to say nothing of the cow!: the quest for finding respite and work in the ultimate frontier. Med Hypotheses, 68:1195-1199, 2007 (PMID: 17306929).
Kurien BT, Scofield RH. Can low dose diagnostic dental radiation trigger Sjögren's syndrome?
Medical Hypotheses, 69:995-1000, 2007 (Epub 2007 Apr 17) (PMID: 17442501).
Kurien BT, Scofield RH. Curcumin/tumeric solubilized in sodium hydroxide inhibits HNE protein modification. J Ethnopharmacol 110:368-373, 2007.
Kamble S, Kem D, Baker MZ, Scofield H, Lyons T, Olansky L. Thymic neuroendocrine tunor presenting as Cushing’s syndrome: A case report and review of current literature. EndoTrends 14:10-11, 2007.
Scofield RH, Bruner GR, Harley JB, Namjou B. Autoimmune thyroid disease is associated with secondary Sjögren’s syndrome in familial systemic lupus. Ann Rheum Dis 66:41-413, 2007 (Epub August 24, 2006 at http://ard.bmjjournals.com)
Addington S, Larsen N, Scofield RH. Milk-alkali syndrome in pre-eclamptic pregnancy. J Okla St Med Assoc 99:480-484, 2006.
Scofield RH. Poor, Poor Thing. Blood and Thunder: Musing on the Art of Medicine. 6:106-108, 2006.
Wang, H., Kurien, B.T., Lundgreen, D., Patel, N.C., Kaufman, K.M., Miller, D.S., Porter, A.C., D’Sousa, A., Nye, L., Tumbush, J., Kerr, D.S., Kurono, S., Matsumoto, H., Scofield, R.H. A Nonsense Mutation Of PEPD In Four Amish Children With Prolidase Deficiency. Am J Med Genet 140:580-5, 2006.
Poole BD, Scofield RH, Harley JB, James JA. Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus. Autoimmunity 39:63-70, 2006.
Kurien, B.T., Patel, N.C., Porter, A.C., Miller, D., D’Sousa, A., Matsimoto, H., Heng, W., Scofield, R.H. Prolidase Deficiency and Biochemical Assays Used In Its Diagnosis. Anal Biochem, revisions requested.
Beall DP, Henslee HB, Webb HR, Scofield RH. Milk-alkali syndrome: a historical review and description of the modern version of the syndrome. Am J Med Sci. 331:233-42, 2006.
Kurien BT, Singh A, Matsumoto H, Scofield RH. Improving the solubility and pharmacological efficacy of curcumin by heat treatment. Assay Drug Dev Technol. 5:567-576, 2007 (PMID: 17767425).
Kurien BT, Scofield RH. Lipid peroxidation in SLE. Indian J Exp Biol 44:349-356, 2006. (PMID: 16708886).
Kurien BT, Patel NC, Porter AC, Miller D, D’Sousa A, Matsimoto H, Wang H, Scofield RH. Proidase deficiency and biochemical assays used in its diagnosis. Anal Biochem 349:165-175, 2006 (PMID: 16298326).
Kurien BT, Scofield RH. Autoantibody determination in the diagnosis of systemic lupus erythematosus. Scand J Immunol 64:227-235, 2006 (PMID: 16918691).
Reviews and Invited Papers
Kurien BT, Scofield RH. Autoimmune diseases and oxidatively modified autoantigens Autoimmunity Rev, in press.
Mathews SA, Kurien BT, Scofield RH. Oral manifestations of Sjögren’s syndrome. J Dent Res 87:308-318, 2008.
Scofield RH. Autoimmune hypo- and hyperthyroid in systemic autoimmune disease. In, Walker SE, Jara LJ, eds, Handbook of Systemic Autoimmune Diseases 9:195-205, 2008.
Williams PH, Cobb BL, Namjou B, Scofield RH, Sawalha AH, Harley JB. Horizons in Sjögren's Syndrome Genetics. Clin Rev Allergy Immunol 32:201-209, 2007 (Epub ahead of print 26 Oct 2007) (PMID: 17963047)
Kurien BT, Scofield RH. Western Blotting. Methods 38:283-293, 2006. (PMID: 16483794)
Kurien BT, Hensley K, Bachmann M, Scofield RH. Oxidatively modified autoantigens in autoimmune diseases. Free Rad Biol Med 41:549-556, 2006.
James JA, Harley JB, Scofield RH. Epstein Barr virus and Systemic Lupus Erythematosus. Curr Opin Rheumatol 18:462-467, 2006.
Kurien BT, Scofield RH. Lipid peroxidation in SLE. Indian J Exp Biol 44:349-356, 2006.
Kurien BT, Patel NC, Porter AC, Miller D, D’Sousa A, Matsimoto H, Wang H, Scofield RH. Proidase deficiency and biochemical assays used in its diagnosis. Anal Biochem 349:165-175, 2006.
Kurien BT, Scofield RH. Autoantibody determination in the diagnosis of systemic lupus erythematosus. Scand J Immunol 64:227-235, 2006.
Beall DP, Henslee HB, Webb HR, Scofield RH. Milk alkali syndrome: Historical review and description of the modern version of the syndrome. Am J Med Sci 331:233-242, (PMID: 16702792) 2006.
Poole BD, Scofield RH, Harley JB, James JA. Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus. Autommunity 39:1-8, 2006.
Books Chapters and Manuscripts
Zacharias L, Scofield RH. Rheumatic Manifestations of Systemic Disease. In, Lohr KM,
Talavera F, Brent LH, Plantz SH, Zevitz ME, eds, Textbook of Medicine (emedicine.com),
2006.
Reichlin, M, Scofield, RH. Ro (SS-A) antibodies. In: Shoenfeld Y, Gershwin ME, and Meroni PL, eds, Textbook of Autoantibodies, 2nd ed, (Elsevier:Amsterdam), 2006.
Scofield RH. Milk-alkali syndrome. In, Pourmotabbed G, Talavera F, Khardori R, Cooper
M, Griffing GT, eds, Medicine Specialties: Endocrinology (emedicine.com), 2006.
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