Autoimmune diseases are especially frustrating, because they involve the immune system. Normally, the immune system protects the body from harmful bacteria and infections. But in autoimmune diseases, the immune system turns against the body, causing weakness and pain and sometimes leads to premature death.
In my laboratory, we’re working on three major projects. The biggest is trying to develop a new animal model of Sjögren’s syndrome. Why create an animal model of a disease? So we can learn more about the disease and find new and better treatments for patients. Sjögren’s syndrome is an autoimmune disease that targets glands that produce saliva and tears. Patients with the disease can live very painful lives, because saliva and tears play important roles in keeping our eyes and mouths clean and disease-free.
We’re also looking at the genetics of systemic lupus erythematosus, more often called just lupus, and how it affects black families. African Americans are more likely to have lupus and to have more severe cases of the disease. We’re hoping to figure out which genes play a role in the disease and how to predict and prevent the disease from occurring.
Our last focus is the correlation between lupus in men and the rare disease Klinefelter’s syndrome. Men are 10 times less likely to have lupus than women and Klinefelter’s (in which the man has an extra X chromosome) happens to only one in 17,000 men – but male lupus patients are much more likely to also have Klinefelter’s syndrome. We think this could play a role in why lupus affects women so much more frequently than men.
My laboratory concentrates on three major projects. First, we have developed a new animal model of Sjögren’s syndrome. This is a common autoimmune rheumatic illness in which there is autoimmune targeting of the salivary and lacrimal glands. Most people with the illness have antibodies in their sera binding the Ro and La proteins. When BALB/c mice are immunized with short peptides (15-18 amino acids in length) from the 60 kD Ro sequence, the mice first develop antibodies and T cell responses recognizing the peptide of immunization. Shortly thereafter there is intra- and intermolecular spreading such that these animals develop autoantibodies binding other epitopes of 60 kD Ro as well as anti-La and and anti-Ro52. We find lymphocytic infiltrates in the salivary glands of immunized animals whose structure and composition are similar to those found in the salivary glands of humans with Sjögren’s syndrome. Also, mice have a decrease in stimulated salivary flow. Thus, these mice recapitulate human Sjögren’s syndrome. Disease can be adoptively transferred by either cells or sera. Experiments are ongoing to determine the specificities of the cell type required for adoptive transfer as well as the specificity of immunoglobulin required for transfer of disease.
In regard to the genetics of SLE, my lab is pursuing the established and confirmed genetic linkage at 11q13 found in Black American SLE families. Black Americans have SLE more frequently and more severely than do White Americans. The strongest linkage is among families with severe disease. The linkage interval has been narrowed by typing of microsatellites within the region. In addition, typing of a large number of single nucleotide polymorphisms has been carried out. Several possible genetic associations are being pursued, including the catalase gene promoter region. We are also interested in the role of prolidase deficiency in autoimmunity.
Finally, we are investigating the association of SLE in men with the presence of Klinefelter’s syndrome (47,XXY). Klinefelter’s syndrome is present in 1 in 17,000 live male births, but our data indicate that 5 of 207 men with SLE have 47,XXY. Meanwhile, Turner’s syndrome (45,XO females) is not commonly found among women with SLE. Thus, we hypothesize that the female-to-male predilection of SLE is due to a gene dose effect on the X chromosome.
B.A., Texas A&M University, 1980
M.D., University of Texas Southwestern Medical School, Dallas, 1984
Honors and Awards
Distinguished Student, Texas A&M University
1987 Stewart Wolf Award
Outstanding Medicine Resident
1988-1989 W.W. Rucks Fellowship
1989-1991 Presbyterian Health Foundation Fellowship
1989 Visiting Professor’s Award
1989 Outstanding Paper, OUHSC Housestaff Scientific Session
1990 Best Paper in Internal Medicine, OUHSC Housestaff, Scientific Session
1990 Lloyd Rader Scholarship, Outstanding Postgraduate Trainee, OUHSC
1992-1997 Physician Scientist Award, NIH, Institute of Musculoskeletal and Skin Diseases
1992 The Merrick Award for Outstanding Research, OMRF
1995 Internal Medicine Faculty Teaching Award, Department of Medicine, OUHSC
1996 OUHSC Provost Award for research by an Assistant Professor
1994 Henry Christian Award, American Federation of Medical Research (national meeting)
1998 Fellow, American College of Physicians
2001 James A. Shannon Director’s Award (NIAMS and the Office for Research on Women’s Diseases)
2002 OUHSC Provost Award for research by a senior faculty member
2003-present Oklahoma Health Research Committee (appointed by Governor Brad Henry)
2004 Ethel Baxter Award for Outstanding Sjogren’s Syndrome Abstract, American College of Rheumatology National Meeting
Serves on the Medical Records Committee for University Hospital; representative to the American Federation of Clinical Research; Vice-Chairman, Research and Development Committee, Department of Veteran’s Affairs Medical Center; member of the Medical Residency Education Review Committee, Department of Medicine, OUHSC; Chairman, Institutional Review Board, OMRF; member, Research Committee, Department of Medicine, OUHSC; volunteer physician, Little Flower Clinic.
American College of Physicians
American College of Rheumatology
American Federation of Clinical Research
The Endocrine Society
American Association for the Advancement of Science
American Diabetes Association
Oklahoma Rheumatism Association
The Society of General Internal Medicine
The New York Academy of Sciences
American Association of Immunologists
Joined OMRF Scientific Staff in 1991.
Harris VM, Koelsch KA, Kurien BT, Harley ITW, Wren JD, Harley JB, Scofield RH. Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis. Front Immunol 10:2160, 2019 October, PMID: 31695690, PMCID: PMC6816314
Rasmussen A, Stone DU, Kaufman CE, Hefner KS, Fram NR, Siatkowski RL, Huang AJW, Chodosh J, Rasmussen PT, Fife DA, Pezant N, Grundahl K, Radfar L, Lewis DM, Weisman MH, Venuturupalli S, Wallace DJ, Rhodus NL, Brennan MT, Montgomery CG, Lessard CJ, Scofield RH, Sivils KL. Reproducibility of Ocular Surface Staining in the Assessment of Sjögren Syndrome-Related Keratoconjunctivitis Sicca: Implications on Disease Classification. ACR Open Rheumatol 1:292-302, 2019 July, PMID: 31453437, PMCID: PMC6710016
Scofield RH, Sharma R, Pezant N, Kelly JA, Radfar L, Lewis DM, Kaufman CE, Cioli S, Harris J, Grundahl K, Rhodus NL, Wallace DJ, Weisman MH, Venuturupalli S, Brennan MT, Koelsch KA, Lessard CJ, Montgomery CG, Sivils KL, Rasmussen A. American Indians Have A Higher Risk Of Sjögren's Syndrome And More Disease Activity Than Caucasians And African-Americans. Arthritis Care Res (Hoboken), 2019 June, PMID: 31199565
Harris VM, Sharma R, Cavett J, Kurien BT, Liu K, Koelsch KA, Rasmussen A, …, Lessard CJ, Harley JB, Sivils KL, Scofield HR. Corrigendum to "Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome." Clin Immunol. 2017 Nov 28. pii: S1521-6616(17)30854-9. PMID: 29195081
Schell J, Betts NM, Foster M, Scofield RH, Basu A. Cranberries improve postprandial glucose excursions in type 2 diabetes. Food Funct. 2017 Jul 27. [Epub ahead of print] PMID: 28748974
Li H, Reksten TR, Ice JA, ..., Scofield RH, Kovats S, Mariette X, Rönnblom L, Witte T, Rischmueller M, Wahren-Herlenius M, Omdal R, Jonsson R, Ng WF; for UK Primary Sjögren's Syndrome Registry, Nordmark G, Lessard CJ, Sivils KL. Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genet. 2017 Jun 22;13(6):e1006820. [Epub ahead of print] PMID: 28640813 PMCID: PMC5501660
Vivino FB, Carsons SE, Foulks G, Daniels TE, Parke A, Brennan MT, Forstot SL, Scofield RH, Hammitt KM. New Treatment Guidelines for Sjögren's Disease. Rheum Dis Clin North Am. 2016 Aug;42(3):531-51. Review. PMID: 27431353 PMCID: PMC5812283
Scofield RH. Sjögren Syndrome in the Twenty-First Century. Rheum Dis Clin North Am. 2016 Aug;42(3):xiii-xiv. PMID: 27431355
Arthritis & Clinical Immunology Research Program, MS 38
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7144
Fax: (405) 271-7063
News from the Scofield lab
You may never have heard of Sjögren’s syndrome, but you may very well know someone suffering from the illness. Sjögren’s (pronounced SHOW-grins) is a chronic autoimmune disease in which the body’s white blood cells attack the moisture-producing glands. The hallmark symptoms are dry eyes and dry mouth, but Sjögren’s may also cause dysfunction of other […]
In a study published tomorrow in The New England Journal of Medicine, scientists report that in patients suffering from systemic lupus erythematosus (commonly known as lupus), autoantibodies – proteins that the body mistakenly unleashes against its own tissue – are typically present years before patients are diagnosed with the disease. This research by scientists at […]
Patients who suffer with this autoimmune disease, as well as physicians who treat it, will gather in Oklahoma City Saturday, October 31 for the Ninth Annual National Conference for Sjogren’s Syndrome (NSSA). Chairman of the symposium is Morris Reichlin, M.D., Head of the Arthritis and Immunology Research Program at the Oklahoma Medical Research Foundation and […]