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.

Education
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

Other Activities
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.

Memberships
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.

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.

Recent Publications

* Ramos PS, Oates JC, Kamen DL, Williams AH, Gaffney PM, Kelly JA, Kaufman KM, Kimberly RP, Niewold TB, Jacob CO, Tsao BP, Alarcón GS, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, James JA, Guthridge JM, Merrill JT, Boackle SA, Freedman BI, Scofield RH, Stevens AM, Vyse TJ, Criswell LA, Moser KL, Alarcón-Riquelme ME, Langefeld CD, Harley JB, Gilkeson GS. Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry. J Rheumatol 2013. [Abstract] EPub

Kurien BT, Dsouza A, Igoe A, Lee YJ, Maier-Moore JS, Gordon T, Jackson M, Scofield RH. Immunization with 60 kD Ro peptide produces different stages of pre-clinical autoimmunity in a Sjogren's syndrome-model among multiple strains of inbred mice. Clin Exp Immunol 2013. [Abstract] EPub

* Deng Y, Zhao J, Sakurai D, Kaufman KM, Edberg JC, Kimberly RP, Kamen DL, Gilkeson GS, Jacob CO, Scofield RH, Langefeld CD, Kelly JA, Ramsey-Goldman R, Petri MA, Reveille JD, Vila LM, Alarcon GS, Vyse TJ, Pons-Estel BA, gentine Collaborative Group, Freedman BI, Gaffney PM, Sivils KM, James JA, Gregersen PK, Anaya JM, Niewold TB, Merrill JT, Criswell LA, Stevens AM, Boackle SA, Cantor RM, Chen W, Grossman JM, Hahn BH, Harley JB, Alarcon-Riquelme ME, BIOLUPUS and GENLES Networks, Brown EE, Tsao BP. MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus. PLoS Genet 9:e1003336, 2013. [Abstract]

Selected Publications

Dillon S, Aggarwal R, Harding JW, Li LJ, Weissman MH, Li S, Cavett JW, Sevier ST, Ojwang JW, D'Souza A, Harley JB, Scofield RH. Klinefelter's syndrome (47,XXY) among men with systemic lupus erythematosus. Acta Paediatr 100:819-823, 2011. [Abstract]

* Lessard CJ, Adrianto I, Kelly JA, Kaufman KM, Grundahl KM, Adler A, Williams AH, Gallant CJ, Marta E.Alarcon-Riquelme on behalf of the BIOLUPUS and GENLES Networks, Anaya JM, Bae SC, Boackle SA, Brown EE, Chang DM, Criswell LA, Edberg JC, Freedman BI, Gregersen PK, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Park SY, Petri MA, Pons-Estel BA, Ramsey-Goldman R, Reveille JD, Song YW, Stevens AM, Tsao BP, Vila LM, Vyse TJ, Yu CY, Guthridge JM, Bruner GR, Langefeld CD, Montgomery C, Harley JB, Scofield RH, Gaffney PM, Moser KL. Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study. Am J Hum Genet 88:83-91, 2011. [Abstract]

Kurien BT, Porter A, Dorri Y, Iqbal S, D'Sousa A, Singh A, Asfa S, Cartellieri M, Mathias K, Matsumoto H, Bachmann M, Hensley K, Scofield RH. Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren's syndrome or systemic lupus erythematosus in BALB/c mice. Free Radic Biol Med 50:1222-1233, 2011. [Abstract]

Aggarwal R, Namjou B, Li S, D'Souza A, Tsao BP, Bruner BF, James JA, Scofield RH. Male-only systemic lupus. J Rheumatol 37:1480-1487, 2010. [Abstract]

Cooney CM, Bruner GR, Aberle T, Namjou-Khales B, Myers LK, Feo L, Li S, D'Souza A, Ramirez A, Harley JB, Scofield RH. 46,X,del(X)(q13) Turner's syndrome women with systemic lupus erythematosus in a pedigree multiplex for SLE. Genes Immun 10:478-481, 2009. [Abstract]

Scofield RH, Bruner GR, Namjou B, Kimberly RP, Ramsey-Goldman R, Petri M, Reveille JD, Alarcón GS, Vila LM, Reid J, Harris B, Li S, Kelly JA, Harley JB. Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: Support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 58:2511-2517, 2008. [Abstract]

Arthritis & Clinical Immunology Research Program, MS 38
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-7061
Fax: (405) 271-7063
E-mail: Hal-Scofield@omrf.org

Mollie Rangnow
Administrative Assistant

Skyler Dillon
Affiliate

Sherry Hubbell
Senior Research Technician

Biji Kurien, Ph.D.
Affiliate