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Robert H. “Hal” Scofield, M.D.

Member
Arthritis & Clinical Immunology Research Program

Adjunct Associate Professor, Department of Pathology and Department of Medicine, University of Oklahoma Health Sciences Center

My 101

Normally the immune system protects the body from harmful bacteria and viral infections. But in autoimmune diseases, the immune system turns against the body, causing weakness, pain, and organ dysfunction, and sometimes leads to premature death.

In my laboratory, we’re working toward a better understanding autoimmune disease. In general autoimmune disease effects women much more commonly than men. For instance, 90% of lupus and Sjögren’s syndrome patients are women. That is, men are 10 times less likely to have these diseases than women. The sex chromosome are X and Y – women have two X chromosomes, while men have an X and a Y. However, we have found that men with an extra X chromosome, which occur in about 1 in 500 male births, have some autoimmune diseases at the same rate as women. In addition, women with three X chromosomes also have increased risk of autoimmune disease. We are now exploring the molecular and genetic basis by which an extra X chromosomes gives risk of autoimmunity.

We’re also looking at the genetics and immunology of both systemic lupus erythematosus, more often called just lupus, and the related Sjögren’s syndrome. We’re interested in how these diseases differently affect ethnic groups such as Native and African Americans. African Americans are more likely to have lupus and to have more severe cases of the disease, while Native Americans are more likely to have Sjögren’s syndrome. We are studying how antibodies, usually made to fight against viruses and bacteria, may cause these autoimmune diseases.

In conjunction with the US Department of Veterans Affairs, we have recently begun a project to examine autoimmune disease among those with post-traumatic stress disorder. Those with PTSD have 2 or 3 times more lupus, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid disease then those with PTSD.  We’re studying how the immune system is abnormal in PTSD patients.

Research

My laboratory studies the immunology, genetics and clinical expression of the autoimmune diseases systemic lupus erythematosus and Sjögren’s syndrome. Like most autoimmune disease, lupus and Sjögren’s predominately affect women, with ~90% of patients being female. For years those interested in lupus and Sjögren’s asked why women have these diseases. A few years ago we reversed the question and asked why some men get lupus or Sjögren’s. In order to facilitate answering such a question, we collected the largest cohort of men with lupus ever assembled as well as large group of men with Sjögren’s. We found that among these men, Klinefelter’s syndrome (47,XXY, 1 in 500 live male births) was over-represented about 15-fold.  Klinefelter men have an extra X chromosome; that is, are 47,XXY while normal men are 46,XY. In addition, we found that women with an extra X chromosome (47,XXX, 1 in 1000 live female births) were found more than expected by chance alone among women with these diseases. In cells with more than one X chromosome, all but one is inactivated, but this in activation is not complete in that some X chromosome genes escape inactivation. We are now studying the molecular and immunological basis of the X chromosome dose effect. These studies concentrate on genes on the X chromosome that escape inactivation and whose protein products are critical to the immune system, especially interferon production. Understanding the female bias of autoimmune disease at a fundamental level will be a critical step forward.

Antibodies are produce by the immune system against foreign invaders such as bacteria and virus. In autoimmune disease, antibodies are produced against self. We are studying how such antibodies are involved in the pathogenesis of Sjögren’s syndrome.  We produced recombinant, human monoclonal antibodies from B lymphocytes purified from the salivary glands of Sjögren’s patients.  In this way we can study the disease causing potential of these auto-antibodies. Our results indicate that autoantibodies are produced in the salivary glands of Sjögren’s patients. These antibodies can impair saliva production perhaps by binding muscarinic receptors. In addition, unusual glycosylation of antibodies can lead to autoimmunity.

Post-traumatic stress disorder is common in the general population and is associated with an increased risk of autoimmune diseases, including lupus, rheumatoid arthritis, multiple sclerosis and thyroid disease. In a recently started project, we are studying autoantibodies as well as B lymphocytes hyperactivity in PTSD. We hypothesize that there are immune abnormalities that predispose to both PTSD and autoimmune disease. Alternatively, PSTD might induce immune alterations that then give rise to autoimmunity. Our work should be able to distinguish these two possibilities.

Infection with Epstein-Barr virus (EBV, the causative agent of mononucleosis, may be important in the genesis of lupus and Sjögren’s syndrome. We are determining whether the Epstein Barr nuclear antigen 2 (EBNA2), a genetic transcription factor, binds to genes that increase the risk of Sjögren’s syndrome. In addition, we will determine whether EBNA2 is expression salivary gland from Sjögren’s patients. These studies should develop a pathophysiological basis by which EBV infection may be permissive for development of autoimmune disease.

 

Brief CV

Education
B.A., Texas A&M University, 1980
M.D., University of Texas Southwestern Medical School, Dallas, 1984
M.A., Johns Hopkins University, Exp. 2023

Honors and Awards

Distinguished Student, Texas A&M University
1987 Stewart Wolf Award as 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
2003-2018 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
2006 Federation of Clinical Immunology Societies (FOCIS) national meeting Travel Award
2014 University of Oklahoma Board of Regents Award for Superior Creative Activity
2015 Cecil Martin Distinguished Lecturer, Southern Illinois College of Medicine
2015 Keynote Speaker, Six Southern Chinese Provinces Rheumatology Meeting, Changsha, China
2016 Keynote Speaker, Korean Rheumatology Society, Seoul, Korea
2016 Lewisville High School Hall of Fame inductee
2018 James F Hammarsten Physician of Excellence Award, Oklahoma City Department of Veterans Affairs Health Care Center
2019 Fellow, Southern Society of Clinical Investigation

Other Activities

Serves as Associate Chief of Staff for Research at the Oklahoma City Department of Veterans Affairs Medical Center; Chair, Pharmacy & Therapeutics Committee, OKC VAMC; Member, Clinical Competency Committee, internal medicine residency program, OUHSC Department of Medicine; Member, International Sjögren's Syndrome Criteria Working Group; Executive Committee and Co-Chair, Pulmonary Sub-committee Sjögren’s Syndrome Foundation/American College of Rheumatology Working Group for Sjögren’s Treatment Guidelines; Member, Publications Committee, American College of Rheumatology; volunteer physician, Good Shepard Clinic; Member, Concert and Jazz Band, New Horizons International Music Association, University of Oklahoma.

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.

Publications

View more publications

Recent Publications

Harley ITW, Allison K, Scofield RH. Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans. Front Immunol 13:953439, 2022 August, PMID: 36090990, PMCID: PMC9450536

Xu L, Zhao J, Sun Q, Xu X, Wang L, Liu T, Wu Y, Zhu J, Geng L, Deng Y, Awgulewitsch A, Kamen DL, Oates JC, Raj P, Wakeland EK, Scofield RH, Guthridge JM, James JA, Hahn BH, McCurdy DK, Wang F, Zhang M, Tan W, Gilkeson GS, Tsao BP. Loss-of-function variants in SAT1 cause X-linked childhood-onset systemic lupus erythematosus. Ann Rheum Dis, 2022 August, PMID: 35977808

Khatri B, Tessneer KL, Rasmussen A, Aghakhanian F, Reksten TR, Adler A, Alevizos I, Anaya JM, Aqrawi LA, Baecklund E, Brun JG, Bucher SM, Eloranta ML, Engelke F, Forsblad-d'Elia H, Glenn SB, Hammenfors D, Imgenberg-Kreuz J, Jensen JL, Johnsen SJA, Jonsson MV, Kvarnström M, Kelly JA, Li H, Mandl T, Martín J, Nocturne G, Norheim KB, Palm Ø, Skarstein K, Stolarczyk AM, Taylor KE, Teruel M, Theander E, Venuturupalli S, Wallace DJ, Grundahl KM, Hefner KS, Radfar L, Lewis DM, Stone DU, Kaufman CE, Brennan MT, Guthridge JM, James JA, Scofield RH, Gaffney PM, Criswell LA, Jonsson R, Eriksson P, Bowman SJ, Omdal R, Rönnblom L, Warner B, Rischmueller M, Witte T, Farris AD, Mariette X, Alarcon-Riquelme ME, PRECISESADS Clinical Consortium., Shiboski CH, Sjögren’s International Collaborative Clinical Alliance (SICCA)., Wahren-Herlenius M, Ng WF, UK Primary Sjögren’s Syndrome Registry., Sivils KL, Adrianto I, Nordmark G, Lessard CJ. Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells. Nat Commun 13:4287, 2022 July, PMID: 35896530, PMCID: PMC9329286

Selected Publications

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. 2019 Oct 21;10:2160. PMID: 31695690 PMCID: PMC6816314

Harris VM, Harley ITW, Kurien BT, Koelsch KA, Scofield RH. Lysosomal pH Is Regulated in a Sex Dependent Manner in Immune Cells Expressing CXorf21. Front Immunol. 2019 Apr 2;10:578. PMID: 31001245 PMCID: PMC6454867

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 European Americans and African Americans. Arthritis Care Res (Hoboken). 2020 Aug;72(8):1049-105 PMID: 31199565, PMCID: PMC6911033

Basu A, Izuora K, Betts NM, Kinney JW, Salazar AM, Ebersole JL, Scofield RH. Dietary Strawberries Improve Cardiometabolic Risks in Adults with Obesity and Elevated Serum LDL Cholesterol in a Randomized Controlled Crossover Trial. Nutrients. 2021 Apr 23;13(5):1421. doi: 10.3390/nu13051421. PMID: 33922576, PMCID: PMC8145532

Park EH, Ha YJ, Kang EH, Song YW, Scofield RH, Lee YJ. Baseline disease activity influences subsequent achievement of patient acceptable symptom state in Sjögren's syndrome. Rheumatology (Oxford). 2021 Jun 18;60(6):2714-2724. PMID: 33188390

Lee AS, Scofield RH, Hammitt KM, Gupta N, Thomas DE, Moua T, Ussavarungsi K, St Clair EW, Meehan R, Dunleavy K, Makara M, Carsons SE, Carteron NL; Consensus Expert Panel (CEP) Members. Consensus Guidelines for Evaluation and Management of Pulmonary Disease in Sjögren's. Chest. 2021 Feb;159(2):683-698. PMID: 33075377

Contact

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
E-mail: Hal-Scofield@omrf.org

For media inquiries, please contact OMRF’s Office of Public Affairs at news@omrf.org.

Lab Staff

Christina Bruxvoort
Graduate Student

Martha Tsaliki
Graduate Student

Joshua Cavett
Affiliate

Ambre Chambers
Affiliate

Katie Cusack
Affiliate

Biji Kurien
Affiliate

Valerie Lewis, Ph.D.
Affiliate

Dashari Miller
Affiliate

Ann Elizabeth Tebow
Affiliate

Stephanie Lawrence
Affiliate

 

News from the Scofield lab

From pandemic to endemic
October 24, 2021

This past week, the seven-day national average of new Covid-19 cases reached its lowest levels since late July.

Should we fear Covid variants?
June 29, 2021

A Covid-19 variant that appears more contagious than the earliest strain of the virus is increasingly circulating in the U.S. But is the mutation something to fear?

Coping with re-entry anxiety
June 8, 2021

After more than a year of masks, physical distancing and staying home, more than half of U.S. adults have experienced anxiety about returning to in-person interactions.

Is the coronavirus here to stay?
June 11, 2020

Even after the pandemic subsides, the coronavirus is likely to join the list of contagious diseases that remain in circulation for decades to come.

Are Oklahomans at risk for EEE virus?
October 25, 2019

A dangerous mosquito-borne virus making the news recently is EEE, or Eastern Equine Encephalitis. Should Oklahomans take precations?

Is stomach ‘flu’ really the flu?
January 16, 2019

More accurately called gastroenteritis, contagious stomach illness is most often caused by two viruses, rotavirus or norovirus.

Governor declares April Sjögren’s syndrome awareness month in Oklahoma
April 2, 2009

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 […]

National Conference on Sjogren’s Syndrome to be Held in Oklahoma City
October 23, 1998

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 […]