Overview

Research Areas (IRP Lab Groups)

Current management of patients with SLE is usually stratified by the degree of internal organ involvement; treatment strategies include a variety of immunosuppressive medications, used alone or in combination, that are limited both in their efficacy and by significant potential toxicities. There is an unmet need for improved treatment of inflammation in this patient population. The all-cause mortality in SLE has greatly improved but there is significant morbidity and increased mortality due to accelerated atherosclerotic vascular disease. Further, premature cardiovascular disease risk may be as high as 50-fold when compared to matched controls and is not explained by the traditional risk factors. The underlying pathogenic mechanisms involved in endothelial dysfunction leading to premature atherosclerosis in lupus remain elusive. Advances in immunosuppression and close monitoring of patients have decreased organ damage in lupus, but no drug to this date has proven to abrogate atherosclerosis development in SLE. Identifying a drug that has immunomodulatory effects and is also vasculo-protective is an unmet need in this disease.

The Lupus Clinical Research Program at NIAMS conducts innovative translational and clinical research into the causes, treatment, and prevention of SLE. The Lupus Clinical Research Program maintains a comprehensive clinical database of SLE patients that includes patient demographics, SLE disease activity and damage indices, patient-reported outcome tools, and other data for phenotyping our cohort. The SLE Natural History and Pathogenesis protocol serves as a pivotal resource for understanding and characterizing the heterogeneity of this disease, providing biological specimens and outstanding clinical phenotyping to various intramural and extramural labs involved in lupus research. This collaborative research model has led to several biomarker discoveries and scientific hypothesis generation. These discoveries have been translated into clinical trials by the Lupus Clinical Trials Unit.

The Lupus Clinical Trials Unit (LCTU) of the Lupus Clinical Research Program develops and implements clinical research protocols and conducts high impact, innovative clinical research based largely on the discoveries resulting from NIAMS IRP translational research.

Current Projects

  • Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus; a Phase Ib Clinical Trial and Associated Mechanistic Studies.
  • The Role of PPAR-gamma Agonists in immunomodulation and Vascular Prevention in SLE (PPAR-SLE).
  • Natural history of vascular damage and atherosclerosis development in SLE.
  • Deep immuno-phenotyping and systematic study of serum proteins and gene expression in SLE.
  • Aerobic Exercise in Women with Systemic Lupus Erythematosus (Exercise SLE).
  • Genomic Effects of Glucocorticoids in Patients with Systemic Lupus Erythematosus.

Quality Improvement

Quality improvement (QI) is a framework used in health care to improve patient care, outcomes, and the development of health care professionals. It has been shown to improve morbidity and mortality. The LCTU has implemented several QI projects for our patient cohort.

  • A health maintenance section has been incorporated into all progress notes to touch on areas affected by SLE and the drugs that treat this disease. 
  • Patients with lupus are at a higher risk of osteoporosis because of chronic inflammation and the adverse effects of therapeutic medications, including glucocorticoids. We are working together with an interdisciplinary team to implement a standardized template for outpatient visits that incorporates osteoporosis assessment and management guidelines.
  • A specific sun protection brochure was created and provided to patients as education regarding SLE and photosensitivity.
  • Reproductive health is an important topic and should be a shared decision-making process between SLE patients and providers. We are currently working on implementing reproductive health counseling during patient visits.
  • Patient-reported outcome surveys are completed at every visit to help clinicians better understand the patient's perceived health status and empower the patient in their health care process.

For more information, please contact Jun Chu (Jun.Chu2@nih.gov).

DC Lupus Consortium

In 2016, The Lupus Clinical Research Program established The DC Lupus Consortium (DCLC), a collaborative network of rheumatologists, nephrologists, physiatrists, and other health care providers interested in lupus clinical research in the Metropolitan DC area. The purpose of the DCLC is to promote partnerships and referrals to the NIAMS Lupus Clinical Research Program and collaborations with local and regional clinicians caring for patients with lupus.

NIH scientists, researchers, patient advocacy groups, and physicians both within and outside of NIH are welcome to join. To learn more about upcoming DCLC events, please contact Elaine Poncio (elaine.poncio@nih.gov) or Isabel Ochoa (ochoai@mail.nih.gov) to be added to the mailing list.

DCLC 2019

Poster for the 25th Aniiversary DCLC event, showing a holwling wolf illustrationFor over 25 years, the NIH has yielded a vast wealth of knowledge about this disease and made great strides in lupus clinical research. To recognize the accomplishments and milestones, a special 25th-anniversary event at the fourth annual meeting of the DCLC featured perspectives from research participants and presentations of current and future lupus research activities at the NIH.

Montage of photos of speakers from the DCLC 2019 event.

Join Us for the Next DCLC

NIH scientists, researchers, patient advocacy groups, and physicians both within and outside of NIH are welcome to join this consortium. If you would like to learn more about upcoming DCLC events, please contact Elaine Poncio (elaine.poncio@nih.gov) or Isabel Ochoa (ochoai@mail.nih.gov) to be added to the mailing list.

Clinical Trials

RECRUITING

Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome

ClinicalTrials.gov Identifier: NCT04496960

Sjogren's syndrome (SS) is a systemic autoimmune disease that often involves multiple organs of the body. The disease primarily affects females and manifests as inflammation and destruction of glands leading to dryness of mouth, eyes, skin, throat, and vagina. Additionally, patients may experience profound fatigue, widespread muscle pain, and swollen and painful joints. Researchers are trying to find new, more effective, and safe treatments for SS. The objective of this study is to evaluate the safety and tolerability of tofacitinib, an oral janus kinase inhibitor, in people with SS.


RECRUITING

Natural History of Coronavirus Disease (COVID-19) in Systemic Autoimmune Diseases

ClinicalTrials.gov Identifier: NCT04690816

Viral infections such as COVID-19 may lead to flare-ups in people with systemic autoimmune diseases (SAD). These infections may also change the function of their immune system and/or cause problems with their blood vessels. Researchers want to learn how people with SAD respond to treatments or vaccines for COVID-19. The objective of this study is to understand how COVID-19 affects inflammation, the immune system, and blood vessels in adults and children with autoimmune diseases.


RECRUITING

Vascular Study of Lupus Patients

ClinicalTrials.gov Identifier: NCT00001372

Patients with Lupus have an increased risk of developing heart attacks and stroke due to hardening of the arteries (atherosclerosis). By examining how your blood vessels function and whether they are damaged and by comparing these tests to those of patients without Lupus, we will be able to better understand what triggers this complication in lupus and hopefully identify potential strategies to prevent this damage. During this study, it is possible that we will obtain an unanticipated finding about your health during the imaging studies. An example of an unanticipated finding would be a nodule, abnormality, or cancer in your colon, lungs, or other areas of your body seen on the imaging studies. We can provide you this information to take to your doctor if there is/are any findings on the scans. The procedures include Blood, urine, PET/CT scan, CT Heart scan, Cardiac MRI, Vascular procedures (EndoPat/CAVI/Sphygmocor testings). You will need to fast for most of the day for scans, water is ok to drink. Individual participation requires 2-3 visits to the NIH Clinical Center and 1 follow-up phone call to explaining the results of the scans.


RECRUITING

Vascular Study of Healthy Volunteers

ClinicalTrials.gov Identifier: NCT00001372

We are examining how blood vessels function and how these vessels damaged due to lupus disease activities. We compare the data to see what the blood vessels should be as healthy person such as you but due to the Lupus disease activities how it changed compare to a healthy volunteer on the same age and gender. During this study, it is possible that we will obtain an unanticipated finding about your health during the imaging studies. An example of an unanticipated finding would be a nodule, abnormality, or cancer in your colon, lungs, or other areas of your body seen on the imaging studies. We can provide you this information to take to your doctor if there is/are any findings on the scans. Thank you for your contribution as healthy volunteer to make a difference and better understand the Lupus Vascular Study. The procedures include Blood, urine, PET/CT scan, CT Heart scan, Cardiac MRI, Vascular procedures (EndoPat/CAVI/Sphygmocor testings). You will need to fast for most of the day for scans, water is ok to drink. Individual participation requires 2-3 visits to the NIH Clinical Center and 1 follow-up phone call to explaining the results of the scans.


RECRUITING

Genomic Effects of Glucocorticoids in Patients with Systemic Lupus Erythematosus

ClinicalTrials.gov Identifier: NCT04233164

This is a study of the acute effects of glucocorticoids (also commonly called “steroids”) on the immune system of patients with SLE. Participants will receive a single intravenous (IV) infusion of methylprednisolone sodium succinate (steroid infusion). The main purpose of this study is to better understand how glucocorticoids (steroids) change the way the body reads genes. This information may be helpful for developing new and better drugs for treating SLE that have the same benefits as glucocorticoids (steroids) but without the side effects. Individual participation requires 2 visits to the NIH Clinical Center and 2 follow-up phone calls.


RECRUITING

Natural History of SLE

ClinicalTrials.gov Identifier: NCT00001372

This study follows a group of individuals over time who have SLE. The goals are:

  • Most importantly to do various research studies to find out what causes SLE and gather clinical information relating to the natural history of the disease, comorbid conditions, and complications related to the disease treatment.
  • To follow patients during the course of the disease to understand how the disease changes over time and the effects of standard treatments.
  • To evaluate patients thought to have the disease to better understand how the disease begins and how it affects patients.
  • To determine eligibility for specific research protocols involving patients with SLE requiring a separate informed consent.
  • To obtain biologic specimens to be used in laboratory-based studies of the pathogenesis of SLE, including genetic studies and be used in laboratory-based studies of the pathogenesis of SLE from healthy volunteers.

Scientific Publications

Selected Recent Publications

Changes in cardiorespiratory function and fatigue following 12 weeks of exercise training in women with systemic lupus erythematosus: a pilot study.

Hasni S, Feng LR, Chapman M, Gupta S, Ahmad A, Munday A, Mazhar MA, Li X, Lu S, Tsai WL, Gadina M, Davis M, Chu J, Manna Z, Nakabo S, Kaplan MJ, Saligan L, Keyser R, Chan L, Chin LMK
Lupus Sci Med.
2022 Oct;
9(1).
doi: 10.1136/lupus-2022-000778
PMID: 36220328

Use of gonadotropin-releasing hormone agonists for ovarian preservation in patients receiving cyclophosphamide for systemic lupus erythematosus: A meta-analysis.

Ejaz K, Abid D, Juneau P, Chu J, Hasni S
Lupus.
2022 Dec;
31(14).
doi: 10.1177/09612033221128740
PMID: 36148853

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

Hasni S, Temesgen-Oyelakin Y, Davis M, Chu J, Poncio E, Naqi M, Gupta S, Wang X, Oliveira C, Claybaugh D, Dey A, Lu S, Carlucci P, Purmalek M, Manna ZG, Shi Y, Ochoa-Navas I, Chen J, Mukherjee A, Han KL, Cheung F, Koroleva G, Belkaid Y, Tsang JS, Apps R, Thomas DE, Heller T, Gadina M, Playford MP, Li X, Mehta NN, Kaplan MJ
Ann Rheum Dis.
2022 Aug 1;
81(11).
doi: 10.1136/ard-2022-222658
PMID: 35914929

Long-term follow-up after lymphodepleting autologous haematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus.

Goklemez S, Hasni S, Hakim FT, Muraro PA, Pirsl F, Rose J, Memon S, Fowler DF, Steinberg SM, Baker EH, Panch SR, Gress R, Illei GG, Lipsky PE, Pavletic SZ
Rheumatology (Oxford).
2022 Aug 3;
61(8).
doi: 10.1093/rheumatology/keab877
PMID: 34875023

Clinical Images: Cardiovascular magnetic resonance to detect and monitor inflammatory myocarditis in systemic lupus erythematosus.

Pamuk ON, Bandettini WP, Vargha J, Shanbhag SM, Hasni S
ACR Open Rheumatol.
2022 Feb;
4(2).
doi: 10.1002/acr2.11364
PMID: 34791837

Risk Factors for COVID-19 and Rheumatic Disease Flare in a US Cohort of Latino Patients.

Fike A, Hartman J, Redmond C, Williams SG, Ruiz-Perdomo Y, Chu J, Hasni S, Ward MM, Katz JD, Gourh P
Arthritis Rheumatol.
2021 Jul;
73(7).
doi: 10.1002/art.41656
PMID: 33455077

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

Aringer M, Brinks R, Dörner T, Daikh D, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL, Jayne D, Cervera R, Costedoat-Chalumeau N, Diamond B, Gladman DD, Hahn B, Hiepe F, Jacobsen S, Khanna D, Lerstrøm K, Massarotti E, McCune J, Ruiz-Irastorza G, Sanchez-Guerrero J, Schneider M, Urowitz M, Bertsias G, Hoyer BF, Leuchten N, Schmajuk G, Tani C, Tedeschi SK, Touma Z, Anic B, Assan F, Chan TM, Clarke AE, Crow MK, Czirják L, Doria A, Graninger W, Halda-Kiss B, Hasni S, Izmirly PM, Jung M, Kumánovics G, Mariette X, Padjen I, Pego-Reigosa JM, Romero-Diaz J, Rúa-Figueroa Í, Seror R, Stummvoll GH, Tanaka Y, Tektonidou MG, Vasconcelos C, Vital EM, Wallace DJ, Yavuz S, Meroni PL, Fritzler MJ, Naden R, Costenbader K, Johnson SR
Ann Rheum Dis.
2021 Jun;
80(6).
doi: 10.1136/annrheumdis-2020-219373
PMID: 33568386

Bite of the wolf: innate immune responses propagate autoimmunity in lupus.

Gupta S, Kaplan MJ
J Clin Invest.
2021 Feb 1;
131(3).
pii: 144918. doi: 10.1172/JCI144918
PMID: 33529160

LOX-1: A potential driver of cardiovascular risk in SLE patients.

Sagar D, Gaddipati R, Ongstad EL, Bhagroo N, An LL, Wang J, Belkhodja M, Rahman S, Manna Z, Davis MA, Hasni S, Siegel R, Sanjuan M, Grimsby J, Kolbeck R, Karathanasis S, Sims GP, Gupta R
PLoS One.
2020;
15(3).
doi: 10.1371/journal.pone.0229184
PMID: 32182251

Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus.

Smith MA, Chiang CC, Zerrouki K, Rahman S, White WI, Streicher K, Rees WA, Schiffenbauer A, Rider LG, Miller FW, Manna Z, Hasni S, Kaplan MJ, Siegel R, Sinibaldi D, Sanjuan MA, Casey KA
Sci Rep.
2020 Mar 10;
10(1).
doi: 10.1038/s41598-020-60563-9
PMID: 32157125

Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus.

Mistry P, Nakabo S, O'Neil L, Goel RR, Jiang K, Carmona-Rivera C, Gupta S, Chan DW, Carlucci PM, Wang X, Naz F, Manna Z, Dey A, Mehta NN, Hasni S, Dell'Orso S, Gutierrez-Cruz G, Sun HW, Kaplan MJ
Proc Natl Acad Sci U S A.
2019 Dec 10;
116(50).
doi: 10.1073/pnas.1908576116
PMID: 31754025

Key Publications

Long-term follow-up after lymphodepleting autologous hematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus.

Goklemez S, Hasni S, Hakim FT, Muraro PA, Pirsl F, Rose J, Memon S, Fowler DF, Steinberg SM, Baker EH, Panch SR, Gress R, Illei GG, Lipsky PE, Pavletic SZ
Rheumatology (Oxford).
2021 Dec 7;
pii: keab877. doi: 10.1093/rheumatology/keab877
PMID: 34875023

Risk Factors for COVID-19 and Rheumatic Disease Flare in a US Cohort of Latino Patients.

Fike A, Hartman J, Redmond C, Williams SG, Ruiz-Perdomo Y, Chu J, Hasni S, Ward MM, Katz JD, Gourh P
Arthritis Rheumatol.
2021 Jul;
73(7).
doi: 10.1002/art.41656
PMID: 33455077

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus.

Hasni SA, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Carlucci PM, Wang X, Naqi M, Playford MP, Goel RR, Li X, Biehl AJ, Ochoa-Navas I, Manna Z, Shi Y, Thomas D, Chen J, Biancotto A, Apps R, Cheung F, Kotliarov Y, Babyak AL, Zhou H, Shi R, Stagliano K, Tsai WL, Vian L, Gazaniga N, Giudice V, Lu S, Brooks SR, MacKay M, Gregersen P, Mehta NN, Remaley AT, Diamond B, O'Shea JJ, Gadina M, Kaplan MJ
Nat Commun.
2021 Jun 7;
12(1).
doi: 10.1038/s41467-021-23361-z
PMID: 34099646

Lupus-like autoimmunity and increased interferon response in patients with STAT3-deficient hyper-IgE syndrome.

Goel RR, Nakabo S, Dizon BLP, Urban A, Waldman M, Howard L, Darnell D, Buhaya M, Carmona-Rivera C, Hasni S, Kaplan MJ, Freeman AF, Gupta S
J Allergy Clin Immunol.
2021 Feb;
147(2).
doi: 10.1016/j.jaci.2020.07.024
PMID: 32768442

Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism.

Gupta S, Nakabo S, Blanco LP, O'Neil LJ, Wigerblad G, Goel RR, Mistry P, Jiang K, Carmona-Rivera C, Chan DW, Wang X, Pedersen HL, Gadkari M, Howe KN, Naz F, Dell'Orso S, Hasni SA, Dempsey C, Buscetta A, Frischmeyer-Guerrerio PA, Kruszka P, Muenke M, Franco LM, Sun HW, Kaplan MJ
Proc Natl Acad Sci U S A.
2020 Jul 14;
117(28).
doi: 10.1073/pnas.2003603117
PMID: 32601182

LOX-1: A potential driver of cardiovascular risk in SLE patients.

Sagar D, Gaddipati R, Ongstad EL, Bhagroo N, An LL, Wang J, Belkhodja M, Rahman S, Manna Z, Davis MA, Hasni S, Siegel R, Sanjuan M, Grimsby J, Kolbeck R, Karathanasis S, Sims GP, Gupta R
PLoS One.
2020;
15(3).
doi: 10.1371/journal.pone.0229184
PMID: 32182251

2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.

Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL, Jayne D, Cervera R, Costedoat-Chalumeau N, Diamond B, Gladman DD, Hahn B, Hiepe F, Jacobsen S, Khanna D, Lerstrøm K, Massarotti E, McCune J, Ruiz-Irastorza G, Sanchez-Guerrero J, Schneider M, Urowitz M, Bertsias G, Hoyer BF, Leuchten N, Tani C, Tedeschi SK, Touma Z, Schmajuk G, Anic B, Assan F, Chan TM, Clarke AE, Crow MK, Czirják L, Doria A, Graninger W, Halda-Kiss B, Hasni S, Izmirly PM, Jung M, Kumánovics G, Mariette X, Padjen I, Pego-Reigosa JM, Romero-Diaz J, Rúa-Figueroa Fernández Í, Seror R, Stummvoll GH, Tanaka Y, Tektonidou MG, Vasconcelos C, Vital EM, Wallace DJ, Yavuz S, Meroni PL, Fritzler MJ, Naden R, Dörner T, Johnson SR
Arthritis Rheumatol.
2019 Sep;
71(9).
doi: 10.1002/art.40930
PMID: 31385462

Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti-IgE Monoclonal Antibody in Systemic Lupus Erythematosus.

Hasni S, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Joyal E, Fike A, Manna Z, Auh S, Shi Y, Chan D, Carlucci P, Biehl A, Dema B, Charles N, Balow JE, Waldman M, Siegel RM, Kaplan MJ, Rivera J
Arthritis Rheumatol.
2019 Jul;
71(7).
doi: 10.1002/art.40828
PMID: 30597768

Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases.

Gupta S, Tatouli IP, Rosen LB, Hasni S, Alevizos I, Manna ZG, Rivera J, Jiang C, Siegel RM, Holland SM, Moutsopoulos HM, Browne SK
Arthritis Rheumatol.
2016 Jul;
68(7).
doi: 10.1002/art.39607
PMID: 26815287

News & Highlights

Spotlight on Research | November 23, 2021

New treatment shows promise in reducing the risk of cardiovascular disease in people with lupus

Researchers have identified a potential treatment to reduce the risk of cardiovascular disease in people with systemic lupus erythematosus (SLE), a chronic autoimmune disease.
Featured | March 26, 2021

Dr. Sarfaraz Hasni Receives 2021 Coleman Research Innovation Award

We are delighted to announce that Sarfaraz Hasni, M.D., Director of the NIAMS Lupus Clinical Trials Unit, has received the 2021 William G. Coleman Jr., Ph.D., Minority Health and Health Disparities Research Innovation Award.