Overview

Vasculitis is a family of rare diseases defined by inflammation in blood vessels. These conditions, if not quickly recognized and properly treated, can cause serious and life-threatening damage to multiple organ systems. The goal of the Vasculitis Translational Research Program (VTRP) is to discover factors that cause vasculitis and to develop novel ways for physicians to diagnose and monitor these diseases more effectively.

Tremendous progress over the last few decades has transformed vasculitis from frequently fatal into a chronic, manageable illness. However, treatment with potentially toxic medications, including steroids and other medications that suppress the immune system, is generally required to induce remission. Although most patients with vasculitis achieve remission with treatment, the majority of patients experience one or more recurrences of the disease. Disease relapse can result in additional permanent organ damage and can be fatal. At present, we have a very crude understanding of what causes vasculitis. There are very few tests available that reliably help a doctor predict which patients will experience a relapsing disease course. The identification of factors that cause vasculitis and the discovery of biomarkers that can predict clinical outcomes and guide patient-specific therapeutic decisions is the major focus of the VTRP.

The VTRP was established in 2013 to evaluate patients with known vasculitis or with clinical suspicion of vasculitis. Diseases of interest include Takayasu’s arteritis (TAK), relapsing polychondritis (RP), giant cell arteritis (GCA), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and polyarteritis nodosa (PAN) among other types of vasculitis.

Current Projects

A selection of our current projects are as follows:

VEXAS Syndrome

Image
A section of an illustration of a body with VEXAS symptoms against a background showing neutrophils.

VEXAS syndrome is a disease that leads to inflammatory and hematologic (blood) manifestations. It is caused by mutations in the UBA1 gene of blood cells and acquired later in life.

Discover more about this syndrome, how it is diagnosed, who gets it, and the work currently being done by the Vasculitis Translational Research Program to better understand and treat it.

Vascular Imaging in Large-Vessel Vasculitis

Three images visualizing vasculitis in a patient.
Vascular imaging including FDG-PET (left) and magnetic resonance angiography are useful to evaluate vascular inflammation and damage in patients with large-vessel vasculitis.

Takayasu’s arteritis and giant cell arteritis are the two major diseases that affect the aorta and its primary branches. The detection of active vasculitis is important to prevent the progression of vascular disease and organ damage; however, clinical assessment of disease activity is challenging. Although vascular imaging is considered essential in these diseases, there are no accepted guidelines for imaging and prospective imaging data is lacking. Our group has employed advanced molecular imaging techniques in patients with large-vessel vasculitis to study whether serial imaging has diagnostic and prognostic value in addition to monitoring utility. We discovered that the majority of patients with large-vessel vasculitis have evidence of ongoing vascular inflammation by FDG-PET scans during periods of apparent clinical remission and that the degree of vascular inflammation seen during clinical remission predicts future relapse. We developed and validated PETVAS, a quantitative measure of vascular inflammation that is being used internationally as an outcome measure in ongoing clinical trials. Our lab is working to define a potential immunologic basis for subclinical inflammation in these conditions.

Relapsing Polychondritis

Three images visualizing vasculitis in a patient.
Using data-driven classification, we identified three subgroups of patients with relapsing polychondritis based on pattern of organ involvement.

Our group recently established the largest prospective cohort of relapsing polychondritis. The NIH RP program currently has recruited >100 patients with relapsing polychondritis. Patients are evaluated at 6-month intervals using a standardized assessment protocol with biobanking of research samples. From these efforts, we have published some of the only observational cohort data in relapsing polychondritis. Using latent class analysis, we have defined three major clinical subsets of RP based on the pattern of organ involvement. and are using these subsets as the framework to investigate causal disease factors, treatment approaches, and potential biomarkers. Recently, in collaboration with the Kastner lab, we have discovered a genetic factor that is causal in 8% of patients with relapsing polychondritis.

Neutrophil Biology in Small and Medium-Vessel Vasculitis

Color image of neutrophil traps
Neutrophil extracellular traps (NETs) are the by-product of a specific form of cell death. NETs are immunogenic, toxic to the vasculature, and play a role in many forms of vasculitis. In this photo, NETs (long pink strands) are triggered by adenosine in a patient with vasculitis.

Neutrophils are key cells that drive inflammation in many forms of vasculitis. Our group has partnered with the Kaplan Lab in the Systemic Autoimmunity Branch to study novel aspects of neutrophil biology and innate immune system involvement in ANCA-associated vasculitis, drug-induced vasculitis, and monogenic vasculitis. Through these efforts, we have learned that a subset of neutrophils known as low-density granulocytes may play a pathogenic role in ANCA-associated vasculitis, that cholinergic receptors on neutrophils mediate disease in levamisole-induced vasculitis, and that the adenosine-mediated activation of neutrophils contributes to inflammation in deficiency in deaminase 2 (DADA2).

Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

Image & Media Gallery

Clinical Trials

RECRUITING

Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis

ClinicalTrials.gov Identifier: NCT02257866

Vasculitis is a group of diseases that inflame and damage blood vessels and tissue. It can cause many medical problems. Few tests can diagnose the disease, and none can reliably predict a relapse. Researchers want to study people's genes and follow people over time to see how the disease affects them. The objective of this clinical trial is to learn the signs, symptoms, imaging tests, genetic markers, and blood tests that can help identify people with vasculitis and predict what will happen to them over time. Patients enrolled in this protocol will undergo a history, physical examination, and laboratory evaluation. 

 


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.

Scientific Publications

Selected Recent Publications

Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.

Ferrada MA, Savic S, Cardona DO, Collins JC, Alessi H, Gutierrez-Rodrigues F, Kumar DBU, Wilson L, Goodspeed W, Topilow JS, Paik JJ, Poulter JA, Kermani TA, Koster MJ, Warrington KJ, Cargo C, Tattersall RS, Duncan CJA, Cantor A, Hoffmann P, Payne EM, Bonnekoh H, Krause K, Cowen EW, Calvo KR, Patel BA, Ombrello AK, Kastner DL, Young NS, Werner A, Grayson PC, Beck DB
Blood.
2022 Sep 29;
140(13).
doi: 10.1182/blood.2022016985
PMID: 35793467

Association of (18) F-Fluorodeoxyglucose-Positron Emission Tomography Activity With Angiographic Progression of Disease in Large Vessel Vasculitis.

Quinn KA, Ahlman MA, Alessi HD, LaValley MP, Neogi T, Marko J, Novakovich E, Grayson PC
Arthritis Rheumatol.
2023 Jan;
75(1).
doi: 10.1002/art.42290
PMID: 35792044

VEXAS Syndrome and Disease Taxonomy in Rheumatology.

Grayson PC, Beck DB, Ferrada MA, Nigrovic PA, Kastner DL
Arthritis Rheumatol.
2022 Nov;
74(11).
doi: 10.1002/art.42258
PMID: 35696333

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis.

Suppiah R, Robson JC, Grayson PC, Ponte C, Craven A, Khalid S, Judge A, Hutchings A, Merkel PA, Luqmani RA, Watts RA, DCVAS Study Group
Arthritis Rheumatol.
2022 Mar;
74(3).
doi: 10.1002/art.41983
PMID: 35106973

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis.

Grayson PC, Ponte C, Suppiah R, Robson JC, Craven A, Judge A, Khalid S, Hutchings A, Luqmani RA, Watts RA, Merkel PA, DCVAS Study Group
Arthritis Rheumatol.
2022 Mar;
74(3).
doi: 10.1002/art.41982
PMID: 35106968

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis With Polyangiitis.

Robson JC, Grayson PC, Ponte C, Suppiah R, Craven A, Judge A, Khalid S, Hutchings A, Watts RA, Merkel PA, Luqmani RA, DCVAS Study Group
Arthritis Rheumatol.
2022 Mar;
74(3).
doi: 10.1002/art.41986
PMID: 35106964

Mutant UBA1 and Severe Adult-Onset Autoinflammatory Disease. Reply.

Beck DB, Grayson PC, Kastner DL
N Engl J Med.
2021 Jun 3;
384(22).
doi: 10.1056/NEJMc2102124
PMID: 34077654

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.

Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC
Arthritis Rheumatol.
2021 Oct;
73(10).
doi: 10.1002/art.41743
PMID: 33779074

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America.

Goel R, Gribbons KB, Carette S, Cuthbertson D, Hoffman GS, Joseph G, Khalidi NA, Koening CL, Kumar S, Langford C, Maksimowicz-McKinnon K, McAlear CA, Monach PA, Moreland LW, Nair A, Pagnoux C, Quinn KA, Ravindran R, Seo P, Sreih AG, Warrington KJ, Ytterberg SR, Merkel PA, Danda D, Grayson PC
Rheumatology (Oxford).
2020 May 1;
59(5).
doi: 10.1093/rheumatology/kez421
PMID: 31580452

Diagnostic Assessment Strategies and Disease Subsets in Giant Cell Arteritis: Data From an International Observational Cohort.

Gribbons KB, Ponte C, Craven A, Robson JC, Suppiah R, Luqmani R, Watts R, Merkel PA, Grayson PC
Arthritis Rheumatol.
2020 Apr;
72(4).
doi: 10.1002/art.41165
PMID: 31729185

Clinical symptoms and associated vascular imaging findings in Takayasu's arteritis compared to giant cell arteritis.

Michailidou D, Rosenblum JS, Rimland CA, Marko J, Ahlman MA, Grayson PC
Ann Rheum Dis.
2020 Feb;
79(2).
doi: 10.1136/annrheumdis-2019-216145
PMID: 31649025

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis.

Quinn KA, Rosenblum JS, Rimland CA, Gribbons KB, Ahlman MA, Grayson PC
Semin Arthritis Rheum.
2020 Feb;
50(1).
doi: 10.1016/j.semarthrit.2019.07.008
PMID: 31375256

Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis.

Quinn KA, Gelbard A, Sibley C, Sirajuddin A, Ferrada MA, Chen M, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Ytterberg SR, Merkel PA, Grayson PC
Rheumatology (Oxford).
2019 Dec 1;
58(12).
doi: 10.1093/rheumatology/kez217
PMID: 31199488

Patterns of Arterial Disease in Takayasu Arteritis and Giant Cell Arteritis.

Gribbons KB, Ponte C, Carette S, Craven A, Cuthbertson D, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Quinn KA, Robson JC, Seo P, Sreih AG, Suppiah R, Warrington KJ, Ytterberg SR, Luqmani R, Watts R, Merkel PA, Grayson PC
Arthritis Care Res (Hoboken).
2020 Nov;
72(11).
doi: 10.1002/acr.24055
PMID: 31444857

Key Publications

Comparing Semiquantitative and Qualitative Methods of Vascular 18F-FDG PET Activity Measurement in Large-Vessel Vasculitis.

Dashora HR, Rosenblum JS, Quinn KA, Alessi H, Novakovich E, Saboury B, Ahlman MA, Grayson PC
J Nucl Med.
2022 Feb;
63(2).
doi: 10.2967/jnumed.121.262326
PMID: 34088771

VEXAS syndrome.

Grayson PC, Patel BA, Young NS
Blood.
2021 Jul 1;
137(26).
doi: 10.1182/blood.2021011455
PMID: 33971000

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease.

Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC, Pei W, Balanda N, Ross DL, Ospina Cardona D, Wu Z, Patel B, Manthiram K, Groarke EM, Gutierrez-Rodrigues F, Hoffmann P, Rosenzweig S, Nakabo S, Dillon LW, Hourigan CS, Tsai WL, Gupta S, Carmona-Rivera C, Asmar AJ, Xu L, Oda H, Goodspeed W, Barron KS, Nehrebecky M, Jones A, Laird RS, Deuitch N, Rowczenio D, Rominger E, Wells KV, Lee CR, Wang W, Trick M, Mullikin J, Wigerblad G, Brooks S, Dell'Orso S, Deng Z, Chae JJ, Dulau-Florea A, Malicdan MCV, Novacic D, Colbert RA, Kaplan MJ, Gadina M, Savic S, Lachmann HJ, Abu-Asab M, Solomon BD, Retterer K, Gahl WA, Burgess SM, Aksentijevich I, Young NS, Calvo KR, Werner A, Kastner DL, Grayson PC
N Engl J Med.
2020 Dec 31;
383(27).
doi: 10.1056/NEJMoa2026834
PMID: 33108101

Defining Clinical Subgroups in Relapsing Polychondritis: A Prospective Observational Cohort Study.

Ferrada M, Rimland CA, Quinn K, Sikora K, Kim J, Allen C, Sirajuddin A, Goodspeed W, Chen M, Grayson PC
Arthritis Rheumatol.
2020 Aug;
72(8).
doi: 10.1002/art.41270
PMID: 32249511

Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2.

Carmona-Rivera C, Khaznadar SS, Shwin KW, Irizarry-Caro JA, O'Neil LJ, Liu Y, Jacobson KA, Ombrello AK, Stone DL, Tsai WL, Kastner DL, Aksentijevich I, Kaplan MJ, Grayson PC
Blood.
2019 Jul 25;
134(4).
doi: 10.1182/blood.2018892752
PMID: 31015188

News & Highlights

NIH News in Health | June 6, 2022

Understanding Autoimmune Diseases

Sometimes, your immune system makes mistakes. If it sees your body’s healthy cells as a threat, it may attack them. This can cause an autoimmune disorder.
Spotlight on Research | November 4, 2020

NIH Researchers Discover a New Inflammatory Disease Called VEXAS

NIH scientists led an international team of researchers toward discovery of a new, adult-onset inflammatory disease abbreviated the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.