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          Labs @ NIAMS
          Vasculitis Translational Research Program








Vasculitis Translational Research Program


Peter Grayson, M.D., M.Sc. FacebookEmailPrintFacebookEmail
        Montage of scientific scans and scientists reviewing computer monitors.

      Overview

                                  Investigator
      
  


Peter Grayson, M.D., M.Sc.
      
  


            peter.grayson@nih.gov
      
                                                                        

  
   Research Areas (IRP Lab Groups)
          Autoimmunity,
          Clinical Research,
          Computational Biology,
          Epidemiology,
          Genetics and Genomics,
          Immunology
                                
            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 ProjectsA 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 VasculitisThree 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 PolychondritisThree 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 VasculitisColor image of neutrophil trapsNeutrophil 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).
      

                                            Scientific Advances
      
  

      August 23, 2023Mitochondria Contribute to Consequences of Giant Cell Arteritis
    August 16, 2023VEXAS Syndrome Can Cause Symptoms in the Eyes
    August 15, 2023Inflammatory Pathways Are Activated in VEXAS Hematopoietic Stem Cells
    September 29, 2022Level of UBA1 Production Inside the Cell Contributes to VEXAS Syndrome
    July 6, 2022Understanding the Relationship Between Vascular Inflammation Detected on a PET Scan with Future Risk to Develop Damage Within the Large Arteries

                                                      Core Research Facilities

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

Biodata Mining and Discovery
	Flow Cytometry
	Genomic Technology
	Laboratory Animal Care and Use
	Light Imaging
	Translational Immunology

                                    Staff
                            
            **Peter Grayson, M.D., M.Sc.**Investigatorpeter.grayson@nih.gov
    **Keith A. Sikora, M.D.**Special Volunteerkeith.sikora@nih.gov
    **Lily Dai, M.D.**Senior Research Associatedailz@mail.nih.gov
    **Wendy Goodspeed, R.N.**Contractorgoodspew@mail.nih.gov
    **Chloe Palmer, B.S.**Postbaccalaureate Fellowchloe.palmer@nih.gov
    **Jin Kyun Park, M.D., Ph.D.**Postdoctoral FellowParkj30@nih.gov
    **Kaitlin A. Quinn, M.D.**Staff Cliniciankaitlin.quinn@nih.gov
    **Karyssa Stonick, B.S.**Postbaccalaureate Fellowkaryssa.stonick@nih.gov
    **McKella Sylvester, B.A.**Postbaccalaureate Fellowmckella.sylvester@nih.gov
    **Michelle van der Merwe, B.A., B.S.**Research Nursemichelle.vandermerwe@nih.gov
            
                                                Image & Media Gallery
              
            PET Scan of a Patient with Active Vasculitis
PET Scan of a Patient with Active Vasculitis
        ×
      This movie shows a three-dimensional view of a patient with active giant cell arteritis, a form of vasculitis. It uses a technology called 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET). Vasculitis is a group of diseases involving inflammation in the blood vessels. In the movie, inflammation is seen throughout the aorta and its primary branches (green=mild inflammation, red=severe inflammation).

Photographer: Mark A. Ahlman, M.D. and Peter Grayson, M.D., NIAMS Intramural Research Program
    Grayson Lab Meeting (October 2020)
Grayson Lab Meeting (October 2020)
        ×
      Screenshot of a WebEx call showing a grid with all members of the Grayson Lab
        (top row: Peter Grayson, Hugh Alessi, Keith Sikora; second row: Yiming Luo, Marcela Ferrada, Kaitlin Quinn; third row: Adrianna Jones, Chris Redmond, Emily Rominger; fourth row: Emily Rose, Kristina Wells, Lily Dai).
    Advanced molecular imaging techniques
Advanced molecular imaging techniques
        ×
      Two scientists examining scans on computer monitors
        We work closely with our colleagues in radiology and nuclear medicine to profile vascular inflammation using advanced molecular imaging techniques.
    Giant cell arteritis and Tocilizumab
Giant cell arteritis and Tocilizumab
        ×
      Two body scans showing imflammation
        Images from a patient in our cohort with giant cell arteritis with active vascular inflammation (Panel A) that was ameliorated with tocilizumab (Panel B). (Banerjee et al.)
    Magnetic resonance angiography (MRA)
Magnetic resonance angiography (MRA)
        ×
      MRA scan of patient's upper body
        Magnetic resonance angiography (MRA) of a patients in our research study with Takayasu’s arteritis and severe damage of the aortic arch.
    3D Reconstruction Magnetic Resonance Angiography
3D Reconstruction Magnetic Resonance Angiography
        ×
      Full Body
        3D Reconstruction Magnetic Resonance Angiography detailing the aorta and branch arteries in a healthy volunteer in our research study.
    FDG-PET and MR angiography
FDG-PET and MR angiography
        ×
      Newman et al.
        FDG-PET and MR angiography can be used as complementary modalities to assess vascular inflammation and damage in large-vessel vasculitis (Quinn et al.)
    Temporal artery biopsy
Temporal artery biopsy
        ×
      Section through artery
        Temporal artery biopsy demonstrating active vasculitis in a patient diagnosed within giant cell arteritis.
    Vascular inflammation
Vascular inflammation
        ×
      Progression
        Use of FDG-PET to monitor vascular inflammation over time in a patient enrolled in our research study.
    PET Scan on MRI Platform
PET Scan on MRI Platform
        ×
      Imaging modalities and sequences are employed to assess vascular inflammation in patients with vasculitis.
        Our group has capability to perform FDG-PET scans coupled to an MRI platform. Since the MRI platform minimizes radiation exposure, we are able to perform vascular imaging studies in pediatric populations.
            
                        
                                    Clinical Trials
              
              
            RecruitingStudies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic VasculitisClinicalTrials.gov Identifier: NCT02257866Vasculitis 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.
            
                                    Scientific Publications
              Selected Recent Publications
                  
      Clonal haematopoiesis across the age spectrum of vasculitis patients with Takayasu's arteritis, ANCA-associated vasculitis and giant cell arteritis.

    Gutierrez-Rodrigues F, Wells KV, Jones AI, Hironaka D, Rankin C, Gadina M, Sikora KA, Alemu L, Calado RT, Quinn KA, Patel B, Young NS, Grayson PC
        

                    Ann Rheum Dis.
        
                    2024 Mar 12;
        
                    83(4).
        
                    doi: 10.1136/ard-2023-224933
                            PMID: 38049983
              Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study.

    Luo Y, Ferrada MA, Sikora KA, Rankin C, Alessi HD, Kastner DL, Deng Z, Zhang M, Merkel PA, Kraus VB, Allen AS, Grayson PC
        

                    Ann Rheum Dis.
        
                    2024 Jan 11;
        
                    83(2).
        
                    doi: 10.1136/ard-2023-224732
                            PMID: 37918895
              Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.

    Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
        

                    JAMA.
        
                    2023 Jan 24;
        
                    329(4).
        
                    doi: 10.1001/jama.2022.24836
                            PMID: 36692560
              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
                
                                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 PCJ Nucl Med.2022 Feb;63(2).doi: 10.2967/jnumed.121.262326PMID: 34088771VEXAS syndrome.Grayson PC, Patel BA, Young NSBlood.2021 Jul 1;137(26).doi: 10.1182/blood.2021011455PMID: 33971000Somatic 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 PCN Engl J Med.2020 Dec 31;383(27).doi: 10.1056/NEJMoa2026834PMID: 33108101Defining 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 PCArthritis Rheumatol.2020 Aug;72(8).doi: 10.1002/art.41270PMID: 32249511Deficiency 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 PCBlood.2019 Jul 25;134(4).doi: 10.1182/blood.2018892752PMID: 31015188 
                            See all Publications on PubMed
            
                                    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.
Read More
    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.
Read More



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        Last Updated: April 2024
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