Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels
department or school: Medicine, Faculty of
department or school: Science, Faculty of
department or school: Non UBC
department or school: Medical Genetics, Department of
department or school: Microbiology and Immunology, Department of
department or school: Pediatrics, Department of
department or school: Obstetrics and Gynaecology, Department of
data provider: DSpace
identifier citation: International Journal of Molecular Sciences 25 (7): 3771 (2024)
contributor: Children's Hospital (Vancouver, B.C.). Research Institute
contributor: Children's Hospital (Vancouver, B.C.)
creator: Akbaba, Tayfun Hilmi
creator: Toor, Kirandeep K.
creator: Mann, Simranpreet K.
creator: Gibson, Kristen M.
creator: Alfaro, Gabriel Alejandro
creator: Balci-Peynircioglu, Banu
creator: Cabral, David A.
creator: Morishita, Kimberly
creator: Brown, Kelly L.
issued: 2024-04-26T14:59:28Z
issued: 2024-03-28
description: Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/88008
note: Citation: Akbaba, T.H.; Toor, K.K.;Mann, S.K.; Gibson, K.M.; Alfaro,G.A.; Balci-Peynircioglu, B.; Cabral,D.A.; Morishita, K.A.; Brown, K.L., onbehalf of the PedVas Investigator’sNetwork. Anti-LAMP-2 AntibodySeropositivity in Children withPrimary Systemic Vasculitis AffectingMedium- and Large-Sized Vessels. Int.J. Mol. Sci. 2024, 25, 3771. https://doi.org/10.3390/ijms25073771Academic Editor: Hajime KonoReceived: 20 February 2024Revised: 18 March 2024Accepted: 21 March 2024Published: 28 March 2024Copyright: © 2024 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). International Journal of Molecular SciencesArticleAnti-LAMP-2 Antibody Seropositivity in Children with PrimarySystemic Vasculitis Affecting Medium- and Large-Sized VesselsTayfun Hilmi Akbaba 1,2,3,† , Kirandeep K. Toor 1,4,†, Simranpreet K. Mann 1,5 , Kristen M. Gibson 1,6,Gabriel Alejandro Alfaro 7, Banu Balci-Peynircioglu 3, David A. Cabral 1,2,8, Kimberly A. Morishita 1,2,8and Kelly L. Brown 1,2,8,*,‡ on behalf of the PedVas Investigator’s Network1 BC Children’s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada2 Division of Rheumatology, Department of Pediatrics, University of British Columbia,Vancouver, BC V6T 1Z4, Canada3 Department of Medical Biology, Faculty of Medicine, Hacettepe University, 06800 Ankara, Turkey4 Women+ and Children’s Health Sciences, University of British Columbia, Vancouver, BC V6T 1Z4, Canada5 Department of Microbiology and Immunology, University of British Columbia,Vancouver, BC V6T 1Z4, Canada6 Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada7 Meso Scale Diagnostics, LLC, Rockville, MD 20850, USA8 BC Children’s Hospital, Vancouver, BC V6H 3V4, Canada* Correspondence: kbrown@bcchr.ca; Tel.: +1-604-875-2000 (ext. 7984)† These authors contributed equally …
has type: Article
is shown at: 10.14288/1.0441958
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/ijms25073771
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: lysosome-associated membrane protein-2
subject: anti-neutrophil cytoplasmic antibodies
subject: childhood-onset primary vasculitis
subject: autoantibodies
subject: Takayasu’s arteritis
subject: polyarteritis nodosa
type: Text
identifier URI: http://hdl.handle.net/2429/88008