Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

Akbaba, Tayfun Hilmi; Toor, Kirandeep K.; Mann, Simranpreet K.; Gibson, Kristen M.; Alfaro, Gabriel Alejandro; Balci-Peynircioglu, Banu; Cabral, David A.; Morishita, Kimberly A.; Brown, Kelly L.

doi:10.3390/ijms25073771

Open AccessArticle

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

by

Tayfun 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

^1,2,8 and

Kelly L. Brown

^1,2,8,*,‡

on behalf of the PedVas Investigator’s Network

¹

BC Children’s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada

²

Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada

³

Department of Medical Biology, Faculty of Medicine, Hacettepe University, 06800 Ankara, Turkey

⁴

Women+ and Children’s Health Sciences, University of British Columbia, Vancouver, BC V6T 1Z4, Canada

⁵

Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada

⁶

Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada

⁷

Meso Scale Diagnostics, LLC, Rockville, MD 20850, USA

⁸

BC Children’s Hospital, Vancouver, BC V6H 3V4, Canada

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Contributing Members of the PedVas Investigator’s Network are indicated in Acknowledgments.

Int. J. Mol. Sci. 2024, 25(7), 3771; https://doi.org/10.3390/ijms25073771

Submission received: 20 February 2024 / Revised: 18 March 2024 / Accepted: 21 March 2024 / Published: 28 March 2024

(This article belongs to the Section Molecular Biology)

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Abstract

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 for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels.

Keywords: lysosome-associated membrane protein-2; anti-neutrophil cytoplasmic antibodies; childhood-onset primary vasculitis; autoantibodies; Takayasu’s arteritis; polyarteritis nodosa

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MDPI and ACS Style

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., on behalf of the PedVas Investigator’s Network. Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels. Int. J. Mol. Sci. 2024, 25, 3771. https://doi.org/10.3390/ijms25073771

AMA Style

Akbaba TH, Toor KK, Mann SK, Gibson KM, Alfaro GA, Balci-Peynircioglu B, Cabral DA, Morishita KA, Brown KL on behalf of the PedVas Investigator’s Network. Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels. International Journal of Molecular Sciences. 2024; 25(7):3771. https://doi.org/10.3390/ijms25073771

Chicago/Turabian Style

Akbaba, Tayfun Hilmi, Kirandeep K. Toor, Simranpreet K. Mann, Kristen M. Gibson, Gabriel Alejandro Alfaro, Banu Balci-Peynircioglu, David A. Cabral, Kimberly A. Morishita, and Kelly L. Brown on behalf of the PedVas Investigator’s Network. 2024. "Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels" International Journal of Molecular Sciences 25, no. 7: 3771. https://doi.org/10.3390/ijms25073771

APA Style

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., on behalf of the PedVas Investigator’s Network. (2024). Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels. International Journal of Molecular Sciences, 25(7), 3771. https://doi.org/10.3390/ijms25073771

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Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

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