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

被引:0
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作者
Akbaba, Tayfun Hilmi [1 ,2 ,3 ]
Toor, Kirandeep K. [1 ,4 ]
Mann, Simranpreet K. [1 ,5 ]
Gibson, Kristen M. [1 ,6 ]
Alfaro, Gabriel Alejandro [7 ]
Balci-Peynircioglu, Banu [3 ]
Cabral, David A. [1 ,2 ,8 ]
Morishita, Kimberly A. [1 ,2 ,8 ]
Brown, Kelly L. [1 ,2 ,8 ]
机构
[1] BC Childrens Hosp, Res Inst, Vancouver, BC V5Z 4H4, Canada
[2] Univ British Columbia, Dept Pediat, Div Rheumatol, Vancouver, BC V6T 1Z4, Canada
[3] Hacettepe Univ, Fac Med, Dept Med Biol, TR-06800 Ankara, Turkiye
[4] Univ British Columbia, Women & Childrens Hlth Sci, Vancouver, BC V6T 1Z4, Canada
[5] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z4, Canada
[6] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z4, Canada
[7] Meso Scale Diagnost LLC, Rockville, MD 20850 USA
[8] BC Childrens Hosp, Vancouver, BC V6H 3V4, Canada
基金
加拿大健康研究院;
关键词
lysosome-associated membrane protein-2; anti-neutrophil cytoplasmic antibodies; childhood-onset primary vasculitis; autoantibodies; Takayasu's arteritis; polyarteritis nodosa; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; HENOCH-SCHONLEIN PURPURA; CRESCENTIC GLOMERULONEPHRITIS; ANCA; CLASSIFICATION; GRANULOMATOSIS; AUTOANTIBODIES; DISEASE; RELAPSE; LAMP-2;
D O I
10.3390/ijms25073771
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:15
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