ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers

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ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers. / Morris, Hannah; Morgan, Matthew; Turner, Alice; Smith, Stuart; Ekeowa, UI; Herrmann, K; Holle, JU; Guillevin, L; Lomas, DA; Perez, J; Pusey, CD; Salama, AD; Stockley, Robert; Wieczorek, S; McKnight, AJ; Maxwell, AP; Miranda, E; Williams, Julie; Savage, Caroline; Harper, Lorraine.

In: Annals of the Rheumatic Diseases, Vol. 70, No. 10, 01.10.2011, p. 1851-1856.

Research output: Contribution to journalArticle

Harvard

Morris, H, Morgan, M, Turner, A, Smith, S, Ekeowa, UI, Herrmann, K, Holle, JU, Guillevin, L, Lomas, DA, Perez, J, Pusey, CD, Salama, AD, Stockley, R, Wieczorek, S, McKnight, AJ, Maxwell, AP, Miranda, E, Williams, J, Savage, C & Harper, L 2011, 'ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers', Annals of the Rheumatic Diseases, vol. 70, no. 10, pp. 1851-1856. https://doi.org/10.1136/ard.2011.153569

APA

Morris, H., Morgan, M., Turner, A., Smith, S., Ekeowa, UI., Herrmann, K., Holle, JU., Guillevin, L., Lomas, DA., Perez, J., Pusey, CD., Salama, AD., Stockley, R., Wieczorek, S., McKnight, AJ., Maxwell, AP., Miranda, E., Williams, J., Savage, C., & Harper, L. (2011). ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers. Annals of the Rheumatic Diseases, 70(10), 1851-1856. https://doi.org/10.1136/ard.2011.153569

Vancouver

Author

Morris, Hannah ; Morgan, Matthew ; Turner, Alice ; Smith, Stuart ; Ekeowa, UI ; Herrmann, K ; Holle, JU ; Guillevin, L ; Lomas, DA ; Perez, J ; Pusey, CD ; Salama, AD ; Stockley, Robert ; Wieczorek, S ; McKnight, AJ ; Maxwell, AP ; Miranda, E ; Williams, Julie ; Savage, Caroline ; Harper, Lorraine. / ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers. In: Annals of the Rheumatic Diseases. 2011 ; Vol. 70, No. 10. pp. 1851-1856.

Bibtex

@article{adc0b75d5c784a1590e0461bdf5bfe6e,
title = "ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers",
abstract = "Background Small studies have linked alpha 1 antitrypsin (alpha 1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Objective To test the validity and the mechanism of this association between alpha 1AT and AAV. Methods The distribution of alpha 1AT deficiency alleles Z and S was compared between 856 White Europeans with AAV and 1505 geographic and ethnically matched healthy controls. Genotyping was performed by allelic discrimination assay. Results were compared between cases and controls using chi(2) tests. The serum and renal biopsies for alpha 1AT polymers were compared using the polymer-specific 2C1 antibody. The role of alpha 1AT polymers in promoting inflammation was investigated by examining their ability to prime neutrophils for ANCA activation as assessed by CD62L shedding, superoxide production and myeloperoxidase degranulation. Results The Z but not the S allele was over-represented in the patients compared with controls (HR=2.25, 95% CI 1.60 to 3.19). Higher concentrations of polymers of alpha 1AT were detected in serum from patients carrying the Z allele than in those not carrying the Z allele (median (IQR) 1.40 (0.91-3.32) mg/dl vs 0.17 (0.06-0.28) mg/dl, p",
author = "Hannah Morris and Matthew Morgan and Alice Turner and Stuart Smith and UI Ekeowa and K Herrmann and JU Holle and L Guillevin and DA Lomas and J Perez and CD Pusey and AD Salama and Robert Stockley and S Wieczorek and AJ McKnight and AP Maxwell and E Miranda and Julie Williams and Caroline Savage and Lorraine Harper",
year = "2011",
month = oct,
day = "1",
doi = "10.1136/ard.2011.153569",
language = "English",
volume = "70",
pages = "1851--1856",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - ANCA-associated vasculitis is linked to carriage of the Z allele of alpha(1) antitrypsin and its polymers

AU - Morris, Hannah

AU - Morgan, Matthew

AU - Turner, Alice

AU - Smith, Stuart

AU - Ekeowa, UI

AU - Herrmann, K

AU - Holle, JU

AU - Guillevin, L

AU - Lomas, DA

AU - Perez, J

AU - Pusey, CD

AU - Salama, AD

AU - Stockley, Robert

AU - Wieczorek, S

AU - McKnight, AJ

AU - Maxwell, AP

AU - Miranda, E

AU - Williams, Julie

AU - Savage, Caroline

AU - Harper, Lorraine

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Background Small studies have linked alpha 1 antitrypsin (alpha 1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Objective To test the validity and the mechanism of this association between alpha 1AT and AAV. Methods The distribution of alpha 1AT deficiency alleles Z and S was compared between 856 White Europeans with AAV and 1505 geographic and ethnically matched healthy controls. Genotyping was performed by allelic discrimination assay. Results were compared between cases and controls using chi(2) tests. The serum and renal biopsies for alpha 1AT polymers were compared using the polymer-specific 2C1 antibody. The role of alpha 1AT polymers in promoting inflammation was investigated by examining their ability to prime neutrophils for ANCA activation as assessed by CD62L shedding, superoxide production and myeloperoxidase degranulation. Results The Z but not the S allele was over-represented in the patients compared with controls (HR=2.25, 95% CI 1.60 to 3.19). Higher concentrations of polymers of alpha 1AT were detected in serum from patients carrying the Z allele than in those not carrying the Z allele (median (IQR) 1.40 (0.91-3.32) mg/dl vs 0.17 (0.06-0.28) mg/dl, p

AB - Background Small studies have linked alpha 1 antitrypsin (alpha 1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Objective To test the validity and the mechanism of this association between alpha 1AT and AAV. Methods The distribution of alpha 1AT deficiency alleles Z and S was compared between 856 White Europeans with AAV and 1505 geographic and ethnically matched healthy controls. Genotyping was performed by allelic discrimination assay. Results were compared between cases and controls using chi(2) tests. The serum and renal biopsies for alpha 1AT polymers were compared using the polymer-specific 2C1 antibody. The role of alpha 1AT polymers in promoting inflammation was investigated by examining their ability to prime neutrophils for ANCA activation as assessed by CD62L shedding, superoxide production and myeloperoxidase degranulation. Results The Z but not the S allele was over-represented in the patients compared with controls (HR=2.25, 95% CI 1.60 to 3.19). Higher concentrations of polymers of alpha 1AT were detected in serum from patients carrying the Z allele than in those not carrying the Z allele (median (IQR) 1.40 (0.91-3.32) mg/dl vs 0.17 (0.06-0.28) mg/dl, p

U2 - 10.1136/ard.2011.153569

DO - 10.1136/ard.2011.153569

M3 - Article

C2 - 21821620

VL - 70

SP - 1851

EP - 1856

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 10

ER -