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Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis. A case-control study

Berglin, Ewa ; Mohammad, Aladdin J. LU ; Dahlqvist, Johanna ; Johansson, Linda ; Eriksson, Catharina ; Sjöwall, Johanna and Rantapää-Dahlqvist, Solbritt (2021) In Journal of Autoimmunity 117.
Abstract

Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from... (More)

Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities. Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively). Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AAV, GPA, MPA, MPO-ANCA, PR3-ANCA, Predate symptom onset
in
Journal of Autoimmunity
volume
117
article number
102579
publisher
Elsevier
external identifiers
  • pmid:33340843
  • scopus:85097887786
ISSN
0896-8411
DOI
10.1016/j.jaut.2020.102579
language
English
LU publication?
yes
id
b960c680-b45f-4e39-8da1-19692bc3297d
date added to LUP
2021-01-04 13:58:30
date last changed
2024-05-31 05:18:16
@article{b960c680-b45f-4e39-8da1-19692bc3297d,
  abstract     = {{<p>Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples &gt;1 month &lt; 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities. Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p &lt; 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P &lt; 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p &lt; 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p &lt; 0.01 and p &lt; 0.05, respectively). Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.</p>}},
  author       = {{Berglin, Ewa and Mohammad, Aladdin J. and Dahlqvist, Johanna and Johansson, Linda and Eriksson, Catharina and Sjöwall, Johanna and Rantapää-Dahlqvist, Solbritt}},
  issn         = {{0896-8411}},
  keywords     = {{AAV; GPA; MPA; MPO-ANCA; PR3-ANCA; Predate symptom onset}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Autoimmunity}},
  title        = {{Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis. A case-control study}},
  url          = {{http://dx.doi.org/10.1016/j.jaut.2020.102579}},
  doi          = {{10.1016/j.jaut.2020.102579}},
  volume       = {{117}},
  year         = {{2021}},
}