Ewa Berglin1, Aladdin J Mohammad2, Johanna Dahlqvist3, Linda Johansson4, Catharina Eriksson5, Johanna Sjöwall6, Solbritt Rantapää-Dahlqvist7. 1. Department of Public Health and Medicine/Rheumatology, Umeå University, Umeå, Sweden. Electronic address: Ewa.Berglin@regionvasterbotten.se. 2. Department of Clinical Sciences/Rheumatology, Lund University, Lund, Sweden; Department of Medicine, University of Cambridge, Cambridge, United Kingdom. Electronic address: aladdin.mohammad@med.lu.se. 3. Department of Medical Biochemistry and Microbiology, and Medical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: johanna.dahlqvist@imbim.uu.se. 4. Department of Public Health and Medicine/Rheumatology, Umeå University, Umeå, Sweden. Electronic address: Linda.e.Johansson@umu.se. 5. Department of Clinical Microbiology, Division of Infection and Immunology, Umeå University, Umeå, Sweden. Electronic address: catharina.eriksson@regionvasterbotten.se. 6. Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases Linköping University Hospital, Linköping, Sweden. Electronic address: johanna.sjowall@liu.se. 7. Department of Public Health and Medicine/Rheumatology, Umeå University, Umeå, Sweden. Electronic address: solbritt.rantapaa.dahlqvist@umu.se.
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 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.
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.
Authors: Anders Esberg; Linda Johansson; Ewa Berglin; Aladdin J Mohammad; Andreas P Jonsson; Johanna Dahlqvist; Bernd Stegmayr; Ingegerd Johansson; Solbritt Rantapää-Dahlqvist Journal: Microorganisms Date: 2022-08-04
Authors: Enrico Brunetta; Giacomo Ramponi; Marco Folci; Maria De Santis; Emanuela Morenghi; Elena Vanni; Elena Bredi; Raffaello Furlan; Claudio Angelini; Carlo Selmi Journal: Front Immunol Date: 2021-09-10 Impact factor: 7.561