Evaluation of ANCA in vasculitis and non-vasculitis diseases

Yıl 2024, Cilt: 17 Sayı: 1, 1 - 8, 01.01.2024

Sedef Zeliha Öner Melek Demir Burhan Özkan Ergun Mete İlknur Kaleli Ahmet Çalışkan Cagri Ergin

https://doi.org/10.31362/patd.1276753

Öz

Purpose: The present study aims to evaluate the existence of anti-neutrophil cytoplasmic antibody (ANCA) in vasculitis and non-vasculitis diseases.
Materials and methods: Over five years, the results of 5107 serum samples submitted to the Medical Microbiology Laboratory for ANCA evaluation were retrospectively analyzed. The existence of ANCA was studied using the preparations containing ethanol-fixed and formalin-fixed granulocyte substratum by indirect immunofluorescence (IIF) testing method; and myeloperoxidase (MPO) and Proteinase-3 (PR-3) antigens in ANCA-positive samples were studied with the ELISA method.
Results: 422 (8.3%) of the samples were considered ANCA-positive. The mean age of ANCA-positive patients was found significantly high from ANCA-negative patients (p=0.0001). ANCA-positivity was 6.7% in men and 9.4% in women. A statistically significant difference was detected between women and men in terms of ANCA positivity (p=0.0001). 62 (19.9%) of the 312 patients diagnosed with vasculitis and 360 (7.5%) of the 4795 patients with non-vasculitis were ANCA-positive. The age of ANCA-associated vasculitis (AAV) patients was statistically high compared to non-AAV patients (p=0.0001). ANCA-positivity was found 16.7% in patients with IgA vasculitis, 18.6% in leukocytoclastic vasculitis, 56.9% in rheumatoid arthritis, 46.9% in systemic lupus erythematosus, 18.6% in interstitial pulmonary disease, 7.7% multiple sclerosis, 10.2% in chronic renal failure, and 5.1% in cerebrovascular accident.
Conclusion: In vasculitis cases, ANCA positivity rate was higher than in non-vasculitis diseases. In nonvasculitis diseases, the target antigen MPO-ANCA and PR3-ANCA positivity was rare compared to vasculitis cases. Among ANCA-positive patients, the most common non-vasculitis diseases included connective tissue disease, chronic renal failure and interstitial pulmonary disease.

Anahtar Kelimeler

Anti-neutrophil cytoplasmic antibody, MPO-ANCA, PR3-ANCA, vasculitis, connective tissue disease

ANCA'nın vaskülit ve vaskülit dışı hastalıklarda değerlendirilmesi

Öz

Amaç: Bu çalışma, vaskülit ve vaskülit dışı hastalıklarda anti-nötrofil sitoplazmik antikorun (ANCA) varlığını değerlendirmeyi amaçlamaktadır.
Gereç ve yöntem: Beş yılı aşkın bir sürede ANCA değerlendirmesi için Tıbbi Mikrobiyoloji Laboratuvarına gönderilen 5107 serum örneğinin sonuçları retrospektif olarak incelendi. ANCA'nın varlığı, etanolle fikse edilmiş ve formalinle fikse edilmiş granülosit substrat içeren preparatlar kullanılarak indirekt immünofloresan (IIF) test yöntemiyle araştırıldı; ANCA pozitif örneklerde miyeloperoksidaz (MPO) ve Proteinaz-3 (PR-3) antijenleri ELISA yöntemi ile çalışıldı.
Bulgular: Örneklerin 422'si (%8,3) ANCA-pozitif olarak değerlendirildi. ANCA pozitifliği erkeklerde %6,7 ve kadınlarda %9,4 idi. ANCA pozitifliği açısından kadın ve erkekler arasında istatistiksel olarak anlamlı fark saptandı (p=0,0001). ANCA pozitif hastaların ortalama yaşı ANCA negatif hastalardan anlamlı olarak yüksek bulundu (p=0,0001). Vaskülit tanısı alan 312 hastanın 62'si (%19,9) ve vasküliti olmayan 4795 hastanın 360'ı (%7,5) ANCA pozitifti. AAV hastalarının yaşı, AAV olmayan hastalara göre istatistiksel olarak yüksekti (p=0,0001). ANCA pozitifliği IgA vaskülitlerinde %16,7, lökositoklastik vaskülitlerde %18,6, romatoid artritte %56,9, sistemik lupus eritematozusta %46,9, interstisyel akciğer hastalığında %18,6, multipl sklerozda %7,7, kronik böbrek yetmezliğinde %10,2 ve serebrovasküler olayda %5,1olarak bulunmuştur.
Sonuç: Vaskülit olgularında ANCA pozitiflik oranı, vaskülit dışı hastalıklara göre daha yüksekti. Vaskülit dışı hastalıklarda hedef antijen MPO-ANCA ve PR3-ANCA pozitifliği vaskülit vakalarına göre nadirdi. ANCA-pozitif hastalar arasında en yaygın vaskülit dışı hastalıklar bağ dokusu hastalığı, kronik böbrek yetmezliği ve interstisyel akciğer hastalığıydı.

Anahtar Kelimeler

Anti-nötrofil sitoplazmik antikor, MPO-ANCA, PR3-ANCA, vaskülit, bağ dokusu hastalığı

Kaynakça

• 1. Suwanchote S, Rachayon M, Rodsaward P, et al. Anti-neutrophil cytoplasmic antibodies and their clinical significance. Clin Rheumatol 2018;37:875-884. https://doi.org/10.1007/s10067-018-4062-x
• 2. Al Hussain T, Hussein MH, Conca W, Al Mana H, Akhtar M. Pathophysiology of ANCA-associated vasculitis. Adv Anat Pathol 2017;24:226-234. https://doi.org/10.1097/PAP.0000000000000154
• 3. Moiseev S, Tervaert JWC, Arimura Y, et al. 2020 international consensus on ANCA testing beyond systemic vasculitis. Autoimmun Rev 2020;19:102618. https://doi.org/10.1016/j.atrev.2020.102618
• 4. Van Beers JJBC, Vanderlocht J, Roozendaal C, Damoiseaux J. Detection of anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence. Methods Mol Biol 2019;1901:47-62. https://doi.org/10.1007/978-1-4939-8949-2_4
• 5. Sais G, Vidaller A, Jucgla A, Servitje O, Condom E, Peyrí J. Prognostic factors in leukocytoclastic vasculitis: a clinicopathologic study of 160 patients. Arch Dermatol 1998;134:309-315. https://doi.org/10.1001/archderm.134.3.309
• 6. Kim JY, Choi H, Kim MK, Lee SB, Park YB, Lee SW. Clinical significance of ANCA positivity in patients with IgA vasculitis: a retrospective monocentric study. Rheumatol Int 2019;39:1927-1936. https://doi.org/10.1007/s00296-019-04397-3
• 7. Fteiha B, Bnaya A, Abu Sneineh M, Nesher G, Breuer GS. Clinical implications of ANCA positivity in a hospital setting: a tertiary center experience. Intern Emerg Med 2021;16:429-436. https://doi.org/10.1007/s11739-020-02518-6
• 8. Houben E, Bax WA, van Dam B, et al. Diagnosing ANCA-associated vasculitis in ANCA positive patients: a retrospective analysis on the role of clinical symptoms and the ANCA titre. Medicine 2016;95:e5096. https://doi.org/10.1097/MD.0000000000005096
• 9. Cornec D, Cornec Le Gall E, Fervenza FC, Specks U. ANCA-associated vasculitis-clinical utility of using ANCA specificity to classify patients. Nat Rev Rheumatol 2016;12:570-579. https://doi.org/10.1038/nrrheum.2016.123
• 10. Fraticelli P, Benfaremo D, Gabrielli A. Diagnosis and management of leukocytoclastic vasculitis. Intern Emerg Med 2021;16:831-841. https://doi.org/10.1007/s11739-021-02688-x
• 11. Sobral S, Ramassur K, Apsley E, Isenberg D. Do anti-neutrophil cytoplasmic antibodies play a role in systemic lupus erythematosus (SLE) patients? Analysis of the University College Hospital SLE cohort. Lupus 2018;27:343-344. https://doi.org/10.1177/0961203317724218
• 12. Santacruz Sandoval E, Aragón CC, Nieto Aristizábal I, et al. Frequency of anti-neutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus. Revista Colombiana de Reumatología 2022;29:107-112. https://doi.org/10.1016/j.rcreu.2021.01.002
• 13. Bahmer T, Romagnoli M, Girelli F, Claussen M, Rabe KF. The use of auto-antibody testing in the evaluation of interstitial lung disease (ILD)--a practical approach for the pulmonologist. Respir Med 2016;113:80-92. https://doi.org/10.1016/j.rmed.2016.01.019
• 14. Dal Bianco A, Wenhoda F, Rommer PS, et al. Do elevated autoantibodies in patients with multiple sclerosis matter?. Acta Neurol Scand 2019;139:238-246. https://doi.org/10.1111/ane.13054
• 15. Long Y, Zheng Y, Chen M, et al. Antineutrophil cytoplasmic antibodies in patients with idiopathic inflammatory-demyelinating diseases. Neuroimmunomodulation 2014;21:297-303. https://doi.org/10.1159/000357681
• 16. Fukazawa T, Hamada T, Kikuchi S, Sasaki H, Tashiro K, Maguchi S. Antineutrophil cytoplasmic antibodies and the optic-spinal form of multiple sclerosis in Japan. J Neurol Neurosurg Psychiatry 1996;61:203-204. https://doi.org/10.1136/jnnp.61.2.203-a
• 17. Choi H, Park YB, Song J, Lee SW. Unclassifiable repeated antineutrophil cytoplasmic antibody (ANCA) positivity in diseases other than ANCA-associated vasculitis. Z Rheumatol 2022;81:705-711. https://doi.org/10.1007/s00393-021-00998-1
• 18. Chehroudi C, Booth RA, Milman N. Diagnostic outcome and indications for testing in patients with positive ANCA at a Canadian tertiary care centre. Rheumatol Int 2018;38:641-647. https://doi.org/10.1007/s00296-017-3905-0