A SINGLE CENTRE EXPERIENCE OF LOW C3/C4 LEVELS AND OTHER LABORATORY ASPECTS IN TURKISH CHILDREN WITH IMMUNOGLOBULIN A VASCULITIS

Abstract

Objective: Immunoglobulin A vasculitis (IgAV) is the most prevalent systemic vasculitis in childhood. This intricate immune-mediated vasculitis affects the small blood vessels in several organ systems. Complements 3 and 4 (C3 and C4) are constituents of the complement system; serum C3/ C4 measurements play a Material and Methods: A total of 124 children—60 IgAV patients and 64 healthy controls—were assessed in this study. The C3 and C4 levels were quantified using a turbidimetric immunoassays method with manufacturer details. The extractable nuclear antigen antibody (ENA) panels were evaluated using the ELISA method. The results were evaluated statistically. Results: The white blood cell count, neutrophil count, and neutrophil/ lymphocyte ratio were higher in the patient group compared to the control group (p=0.015, p=0.013 and p=0.039, respectively). CRP, ESR, and random urine protein/creatinine ratio (RUPCR) increased in patients than controls (p<0.001, p=0.002 and p<0.001 respectively). There was no difference in the lupus anticoagulant activity and low C3/C4 levels between the groups (p˃0.05). Conclusion: IgAV, an IgA-mediated systemic small vessel vasculitis, affects many organs. As a result, it is crucial to evaluate the laboratory results in the follow-up of the patient and the possible complications.

Keywords

• Immunoglobulin A vasculitis
• C3
• C4
• immunoassay

İMMÜNOGLOBULİN A VASKÜLİTLİ TÜRK ÇOCUKLARINDA DÜŞÜK C3/ C4 DÜZEYLERİ VE DİĞER LABORATUVAR ÖZELLİKLERİYLE İLGİLİ TEK MERKEZ DENEYİMİ

Abstract

Amaç: Eskiden Henoch-Schönlein purpurası olarak adlandırılan immünog lobulin A vasküliti (IgAV), çocukluk çağında en sık görülen sistemik vaskülit türüdür. Kompleman 3 ve 4 (C3 ve C4) kompleman sisteminin bileşenleri dir ve bazı bağışıklık hastalıklarıyla ilişkili oldukları bulunmuştur. Bu neden le bu çalışmada IgAV’li çocuklarda düşük C3/C4 düzeylerinin yanı sıra diğer laboratuvar bulgularını değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bu çalışmada 60 IgAV hastası ve 64 sağlıklı kontrol olmak üzere toplam 124 çocuk değerlendirildi. C3 ve C4 düzeyleri, üretici ayrıntılarıyla birlikte türbidimetrik immünoanaliz yöntemi kullanılarak ölçüldü. Ekstrakte edilebilir nükleer antijen antikor (ENA) panelleri, enzime bağlı immünosorbent analizleri (ELISA) kullanılarak değerlendirildi. Sonuçlar istatistiksel olarak değerlendirildi. Bulgular: Hasta grubunda lökosit sayısı, nötrofil sayısı ve nötrofil/lenfosit oranı kontrol grubuna göre daha yüksek bulundu (sırasıyla p=0,015, p=0,013 ve p=0,039). Ayrıca hastalarda kontrollere göre CRP, ESR ve rastgele idrar protein/kreatinin oranı (RUPCR) artmış bulundu (sırasıyla p<0,001, p=0,002 ve p<0,001). Düşük C3/C4 seviyeleri ve lupus antikoagülan aktivitesi açısından gruplar arasında anlamlı fark bulunamadı (p˃0,05). Sonuç: IgA aracılı sistemik küçük damar vasküliti olan IgAV, öncelikle böbrekleri, eklemleri, gastrointestinal sistemi ve cildi etkilemektedir. Sonuç olarak, potansiyel hasta durumlarını izlerken laboratuvar sonuçlarının değerlendirilmesi çok önemlidir.

Keywords

• İmmünoglobulin A vasküliti
• C3
• C4
• immünolojik test

References

1. Watts RA, Hatemi G, Burns JC, Mohammad AJ. Global epidemiology ofvasculitis. Nat Rev Rheumatol 2022;18(1):22-34. google scholar
2. Piram M, Mahr A. Epidemiology of immunoglobulin A vasculitis (Henoch-Schönlein): current state of knowledge. Curr Opin Rheumatol 2013;25(2):171-8. google scholar
3. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, et al. 2012 Revised international chapel hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013;65(1):1-11. google scholar
4. Xu L, Li Y, Wu X. IgA vasculitis update: Epidemiology, pathogenesis, and biomarkers. Front Immunol 2022;13:921864. google scholar
5. Ozen S, Marks SD, Brogan P, Groot N, de Graeff N, Avcin T, et al. European Consensus-based recommendations for diagnosis and treatment of immunoglobulin a vasculitis-the SHARE initiative. Rheumatol (Oxford) 2019;58(9):1607-16. google scholar
6. Varela JC, Tomlinson S. Complement: an overview for the clinician. Hematol Oncol Clin North Am 2015;29(3):409-27. google scholar
7. Kallionpaa H, Elo LL, Laajala E, Mykkanen J, Ricano-Ponce I, Vaarma M, et al. Innate Immune Activity Is Detected Prior to Seroconversion in Children With HLA-Conferred Type 1 Diabetes Susceptibility. Diabetes 2014;63(7):2402-14. google scholar
8. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 2007;40(8):560-6. google scholar

9. Crnogorac M, Horvatic I, Kacinari P, Ljubanovic DG, Galesic K. Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a predictor of patient and renal outcome. J Nephrol 2017;31:257-62. google scholar
10. Oni L, Sampath S. Childhood IgA Vasculitis (Henoch Schonlein Purpura)-Advances and Knowledge Gaps. Front Pediatr 2019;27(7):257. google scholar
11. Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev 2017;16(12):1246-53. google scholar
12. Mayer-Hain S, Gebhardt K, Neufeld M, Ehrchen JM, Molyneux K, Barratt J, et al. Systemic activation of neutrophils by immune complexes is critical to igA vasculitis. J Immunol 2022;209(6):1048-58. google scholar
13. Novak J, Raskova Kafkova L, Suzuki H, Tomana M, Matousovic K, Brown R, et al. IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells. Nephrol Dial Transplant 2011;26(11):3451-7. google scholar
14. Yang YH, Tsai IJ, Chang CJ, Chuang YH, Hsu HY, Chiang BL. The interaction between circulating complement proteins and cutaneous microvascular endothelial cells in the development of childhood Henoch-Schönlein Purpura. PloS One 2015;10(3):e0120411. google scholar
15. Holers VM. Complement and its receptors: new insights into human Disease. Annu Rev Immunol 2014;32:433-59. google scholar
16. Coss SL, Zhou D, Chua GT, Aziz RA, Hoffman RP, Wu YL, et al. The Complement System and Human Autoimmune Diseases. J Autoimmun 2022;137:102979. google scholar
17. Riedl M, Noone DG, Khan MA, Pluthero FG, Kahr WHA, Palaniyar N, et al. Complement activation induces neutrophil adhesion and neutrophil-platelet aggregate formation on vascular endothelial cells. Kidney Int Rep 2017;2(1):66-75. google scholar
18. Medjeral-Thomas NR, Cook HT, Pickering MC. Complement activation in IgA nephropathy. Semin Immunopathol 2021;43(5):679-90. google scholar
19. Lionaki S, Marinaki S, Liapis G, Kalaitzakis E, Fragkioudaki S, Kalogeropoulos P, et al. Hypocomplementemia at diagnosis of pauci-immune glomerulonephritis is associated with advanced histopathological activity index and high probability of treatment resistance. Kidney Int Rep 2021;6(9):2425-35. google scholar
20. Li H, Lin S, Yang S, Chen L, Zheng X. Diagnostic value of serum complement C3 and C4 levels in Chinese patients with systemic lupus erythematosus. Clin Rheumatol 2015;34(3):471-7. google scholar
21. Motoyama O, Iitaka K. Henoch-Schonlein purpura with hypocomplementemia in children. Pediatr Int 2005;47(1):39-42. google scholar
22. Ramsey-Goldman R, Alexander RV, Massarotti EM, et al. Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology-Classified Systemic Lupus Erythematosus. Arthritis Rheumatol 2020;72(1):78-88. google scholar
23. Demircioglu Kılıc B, Akbalık Kara M, Buyukcelik M, Balat A. Pediatric post-streptococcal glomerulonephritis: Clinical and laboratory data. Pediatr Int 2018;60(7):645-50. google scholar
24. Balla Z, Andrâsi N, Polai Z, et al. The characteristics of upper airway edema in hereditary and acquired angioedema with C1-inhibitor deficiency. Clin Transl Allergy 2021;11(10):e12083. google scholar
25. Tringali E, Vetrano D, Tondolo F, et al. Role of serum complement C3 and C4 on kidney outcomes in IgA nephropathy. Sci Rep 2024;14(1):16224. google scholar
26. Zinellu A, Mangoni AA. Serum Complement C3 and C4 and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression. Front Immunol 2021;12:696085. google scholar
27. Calvo-Rı'o V, Loricera J, Mata C, Martı'n L, Ortiz-Sanjuân F, Alvarez L, et al. Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center. Clin Exp Rheumatol 2013;31(1 Suppl 75): S45-51. google scholar
28. Trapani S, Micheli A, Grisolia F, Resti M, Chiappini E, Falcini F, et al. Henoch Schonlein purpura in childhood: epidemiological and clinical analysis of 150 cases over a 5-year period and review of literature. Semin Arthritis Rheum 2005;35(3):143-53. google scholar
29. Breda L, Carbone I, Casciato I, Gentile C, Grasso EA, di Donato G, et al. Epidemiological and clinical aspects of immunoglobulin A vasculitis in childhood: a retrospective cohort study. Ital J Pediatr 2021;47:237. google scholar