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Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis

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Abstract

Objectives

We investigated whether low serum C3 level can cross-sectionally estimate severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in immunosuppressive drug-naïve patients at diagnosis.

Methods

We retrospectively reviewed the medical records of 139 patients with AAV, who were first classified as AAV at Severance Hospital. We obtained clinical and laboratory data including serum complement 3 (C3) level and calculated Birmingham vasculitis activity score (BVAS) at diagnosis. We stratified AAV patients into three groups according to the tertile of BVAS and defined the lower limit of the highest tertile as the cutoff for severe AAV (BVAS at diagnosis ≥ 16) at diagnosis. Low serum C3 level was defined as C3 < 90 mg/dL. The odds ratio (OR) was assessed using the multivariable logistic regression.

Results

The mean age at diagnosis was 56.3 years and 41 patients were men (29.5%). The mean initial BVAS was 12.8. The mean serum C3 and C4 levels were 110.6 and 26.8 mg/dL. Thirty-one patients (22.3%) exhibited low serum C3 level at diagnosis. In the multivariable analysis, serum C3 level at diagnosis < 90 mg/dL (OR 2.963) exhibited the significant association with severe AAV at diagnosis. Patients with low serum C3 level exhibited a significantly high relative risk (RR) for severe AAV at diagnosis compared to those without (RR 3.600). Patients with low serum C3 level at diagnosis exhibited poor renal prognosis than those without.

Conclusion

Low serum C3 level can estimate severe AAV and predict poor renal outcome in immunosuppressive drug-naïve patients at diagnosis.

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References

  1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1–11. https://doi.org/10.1002/art.37715

    Article  Google Scholar 

  2. Watts R, Lane S, Hanslik T, et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007;66(2):222–7. https://doi.org/10.1136/ard.2006.054593.

    Article  PubMed  Google Scholar 

  3. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum. 1990;33(8):1101–7.

    Article  CAS  PubMed  Google Scholar 

  4. Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33(8):1094–100.

    Article  CAS  PubMed  Google Scholar 

  5. Charles Jennette J, Xiao H, Hu P. Complement in ANCA-associated vasculitis. Semin Nephrol. 2013;33(6):557–64. https://doi.org/10.1016/j.semnephrol.2013.08.006.

    Article  CAS  PubMed  Google Scholar 

  6. Kallenberg CG, Stegeman CA, Abdulahad WH, Heeringa P. Pathogenesis of ANCA-associated vasculitis: new possibilities for intervention. Am J Kidney Dis. 2013;62(6):1176–87. https://doi.org/10.1053/j.ajkd.2013.05.009.

    Article  CAS  PubMed  Google Scholar 

  7. Jennette JC, Falk RJ, Hu P, Xiao H. Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Annu Rev Pathol. 2013;24:8:139–60. https://doi.org/10.1146/annurev-pathol-011811-132453.

    Article  CAS  Google Scholar 

  8. Villacorta J, Diaz-Crespo F, Acevedo M, et al. Circulating C3 levels predict renal and global outcome in patients with renal vasculitis. Clin Rheumatol. 2016;35(11):2733–40. https://doi.org/10.1007/s10067-016-3384-9.

    Article  PubMed  Google Scholar 

  9. Manenti L, Vaglio A, Gnappi E, et al. Association of serum C3 concentration and histologic signs of thrombotic microangiopathy with outcomes among patients with ANCA-associated renal vasculitis. Clin J Am Soc Nephrol. 2015;10(12):2143–51. https://doi.org/10.2215/CJN.00120115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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. 2018;31(2):257–62. https://doi.org/10.1007/s40620-017-0445-3.

    Article  CAS  PubMed  Google Scholar 

  11. Augusto JF, Langs V, Demiselle J, et al. Low serum complement C3 levels at diagnosis of renal ANCA-associated vasculitis is associated with poor prognosis. PLoS One. 2016;11(7):e0158871. https://doi.org/10.1371/journal.pone.0158871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen SF, Wang FM, Li ZY, Yu F, Zhao MH, Chen M. Plasma complement factor H is associated with disease activity of patients with ANCA-associated vasculitis. Arthritis Res Ther. 2015;17:129. https://doi.org/10.1186/s13075-015-0656-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gou SJ, Yuan J, Chen M, Yu F, Zhao MH. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2013;83(1):129–37. https://doi.org/10.1038/ki.2012.313.

    Article  CAS  PubMed  Google Scholar 

  14. Mukhtyar C, Lee R, Brown D, et al. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis. 2009;68(12):1827–32. https://doi.org/10.1136/ard.2008.101279.

    Article  CAS  PubMed  Google Scholar 

  15. Stone JH, Hoffman GS, Merkel PA, et al. A disease-specific activity index for Wegener’s granulomatosis: modification of the Birmingham vasculitis activity score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum. 2001;44(4):912–20. https://doi.org/10.1002/1529-0131(200104)44:4%3C912::AID-ANR148%3E3.0.CO;2-5.

    Article  CAS  PubMed  Google Scholar 

  16. Guillevin L, Pagnoux C, Seror R, et al. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011;90(1):19–27. https://doi.org/10.1097/MD.0b013e318205a4c6.

    Article  Google Scholar 

  17. Csernok E, Moosig F. Current and emerging techniques for ANCA detection in vasculitis. Nat Rev Rheumatol. 2014;10(8):494–501. https://doi.org/10.1038/nrrheum.2014.78.

    Article  CAS  PubMed  Google Scholar 

  18. Kim SJ, Koo HM, Lim BJ, et al. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy. PLoS One. 2012;7(7):e40495. https://doi.org/10.1371/journal.pone.0040495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hebert LA, Cosio FG, Neff JC. Diagnostic significance of hypocomplementemia. Kidney Int. 1991;39(5):811–21.

    Article  CAS  PubMed  Google Scholar 

  20. Lappegård KT, Garred P, Jonasson L, et al. A vital role for complement in heart disease. Mol Immunol. 2014;61(2):126–34. https://doi.org/10.1016/j.molimm.2014.06.036.

    Article  CAS  PubMed  Google Scholar 

  21. Yasojima K, Schwab C, McGeer EG, McGeer PL. Human heart generates complement proteins that are upregulated and activated after myocardial infarction. Circ Res. 1998;83(8):860–9.

    Article  CAS  PubMed  Google Scholar 

  22. Kallenberg CG, Heeringa P. Complement is crucial in the pathogenesis of ANCA-associated vasculitis. Kidney Int. 2013;83(1):16–8. https://doi.org/10.1038/ki.2012.371.

    Article  CAS  PubMed  Google Scholar 

  23. Gou SJ, Yuan J, Wang C, Zhao MH, Chen M. Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN. Clin J Am Soc Nephrol. 2013;8(11):1884–91. https://doi.org/10.2215/CJN.02790313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03029050) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI14C1324).

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Authors and Affiliations

Authors

Contributions

All authors contributed to the study concept, design, acquisition, and interpretation of data. HC, YHK, and SWL performed the statistical analysis. HC, YHK, YBP, and SWL drafted and revised manuscript. All authors have read and approved the manuscript for publication.

Corresponding author

Correspondence to Sang-Won Lee.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was approved by the institutional Review Board of Severance Hospital (4-2017-0673).

Informed consent

The patient’s written informed consent was waived by the approving IRB, as this was a retrospective study.

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Choi, H., Kim, Y., Jung, S.M. et al. Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis. Clin Exp Nephrol 23, 223–230 (2019). https://doi.org/10.1007/s10157-018-1634-7

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  • DOI: https://doi.org/10.1007/s10157-018-1634-7

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