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Predicting bacterial infection risk in patients with ANCA-associated vasculitis in southwest China: development of a new nomogram

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Abstract

Objectives

The aim of this study was to develop and assess a risk nomogram of bacterial infection in patients with ANCA-associated vasculitis (AAV) in southwest China.

Method

We established a prediction model based on a training dataset of 249 AAV patients. The least absolute shrinkage and selection operator (Lasso) was used to screen feature variables. Multivariate logistic regression analysis was used to build a prediction model for feature variables. Nomogram was used to predict the risk of bacterial infection in AAV patients. Receiver operating characteristic (ROC) curve was used to evaluate and verify the prediction accuracy of the model. Calibration and clinical useful range was assessed using calibration curve and decision curve analysis, respectively.

Results

Bactericidal permeability enhancement protein of ANCAs (BPI-ANCAs), procalcitonin (PCT), and white blood cell (WBC) were the characteristic variables in this study. Nomogram showed that positive BPI-ANCAs and PCT had higher positive predictive value for bacterial infection in AAV patients. The area under curve (AUC) of the model was 0.703 (95% confidence interval: 0.640–0.766). In the validation model, the AUC was 0.745 (95% confidence interval: 0.617–0.872). Decision curve analysis showed that the nonadherence nomogram was clinically useful within the threshold probability range of 0.31–0.85.

Conclusions

Nomogram combined with BPI-ANCAs and PCT has the guiding significance for predicting bacterial infection risk in AAV. As an ANCA-specific autoantibody, BPI-ANCAs is helpful for clinicians to understand the role of specific autoantibodies in the pathogenesis of AAV.

Key Points

• BPI-ANCAs, PCT, and WBC could predict bacterial infection in AAV patients.

• Nomogram showed that positive BPI-ANCAs had a high positive predictive value for bacterial infection in AAV patients.

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References

  1. Deng X, Gao J, Zhao F (2022) Identification of differentially expressed genes and pathways in kidney of ANCA-associated vasculitis by integrated bioinformatics analysis. Ren Fail 44(1):204–216. https://doi.org/10.1080/0886022X.2022.2030755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thery-Casari C, Euvrard R, Mainbourg S, Durupt S, Reynaud Q, Durieu I, Belot A, Lobbes H, Cabrera N, Lega JC (2020) Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: a meta-analysis. Autoimmun Rev 19(5):102505. https://doi.org/10.1016/j.autrev.2020.102505

    Article  CAS  PubMed  Google Scholar 

  3. Hirano K, Tokui T, Inagaki M, Fujii T, Maze Y, Toyoshima H (2017) Aggregatibacter aphrophilus infective endocarditis confirmed by broad-range PCR diagnosis: a case report. Int J Surg Case Rep 31:150–153. https://doi.org/10.1016/j.ijscr.2017.01.041

    Article  PubMed  PubMed Central  Google Scholar 

  4. Garcia-Vives E, Segarra-Medrano A, Martinez-Valle F, Agraz I, Solans-Laque R (2020) Prevalence and risk factors for major infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis: influence on the disease outcome. J Rheumatol 47(3):407–414. https://doi.org/10.3899/jrheum.190065

    Article  PubMed  Google Scholar 

  5. Mosakowska M, Kania DB, Szamotulska K, Rymarz A, Niemczyk S (2021) Assessment of the correlation of commonly used laboratory tests with clinical activity, renal involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies. BMC Nephrol 22(1):290. https://doi.org/10.1186/s12882-021-02495-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Willeke P, Kumpers P, Schluter B, Limani A, Becker H, Schotte H (2015) Platelet counts as a biomarker in ANCA-associated vasculitis. Scand J Rheumatol 44(4):302–308. https://doi.org/10.3109/03009742.2015.1006247

    Article  CAS  PubMed  Google Scholar 

  7. Herrmann K, Schinke S, Csernok E, Moosig F, Holle JU (2015) Diagnostic value of procalcitonin in ANCA-associated vasculitis (AAV) to differentiate between disease activity, infection and drug hypersensitivity. Open Rheumatol J 9:71–76. https://doi.org/10.2174/1874312901409010071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sunderkotter CH, Zelger B, Chen KR, Requena L, Piette W, Carlson JA, Dutz J, Lamprecht P, Mahr A, Aberer E, Werth VP, Wetter DA, Kawana S, Luqmani R, Frances C, Jorizzo J, Watts JR, Metze D, Caproni M, Alpsoy E, Callen JP, Fiorentino D, Merkel PA, Falk RJ, Jennette JC (2018) Nomenclature of cutaneous vasculitis: dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheumatol 70(2):171–184. https://doi.org/10.1002/art.40375

    Article  PubMed  Google Scholar 

  9. Walsh M, Merkel PA, Peh CA, Szpirt WM, Puechal X, Fujimoto S, Hawley CM, Khalidi N, Flossmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suarez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW, Investigators P (2020) Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med 382(7):622–631. https://doi.org/10.1056/NEJMoa1803537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. El Sharouni MA, Ahmed T, Varey AHR, Elias SG, Witkamp AJ, Sigurdsson V, Suijkerbuijk KPM, van Diest PJ, Scolyer RA, van Gils CH, Thompson JF, Blokx WAM, Lo SN (2021) Development and validation of nomograms to predict local, regional, and distant recurrence in patients with thin (T1) melanomas. J Clin Oncol 39(11):1243–1252. https://doi.org/10.1200/JCO.20.02446

    Article  CAS  PubMed  Google Scholar 

  11. Gafita A, Calais J, Grogan TR, Hadaschik B, Wang H, Weber M, Sandhu S, Kratochwil C, Esfandiari R, Tauber R, Zeldin A, Rathke H, Armstrong WR, Robertson A, Thin P, D’Alessandria C, Rettig MB, Delpassand ES, Haberkorn U, Elashoff D, Herrmann K, Czernin J, Hofman MS, Fendler WP, Eiber M (2021) Nomograms to predict outcomes after (177)Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Lancet Oncol 22(8):1115–1125. https://doi.org/10.1016/S1470-2045(21)00274-6

    Article  CAS  PubMed  Google Scholar 

  12. Yang L, Xia L, Wang Y, He S, Chen H, Liang S, Peng P, Hong S, Chen Y (2017) Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma. BMC Cancer 17(1):628. https://doi.org/10.1186/s12885-017-3630-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rathmann J, Jayne D, Segelmark M, Jonsson G, Mohammad AJ (2021) Incidence and predictors of severe infections in ANCA-associated vasculitis: a population-based cohort study. Rheumatology (Oxford) 60(6):2745–2754. https://doi.org/10.1093/rheumatology/keaa699

    Article  Google Scholar 

  14. Sarica SH, Dhaun N, Sznajd J, Harvie J, McLaren J, McGeoch L, Kumar V, Amft N, Erwig L, Marks A, Black C, Basu N (2020) Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study. Rheumatology (Oxford) 59(10):3014–3022. https://doi.org/10.1093/rheumatology/keaa070

    Article  Google Scholar 

  15. Houben E, Bax WA, van Dam B, Slieker WAT, Verhave G, Frerichs FCP, van Eijk IC, Boersma WG, de Kuyper GTM, Penne EL (2016) Diagnosing ANCA-associated vasculitis in ANCA positive patients: a retrospective analysis on the role of clinical symptoms and the ANCA titre. Medicine (Baltimore) 95(40):e5096. https://doi.org/10.1097/MD.0000000000005096

    Article  CAS  Google Scholar 

  16. Dunogue B, Pagnoux C, Guillevin L (2011) Churg-strauss syndrome: clinical symptoms, complementary investigations, prognosis and outcome, and treatment. Semin Respir Crit Care Med 32(3):298–309. https://doi.org/10.1055/s-0031-1279826

    Article  PubMed  Google Scholar 

  17. Ledo N, Petho AG (2021) Gastrointestinal symptoms as first remarkable signs of ANCA-associated granulomatosis with polyangiitis: a case report and reviews. BMC Gastroenterol 21(1):158. https://doi.org/10.1186/s12876-021-01730-8

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhang N, Sun J, Ji C, Zhou Y, Bao X, Yuan C (2020) Clinical significance and influencing factors of fibrinogen in ANCA-associated vasculitis: a single-center retrospective study from Southwest China. Medicine (Baltimore) 99(39):e22424. https://doi.org/10.1097/MD.0000000000022424

    Article  CAS  Google Scholar 

  19. Schultz H, Weiss JP (2007) The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease. Clin Chim Acta 384(1–2):12–23. https://doi.org/10.1016/j.cca.2007.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Aichele D, Schnare M, Saake M, Rollinghoff M, Gessner A (2006) Expression and antimicrobial function of bactericidal permeability-increasing protein in cystic fibrosis patients. Infect Immun 74(8):4708–4714. https://doi.org/10.1128/IAI.02066-05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hovold G, Lindberg U, Ljungberg JK, Shannon O, Pahlman LI (2020) BPI-ANCA is expressed in the airways of cystic fibrosis patients and correlates to platelet numbers and Pseudomonas aeruginosa colonization. Respir Med 170:105994. https://doi.org/10.1016/j.rmed.2020.105994

    Article  PubMed  Google Scholar 

  22. Skopelja S, Hamilton BJ, Jones JD, Yang ML, Mamula M, Ashare A, Gifford AH, Rigby WF (2016) The role for neutrophil extracellular traps in cystic fibrosis autoimmunity. JCI Insight 1(17):e88912. https://doi.org/10.1172/jci.insight.88912

    Article  PubMed  PubMed Central  Google Scholar 

  23. Schultz H (2007) From infection to autoimmunity: a new model for induction of ANCA against the bactericidal/permeability increasing protein (BPI). Autoimmun Rev 6(4):223–227. https://doi.org/10.1016/j.autrev.2006.08.005

    Article  CAS  PubMed  Google Scholar 

  24. Schultz H, Schinke S, Mosler K, Herlyn K, Schuster A, Gross WL (2004) BPI-ANCA of pediatric cystic fibrosis patients can impair BPI-mediated killing of E. coli DH5alpha in vitro. Pediatr Pulmonol 37(2):158–164 https://doi.org/10.1002/ppul.10416

  25. Schultz H, Csernok E, Schuster A, Schmitz TS, Ernst M, Gross WL (2000) Anti-neutrophil cytoplasmic antibodies directed against the bactericidal/permeability-increasing protein (BPI) in pediatric cystic fibrosis patients do not recognize N-terminal regions important for the anti-microbial and lipopolysaccharide-binding activity of BPI. Pediatr Allergy Immunol 11(2):64–70. https://doi.org/10.1034/j.1399-3038.2000.00069.x

    Article  CAS  PubMed  Google Scholar 

  26. Aebi C, Theiler F, Aebischer CC, Schoeni MH (2000) Autoantibodies directed against bactericidal/permeability-increasing protein in patients with cystic fibrosis: association with microbial respiratory tract colonization. Pediatr Infect Dis J 19(3):207–212. https://doi.org/10.1097/00006454-200003000-00006

    Article  CAS  PubMed  Google Scholar 

  27. Komatsuda A, Omokawa A, Fujiwara T, Sato R, Togashi M, Okuyama S, Sawada KI, Wakui H (2012) Serum procalcitonin levels in patients with myeloperoxidase-antineutrophil cytoplasmic antibodies-associated glomerulonephritis. Am J Med Sci 343(2):136–140. https://doi.org/10.1097/MAJ.0b013e31822846db

    Article  PubMed  Google Scholar 

  28. Papp M, Sipeki N, Vitalis Z, Tornai T, Altorjay I, Tornai I, Udvardy M, Fechner K, Jacobsen S, Teegen B, Sumegi A, Veres G, Lakatos PL, Kappelmayer J, Antal-Szalmas P (2013) High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis. J Hepatol 59(3):457–466. https://doi.org/10.1016/j.jhep.2013.04.018

    Article  CAS  PubMed  Google Scholar 

  29. Zycinska K, Wardyn KA, Zielonka TM, Tyszko P, Straburzynski M (2008) Procalcitonin as an indicator of systemic response to infection in active pulmonary Wegener’s granulomacytosis. J Physiol Pharmacol 59(Suppl 6):839–844

    PubMed  Google Scholar 

  30. Brunkhorst R, Eberhardt OK, Haubitz M, Brunkhorst FM (2000) Procalcitonin for discrimination between activity of systemic autoimmune disease and systemic bacterial infection. Intensive Care Med 26(Suppl 2):S199-201. https://doi.org/10.1007/BF02900738

    Article  PubMed  Google Scholar 

  31. Delevaux I, Andre M, Colombier M, Albuisson E, Meylheuc F, Begue RJ, Piette JC, Aumaitre O (2003) Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? Ann Rheum Dis 62(4):337–340. https://doi.org/10.1136/ard.62.4.337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Clementi A, Brocca A, Virzi GM, de Cal M, Giavarina D, Carta M, Mucino-Bermejo MJ, Hinna Danesi T, Salvador L, Ronco C (2017) Procalcitonin and interleukin-6 levels: are they useful biomarkers in cardiac surgery patients? Blood Purif 43(4):290–297. https://doi.org/10.1159/000454672

    Article  CAS  PubMed  Google Scholar 

  33. Zheng W, Liang X, Shui L, Ye B, Lou G, Liu Y, Zheng M (2018) Serum procalcitonin correlates with renal function in hepatitis b virus-related acute-on-chronic liver failure. Cell Physiol Biochem 50(5):1794–1803. https://doi.org/10.1159/000494820

    Article  CAS  PubMed  Google Scholar 

  34. Quan X, Feng C, He J, Li F, Liao M, Wen J, Wang X, Hou Y, Yang H, Wei L (2021) Serum procalcitonin correlates with renal function and immune components in early-stage renal transplant recipients. Transplant Proc 53(3):927–932. https://doi.org/10.1016/j.transproceed.2021.01.032

    Article  CAS  PubMed  Google Scholar 

  35. Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R (1997) Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum 40(7):1250–1256. https://doi.org/10.1002/1529-0131

    Article  CAS  PubMed  Google Scholar 

  36. Xu HG, Tian M, Pan SY (2022) Clinical utility of procalcitonin and its association with pathogenic microorganisms. Crit Rev Clin Lab Sci 59(2):93–111. https://doi.org/10.1080/10408363.2021.1988047

    Article  CAS  PubMed  Google Scholar 

  37. Cheng Y, Wang TY, Yuan HL, Li W, Shen JP, He ZX, Chen J, Gao JY, Wang FK, Gu J (2021) Nocardia infection in nephrotic syndrome patients: three case studies and a systematic literature review. Front Cell Infect Microbiol 11:789754. https://doi.org/10.3389/fcimb.2021.789754

    Article  PubMed  Google Scholar 

  38. Hu T, Wang M, Chen W, Zhao J, Xiong J (2020) The clinical characteristic and outcome of skin and soft tissue infection in immunosuppressive patients with nephrotic syndrome. Clin Exp Nephrol 24(9):779–788. https://doi.org/10.1007/s10157-020-01893-w

    Article  CAS  PubMed  Google Scholar 

  39. Shi XD, Li WY, Shao X, Qu LM, Jiang ZY (2020) Infective endocarditis mimicking ANCA-associated vasculitis: does it require immunosuppressive therapy?: a case report and literature review. Medicine (Baltimore) 99(29):e21358. https://doi.org/10.1097/MD.0000000000021358

    Article  Google Scholar 

  40. Varnier GC, Sebire N, Christov G, Eleftheriou D, Brogan PA (2016) Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male. Clin Rheumatol 35(9):2369–2372. https://doi.org/10.1007/s10067-016-3337-3

    Article  PubMed  Google Scholar 

  41. Penafiel-Sam J, Alarcon-Guevara S, Chang-Cabanillas S, Perez-Medina W, Mendo-Urbina F, Ordaya-Espinoza E (2017) Infective endocarditis due to Bartonella bacilliformis associated with systemic vasculitis: a case report. Rev Soc Bras Med Trop 50(5):706–708. https://doi.org/10.1590/0037-8682-0042-2017

    Article  PubMed  Google Scholar 

  42. Jennette JC, Falk RJ (2014) Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol 10(8):463–473. https://doi.org/10.1038/nrrheum.2014.103

    Article  CAS  PubMed  Google Scholar 

  43. Fukuda M, Motokawa M, Usami T, Oikawa T, Morozumi K, Yoshida A, Kimura G (2006) PR3-ANCA-positive crescentic necrotizing glomerulonephritis accompanied by isolated pulmonic valve infective endocarditis, with reference to previous reports of renal pathology. Clin Nephrol 66(3):202–209. https://doi.org/10.5414/cnp66202

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Sichuan Medical Association (grant number: 2019HR35) and Chengdu University of Traditional Chinese Medicine Research Foundation (grant number: YYZX2019026).

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Authors and Affiliations

  1. Department of Clinical Laboratory, Peoples Hospital of Deyang City, No 173, the First Section of North Taishan Road, Deyang, 618000, China

    Naidan Zhang, Jiaxiang Sun, Chaixia Ji & Chenliang Yuan

  2. Department of Rheumatology, Peoples Hospital of Deyang City, Deyang, 618000, China

    Xiao Bao

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  1. Naidan Zhang
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Correspondence to Chenliang Yuan.

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This study got permission from the Ethics Committee of Peoples Hospital of Deyang City and was based on the principles of the 1964 Declaration of Helsinki and its later amendment.

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Zhang, N., Sun, J., Ji, C. et al. Predicting bacterial infection risk in patients with ANCA-associated vasculitis in southwest China: development of a new nomogram. Clin Rheumatol 41, 3451–3460 (2022). https://doi.org/10.1007/s10067-022-06314-9

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  • DOI: https://doi.org/10.1007/s10067-022-06314-9

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