Skip to main content
Top
Published in: Immunologic Research 6/2020

Open Access 01-12-2020 | Hypersensitivity Pneumonitis | Original Article

Utility of serological biomarker’ panels for diagnostic accuracy of interstitial lung diseases

Authors: Laura Bergantini, Miriana d’Alessandro, Lucia Vietri, Giuseppe Domenico Rana, Paolo Cameli, Silvia Acerra, Piersante Sestini, Elena Bargagli

Published in: Immunologic Research | Issue 6/2020

Login to get access

Abstract

Interstitial lung diseases (ILD) are a heterogeneous group of illnesses of known and unknown aetiology. Differential diagnosis among the three disorders is often challenging. Specific biomarkers with good sensitivity and specificity are therefore needed to predict clinical outcome and guide clinical decisions. The aim of this study was to investigate inflammatory/fibrotic biomarkers, to determine whether single mediators or panels of mediators could be useful to stratify patients into three distinct domains: sarcoidosis, idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (cHP). A total of 163 ILD patients monitored at Siena Referral Centre for Sarcoidosis and other Interstitial Lung Diseases were enrolled in the study. Clinical data, pulmonary function tests and biochemical analytes were retrospectively collected. SAA levels were detected by ELISA kit and Krebs von den Lungen 6 (KL-6) were measured by CLEIA method, for sarcoidosis, cHP and IPF patients. Multiple comparison analysis showed significant differences in C reactive protein (CRP), white blood cell count (WBC) and creatinine levels between the three groups. In the logistic regression model, KL-6, CRP and WBC showed areas under curves (AUC) 0.86, for sarcoidosis diagnosis. The logistic regression model KL-6 and SAA showed the best performance with an AUC 0.81 for discriminating IPF than cHP and sarcoidosis. For differential diagnosis of IPF and cHP, KL-6 and SAA were considered in the logistic regression model, showed an AUC 0.79. The combination of serum biomarkers proposed here offers insights into the pathobiology of ILDs. These panels of bioindicators will improve diagnostic accuracy and will be useful in the clinical management of ILDs.
Literature
1.
go back to reference Bargagli E, Cameli P, Carleo A, Refini RM, Bergantini L, D'alessandro M, Vietri L, Perillo F, Volterrani L, Rottoli P, Bini L, Landi C. The effect of cigarette smoking on bronchoalveolar lavage protein profiles from patients with different interstitial lung diseases. Panminerva Med. 2020;62(2):109–115. https://doi.org/10.23736/S0031-0808.19.03754-6. Bargagli E, Cameli P, Carleo A, Refini RM, Bergantini L, D'alessandro M, Vietri L, Perillo F, Volterrani L, Rottoli P, Bini L, Landi C. The effect of cigarette smoking on bronchoalveolar lavage protein profiles from patients with different interstitial lung diseases. Panminerva Med. 2020;62(2):109–115. https://​doi.​org/​10.​23736/​S0031-0808.​19.​03754-6.
2.
go back to reference Cameli P, Carleo A, Bergantini L, Landi C, Prasse A, Bargagli E. Oxidant/antioxidant disequilibrium in idiopathic pulmonary fibrosis pathogenesis. Inflammation. 2020;43(1):1–7.PubMedCrossRef Cameli P, Carleo A, Bergantini L, Landi C, Prasse A, Bargagli E. Oxidant/antioxidant disequilibrium in idiopathic pulmonary fibrosis pathogenesis. Inflammation. 2020;43(1):1–7.PubMedCrossRef
3.
go back to reference Ryerson CJ, Collard HR. Update on the diagnosis and classification of ILD. Curr Opin Pulm Med. 2013;19(5):453–9.PubMedCrossRef Ryerson CJ, Collard HR. Update on the diagnosis and classification of ILD. Curr Opin Pulm Med. 2013;19(5):453–9.PubMedCrossRef
4.
go back to reference Bergantini L, Bianchi F, Cameli P, Mazzei MA, Fui A, Sestini P, et al. Prognostic biomarkers of Sarcoidosis: a comparative study of serum Chitotriosidase, ACE, lysozyme, and KL-6. Dis Markers. 2019;2019:8565423.PubMedPubMedCentralCrossRef Bergantini L, Bianchi F, Cameli P, Mazzei MA, Fui A, Sestini P, et al. Prognostic biomarkers of Sarcoidosis: a comparative study of serum Chitotriosidase, ACE, lysozyme, and KL-6. Dis Markers. 2019;2019:8565423.PubMedPubMedCentralCrossRef
5.
go back to reference Cameli P, Gonnelli S, Bargagli E, d’Alessandro M, Bergantini L, Favetta V, et al. The role of urinary calcium and Chitotriosidase in a cohort of chronic Sarcoidosis patients. Respir Int Rev Thorac Dis. 2020;99(3):207–12. Cameli P, Gonnelli S, Bargagli E, d’Alessandro M, Bergantini L, Favetta V, et al. The role of urinary calcium and Chitotriosidase in a cohort of chronic Sarcoidosis patients. Respir Int Rev Thorac Dis. 2020;99(3):207–12.
6.
go back to reference Enyedi A, Csongrádi A, Altorjay IT, Beke GL, Váradi C, Enyedi EE, et al. Combined application of angiotensin converting enzyme and chitotriosidase analysis improves the laboratory diagnosis of sarcoidosis. Clin Chim Acta. 2020;500:155–62.PubMedCrossRef Enyedi A, Csongrádi A, Altorjay IT, Beke GL, Váradi C, Enyedi EE, et al. Combined application of angiotensin converting enzyme and chitotriosidase analysis improves the laboratory diagnosis of sarcoidosis. Clin Chim Acta. 2020;500:155–62.PubMedCrossRef
7.
8.
go back to reference d’Alessandro M, Bergantini L, Perrone A, Cameli P, Cameli M, Prasse A, et al. Serial investigation of angiotensin-converting enzyme in sarcoidosis patients treated with angiotensin-converting enzyme inhibitor. Eur J Intern Med. 2020;78:58–62.PubMedCrossRef d’Alessandro M, Bergantini L, Perrone A, Cameli P, Cameli M, Prasse A, et al. Serial investigation of angiotensin-converting enzyme in sarcoidosis patients treated with angiotensin-converting enzyme inhibitor. Eur J Intern Med. 2020;78:58–62.PubMedCrossRef
9.
go back to reference Lanzarone N, Gentili F, Alonzi V, Bergantini L, d'Alessandro M, Rottoli P, Refini RM, Pieroni M, Vietri L, Bianchi F, Mazzei MA, Volterrani L, Perrone A, Cameli P, Bargagli E, Sestini P. Bronchoalveolar lavage and serum KL-6 concentrations in chronic hypersensitivity pneumonitis: correlations with radiological and immunological features. Intern Emerg Med. 2020;15(7):1247–1254. https://doi.org/10.1007/s11739-020-02281-8. Lanzarone N, Gentili F, Alonzi V, Bergantini L, d'Alessandro M, Rottoli P, Refini RM, Pieroni M, Vietri L, Bianchi F, Mazzei MA, Volterrani L, Perrone A, Cameli P, Bargagli E, Sestini P. Bronchoalveolar lavage and serum KL-6 concentrations in chronic hypersensitivity pneumonitis: correlations with radiological and immunological features. Intern Emerg Med. 2020;15(7):1247–1254. https://​doi.​org/​10.​1007/​s11739-020-02281-8.
10.
go back to reference Cameli P, Bargagli E, Bergantini L, Refini RM, Pieroni M, Sestini P, et al. Evaluation of multiple-flows exhaled nitric oxide in idiopathic and non-idiopathic interstitial lung disease. J Breath Res. 2019;27;13(2):026008.CrossRef Cameli P, Bargagli E, Bergantini L, Refini RM, Pieroni M, Sestini P, et al. Evaluation of multiple-flows exhaled nitric oxide in idiopathic and non-idiopathic interstitial lung disease. J Breath Res. 2019;27;13(2):026008.CrossRef
11.
go back to reference Bargagli E, Di Masi M, Perruzza M, Vietri L, Bergantini L, Torricelli E, et al. The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis. Intern Emerg Med. 2019;14(1):39–43.PubMedCrossRef Bargagli E, Di Masi M, Perruzza M, Vietri L, Bergantini L, Torricelli E, et al. The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis. Intern Emerg Med. 2019;14(1):39–43.PubMedCrossRef
12.
go back to reference Bergantini L, d'Alessandro M, Cameli P, Carleo A, Landi C, Vietri L, Lanzarone N, Pieroni M, Sestini P, Bargagli E. Antithrombin III as predictive indicator of survival in IPF patients treated with Nintedanib: a preliminary study. Intern Med J. 2020. https://doi.org/10.1111/imj.14768. Bergantini L, d'Alessandro M, Cameli P, Carleo A, Landi C, Vietri L, Lanzarone N, Pieroni M, Sestini P, Bargagli E. Antithrombin III as predictive indicator of survival in IPF patients treated with Nintedanib: a preliminary study. Intern Med J. 2020. https://​doi.​org/​10.​1111/​imj.​14768.
13.
go back to reference Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;01;198(5):e44–68.CrossRef Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;01;198(5):e44–68.CrossRef
14.
go back to reference Campo I, Zorzetto M, Bonella F. Facts and promises on lung biomarkers in interstitial lung diseases. Expert Rev Respir Med. 2015;9(4):437–57.PubMedCrossRef Campo I, Zorzetto M, Bonella F. Facts and promises on lung biomarkers in interstitial lung diseases. Expert Rev Respir Med. 2015;9(4):437–57.PubMedCrossRef
15.
go back to reference Bergantini L, Cameli P, d’Alessandro M, Vagaggini C, Refini RM, Landi C, et al. NK and NKT-like cells in granulomatous and fibrotic lung diseases. Clin Exp Med. 2019;19(4):487–94.PubMedCrossRef Bergantini L, Cameli P, d’Alessandro M, Vagaggini C, Refini RM, Landi C, et al. NK and NKT-like cells in granulomatous and fibrotic lung diseases. Clin Exp Med. 2019;19(4):487–94.PubMedCrossRef
16.
go back to reference d’Alessandro M, Carleo A, Cameli P, Bergantini L, Perrone A, Vietri L, et al. BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases. Clin Exp Med [Internet]. 2020 [cited 2020 Apr 7]; Available from; 20:207–16. https://doi.org/10.1007/s10238-020-00608-5. d’Alessandro M, Carleo A, Cameli P, Bergantini L, Perrone A, Vietri L, et al. BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases. Clin Exp Med [Internet]. 2020 [cited 2020 Apr 7]; Available from; 20:207–16. https://​doi.​org/​10.​1007/​s10238-020-00608-5.
17.
go back to reference Bargagli E, Madioni C, Bianchi N, Refini RM, Cappelli R, Rottoli P. Serum analysis of coagulation factors in IPF and NSIP. Inflammation. 2014;37(1):10–6.PubMedCrossRef Bargagli E, Madioni C, Bianchi N, Refini RM, Cappelli R, Rottoli P. Serum analysis of coagulation factors in IPF and NSIP. Inflammation. 2014;37(1):10–6.PubMedCrossRef
18.
go back to reference Wakamatsu K, Nagata N, Kumazoe H, Oda K, Ishimoto H, Yoshimi M, et al. Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis. Respir Investig. 2017;55(1):16–23.PubMedCrossRef Wakamatsu K, Nagata N, Kumazoe H, Oda K, Ishimoto H, Yoshimi M, et al. Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis. Respir Investig. 2017;55(1):16–23.PubMedCrossRef
19.
go back to reference Shigemura M, Konno S, Nasuhara Y, Shijubo N, Shimizu C, Nishimura M. Serum KL-6 concentrations are associated with molecular sizes and efflux behavior of KL-6/MUC1 in healthy subjects. Clin Chim Acta Int J Clin Chem. 2013;424:148–52.CrossRef Shigemura M, Konno S, Nasuhara Y, Shijubo N, Shimizu C, Nishimura M. Serum KL-6 concentrations are associated with molecular sizes and efflux behavior of KL-6/MUC1 in healthy subjects. Clin Chim Acta Int J Clin Chem. 2013;424:148–52.CrossRef
20.
go back to reference d’Alessandro M, Bergantini L, Cameli P, Vietri L, Lanzarone N, Alonzi V, et al. Krebs von den Lungen-6 as a biomarker for disease severity assessment in interstitial lung disease: a comprehensive review. Biomark Med. 2020;14(8):665–74.PubMedCrossRef d’Alessandro M, Bergantini L, Cameli P, Vietri L, Lanzarone N, Alonzi V, et al. Krebs von den Lungen-6 as a biomarker for disease severity assessment in interstitial lung disease: a comprehensive review. Biomark Med. 2020;14(8):665–74.PubMedCrossRef
21.
go back to reference Satoh H, Kurishima K, Ishikawa H, Ohtsuka M. Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med. 2006 Nov;260(5):429–34.PubMedCrossRef Satoh H, Kurishima K, Ishikawa H, Ohtsuka M. Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med. 2006 Nov;260(5):429–34.PubMedCrossRef
22.
go back to reference d’Alessandro M, Bergantini L, Cameli P, Lanzarone N, Mazzei MA, Alonzi V, et al. Serum KL-6 levels in pulmonary Langerhans’ cell Histiocytosis. Eur J Clin Investig. 2020;20:e13242. d’Alessandro M, Bergantini L, Cameli P, Lanzarone N, Mazzei MA, Alonzi V, et al. Serum KL-6 levels in pulmonary Langerhans’ cell Histiocytosis. Eur J Clin Investig. 2020;20:e13242.
23.
go back to reference Vietri L, Fui A, Bergantini L, d’Alessandro M, Cameli P, Sestini P, et al. Serum amyloid a: a potential biomarker of lung disorders. Respir Investig. 2020 Jan;58(1):21–7.PubMedCrossRef Vietri L, Fui A, Bergantini L, d’Alessandro M, Cameli P, Sestini P, et al. Serum amyloid a: a potential biomarker of lung disorders. Respir Investig. 2020 Jan;58(1):21–7.PubMedCrossRef
24.
go back to reference Ather JL, Dienz O, Boyson JE, Anathy V, Amiel E, Poynter ME. Serum amyloid A3 is required for normal lung development and survival following influenza infection. Sci Rep. 2018;8(1):16571.PubMedPubMedCentralCrossRef Ather JL, Dienz O, Boyson JE, Anathy V, Amiel E, Poynter ME. Serum amyloid A3 is required for normal lung development and survival following influenza infection. Sci Rep. 2018;8(1):16571.PubMedPubMedCentralCrossRef
25.
go back to reference Bargagli E, Magi B, Olivieri C, Bianchi N, Landi C, Rottoli P. Analysis of serum amyloid A in sarcoidosis patients. Respir Med. 2011;105(5):775–80.PubMedCrossRef Bargagli E, Magi B, Olivieri C, Bianchi N, Landi C, Rottoli P. Analysis of serum amyloid A in sarcoidosis patients. Respir Med. 2011;105(5):775–80.PubMedCrossRef
26.
go back to reference Hisata S, Kimura Y, Shibata N, Ono S, Kobayashi T, Chiba S, Ohta H, Nukiwa T, Ebina M. A Normal Range of KL-6/MUC1 Independent of Elevated SP-D Indicates a Better Prognosis in the Patients with Honeycombing on High-Resolution Computed Tomography. Pulm Med. 2011;2011:806014. https://doi.org/10.1155/2011/806014. Hisata S, Kimura Y, Shibata N, Ono S, Kobayashi T, Chiba S, Ohta H, Nukiwa T, Ebina M. A Normal Range of KL-6/MUC1 Independent of Elevated SP-D Indicates a Better Prognosis in the Patients with Honeycombing on High-Resolution Computed Tomography. Pulm Med. 2011;2011:806014. https://​doi.​org/​10.​1155/​2011/​806014.
27.
go back to reference Salisbury ML, Myers JL, Belloli EA, Kazerooni EA, Martinez FJ, Flaherty KR. Diagnosis and treatment of fibrotic hypersensitivity pneumonia. Where we stand and where we need to go. Am J Respir Crit Care Med. 2017;15;196(6):690–9.CrossRef Salisbury ML, Myers JL, Belloli EA, Kazerooni EA, Martinez FJ, Flaherty KR. Diagnosis and treatment of fibrotic hypersensitivity pneumonia. Where we stand and where we need to go. Am J Respir Crit Care Med. 2017;15;196(6):690–9.CrossRef
28.
go back to reference Lopes MC, Amadeu TP, Ribeiro-Alves M, da Costa CH, Rodrigues LS, Bessa EJC, et al. Identification of active Sarcoidosis using Chitotriosidase and angiotensin-converting enzyme. Lung. 2019;197(3):295–302.PubMedCrossRef Lopes MC, Amadeu TP, Ribeiro-Alves M, da Costa CH, Rodrigues LS, Bessa EJC, et al. Identification of active Sarcoidosis using Chitotriosidase and angiotensin-converting enzyme. Lung. 2019;197(3):295–302.PubMedCrossRef
29.
go back to reference Ramos-Casals M, Retamozo S, Sisó-Almirall A, Pérez-Alvarez R, Pallarés L, Brito-Zerón P. Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis. Expert Rev Clin Immunol. 2019;15(4):391–405.PubMedCrossRef Ramos-Casals M, Retamozo S, Sisó-Almirall A, Pérez-Alvarez R, Pallarés L, Brito-Zerón P. Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis. Expert Rev Clin Immunol. 2019;15(4):391–405.PubMedCrossRef
30.
go back to reference Landi C, Bargagli E, Carleo A, Refini RM, Bennett D, Bianchi L, et al. Bronchoalveolar lavage proteomic analysis in pulmonary fibrosis associated with systemic sclerosis: S100A6 and 14-3-3ε as potential biomarkers. Rheumatol Oxf Engl. 2019;58(1):165–78. Landi C, Bargagli E, Carleo A, Refini RM, Bennett D, Bianchi L, et al. Bronchoalveolar lavage proteomic analysis in pulmonary fibrosis associated with systemic sclerosis: S100A6 and 14-3-3ε as potential biomarkers. Rheumatol Oxf Engl. 2019;58(1):165–78.
31.
go back to reference Bergantini L, Bargagli E, Cameli P, Cekorja B, Lanzarone N, Pianigiani L, et al. Serial KL-6 analysis in patients with idiopathic pulmonary fibrosis treated with nintedanib. Respir Investig. 2019;57(3):290–1. Bergantini L, Bargagli E, Cameli P, Cekorja B, Lanzarone N, Pianigiani L, et al. Serial KL-6 analysis in patients with idiopathic pulmonary fibrosis treated with nintedanib. Respir Investig. 2019;57(3):290–1.
32.
go back to reference Davies BH, Williams JD, Smith MD, Jones-Williams W, Jones K. Peripheral blood lymphocytes in sarcoidosis. Pathol Res Pract. 1982;175(1):97–109.PubMedCrossRef Davies BH, Williams JD, Smith MD, Jones-Williams W, Jones K. Peripheral blood lymphocytes in sarcoidosis. Pathol Res Pract. 1982;175(1):97–109.PubMedCrossRef
34.
go back to reference Uysal P, Durmus S, Sozer V, Gelisgen R, Seyhan EC, Erdenen F, et al. YKL-40, soluble IL-2 receptor, angiotensin converting enzyme and C-reactive protein: comparison of markers of sarcoidosis activity. Biomolecules. 2018;28:8(3). Uysal P, Durmus S, Sozer V, Gelisgen R, Seyhan EC, Erdenen F, et al. YKL-40, soluble IL-2 receptor, angiotensin converting enzyme and C-reactive protein: comparison of markers of sarcoidosis activity. Biomolecules. 2018;28:8(3).
35.
go back to reference Mukhopadhyay S, Gal AA. Granulomatous lung disease: an approach to the differential diagnosis. Arch Pathol Lab Med. 2010;134(5):667–90.PubMed Mukhopadhyay S, Gal AA. Granulomatous lung disease: an approach to the differential diagnosis. Arch Pathol Lab Med. 2010;134(5):667–90.PubMed
36.
go back to reference Jiang Y, Luo Q, Han Q, Huang J, Ou Y, Chen M, et al. Sequential changes of serum KL-6 predict the progression of interstitial lung disease. J Thorac Dis. 2018;10(8):4705–14.PubMedPubMedCentralCrossRef Jiang Y, Luo Q, Han Q, Huang J, Ou Y, Chen M, et al. Sequential changes of serum KL-6 predict the progression of interstitial lung disease. J Thorac Dis. 2018;10(8):4705–14.PubMedPubMedCentralCrossRef
37.
go back to reference White ES, Xia M, Murray S, Dyal R, Flaherty CM, Flaherty KR, et al. Plasma surfactant protein-D, matrix metalloproteinase-7, and osteopontin index distinguishes idiopathic pulmonary fibrosis from other idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2016;15;194(10):1242–51.CrossRef White ES, Xia M, Murray S, Dyal R, Flaherty CM, Flaherty KR, et al. Plasma surfactant protein-D, matrix metalloproteinase-7, and osteopontin index distinguishes idiopathic pulmonary fibrosis from other idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2016;15;194(10):1242–51.CrossRef
38.
go back to reference Mahendran S, Sethi T. Treatments in idiopathic pulmonary fibrosis: time for a more targeted approach? QJM Mon J Assoc Physicians. 2012;105(10):929–34.CrossRef Mahendran S, Sethi T. Treatments in idiopathic pulmonary fibrosis: time for a more targeted approach? QJM Mon J Assoc Physicians. 2012;105(10):929–34.CrossRef
39.
go back to reference C L, A C, L V, L B, d’Alessandro M null PC, et al. Common molecular pathways targeted by nintedanib in cancer and IPF: a bioinformatic study. Pulm Pharmacol Ther. 2020;64:101941.PubMedCrossRef C L, A C, L V, L B, d’Alessandro M null PC, et al. Common molecular pathways targeted by nintedanib in cancer and IPF: a bioinformatic study. Pulm Pharmacol Ther. 2020;64:101941.PubMedCrossRef
40.
go back to reference Huangfu X-Q, Wang L-G, Le Z-D, Tao B. Utility of serum amyloid A as a potential prognostic biomarker of acute primary basal ganglia hemorrhage. Clin Chim Acta Int J Clin Chem. 2020;505:43–8.CrossRef Huangfu X-Q, Wang L-G, Le Z-D, Tao B. Utility of serum amyloid A as a potential prognostic biomarker of acute primary basal ganglia hemorrhage. Clin Chim Acta Int J Clin Chem. 2020;505:43–8.CrossRef
41.
go back to reference Vietri L, Bennett D, Cameli P, Bergantini L, Cillis G, Sestini P, et al. Serum amyloid A in patients with idiopathic pulmonary fibrosis. Respir Investig. 2019;57(5):430–4.PubMedCrossRef Vietri L, Bennett D, Cameli P, Bergantini L, Cillis G, Sestini P, et al. Serum amyloid A in patients with idiopathic pulmonary fibrosis. Respir Investig. 2019;57(5):430–4.PubMedCrossRef
Metadata
Title
Utility of serological biomarker’ panels for diagnostic accuracy of interstitial lung diseases
Authors
Laura Bergantini
Miriana d’Alessandro
Lucia Vietri
Giuseppe Domenico Rana
Paolo Cameli
Silvia Acerra
Piersante Sestini
Elena Bargagli
Publication date
01-12-2020
Publisher
Springer US
Published in
Immunologic Research / Issue 6/2020
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-020-09158-0

Other articles of this Issue 6/2020

Immunologic Research 6/2020 Go to the issue