Startseite Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis

  • Otto Van de gaer EMAIL logo , Petra de Haes und Xavier Bossuyt
Veröffentlicht/Copyright: 25. April 2020
Veröffentlichen auch Sie bei De Gruyter Brill
Manuskript einreichen Informationen für Autor*innen
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 58 Heft 10

Abstract

Background

Both enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence (IIF) are available for the diagnosis of autoimmune bullous diseases (AIBD). Many studies have reported on the performance of ELISAs and concluded that ELISAs could replace IIF. This study compares the diagnostic accuracy of ELISA and IIF for the detection of autoantibodies to desmoglein 1 (DSG1), desmoglein 3 (DSG3), bullous pemphigoid antigen 2 (BP180) and bullous pemphigoid antigen 1 (BP230) to support the diagnosis of pemphigus vulgaris (PV), pemphigus foliaceus (PF) and bullous pemphigoid (BP).

Methods

A literature search was performed in the PubMed database. The meta-analysis was performed using summary values and a bivariate random effect model.

Results

The five included studies on PV did not demonstrate significant differences between IIF and DSG3-ELISA (sensitivity 82.3% vs. 81.6%, p = 0.9284; specificity 95.6% vs. 93.9%, p = 0.5318; diagnostic odds ratio [DOR] 101.60 vs. 67.760, p = 0.6206). The three included studies on PF did not demonstrate significant differences between IIF and DSG1-ELISA (sensitivity 80.6% vs. 83.1%, p = 0.8501; specificity 97.5% vs. 93.9%, p = 0.3614; DOR 160.72 vs. 75.615, p = 0.5381). The eight included studies on BP showed that BP230-ELISA differed significantly from both IIF on monkey esophagus (MO) and BP180-ELISA with regard to DOR (11.384 vs. 68.349, p = 0.0008; 11.384 vs. 41.699, p = 0.0125, respectively)

Conclusions

Our meta-analysis shows that ELISA performs as well as IIF for diagnosing PV, PF and BP.

Keywords: autoimmune bullous diseases; ELISA; IIF; pemphigus; pemphigoid

  1. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: Authors state no conflict of interest.

References

1. Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification of pemphigus and bullous pemphigoid. Autoimmun Rev 2014;13:477–81.10.1016/j.autrev.2014.01.011Suche in Google Scholar

2. Flowers FP, Sherertz EF. Immunologic disorders of the skin and mucous membranes. Med Clin North Am 1985;69:657–73.10.1016/S0025-7125(16)31013-6Suche in Google Scholar

3. Spindler V, Waschke J. Pemphigus – a disease of desmosome dysfunction caused by multiple mechanisms. Front Immunol 2018;9:136.10.3389/fimmu.2018.00136Suche in Google Scholar PubMed PubMed Central

4. Eyre RW, Stanley JR. Human autoantibodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristic of pemphigus foliaceus patients. J Exp Med 1987;165:1719–24.10.1084/jem.165.6.1719Suche in Google Scholar PubMed PubMed Central

5. Eyre RW, Stanley JR. Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen. J Clin Invest 1988;81:807–12.10.1172/JCI113387Suche in Google Scholar PubMed PubMed Central

6. Tanaka M, Hashimoto T, Amagai M, Shimizu N, Ikeguchi N, Tsubata T, et al. Characterization of bullous pemphigoid antibodies by use of recombinant bullous pemphigoid antigen proteins. J Invest Dermatol 1991;97:725–8.10.1111/1523-1747.ep12484223Suche in Google Scholar PubMed

7. Anhalt GJ, Labib RS, Voorhees JJ, Beals TF, Diaz LA. Induction of pemphigus in neonatal mice by passive transfer of IgG from patients with the disease. N Engl J Med 1982;306:1189–96.10.1056/NEJM198205203062001Suche in Google Scholar PubMed

8. Hertl M, Jedlickova H, Karpati S, Marinovic B, Uzun S, Yayli S, et al. Pemphigus. S2 guideline for diagnosis and treatment – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatology Venereol 2015;29:405–14.10.1111/jdv.12772Suche in Google Scholar PubMed

9. Feliciani C, Joly P, Jonkman MF, Zambruno G, Zillikens D, Ioannides D, et al. Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology. Br J Dermatol 2015;172:867–77.10.1111/bjd.13717Suche in Google Scholar PubMed

10. Stanley JR, Amagai M. Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome. N Engl J Med 2006;355:1800–10.10.1056/NEJMra061111Suche in Google Scholar PubMed

11. Beutner EH. The diagnosis of pemphigus. Br J Dermatol 1971;84:594–7.10.1111/j.1365-2133.1971.tb02549.xSuche in Google Scholar

12. Mihai S, Sitaru C. Immunopathology and molecular diagnosis of autoimmune bullous diseases. J Cell Mol Med 2007;11:462–81.10.1111/j.1582-4934.2007.00033.xSuche in Google Scholar

13. Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: clinical manifestations. JDDG 2011;9:844–57.10.1111/j.1610-0387.2011.07793.xSuche in Google Scholar

14. Alpsoy E, Akman-Karakas A, Uzun S. Geographic variations in epidemiology of two autoimmune bullous diseases: pemphigus and bullous pemphigoid. Arch Dermatol Res 2015;307:291–8.10.1007/s00403-014-1531-1Suche in Google Scholar

15. Meyer N, Misery L. Geoepidemiologic considerations of auto-immune pemphigus. Autoimmun Rev 2010;9:A379–82.10.1016/j.autrev.2009.10.009Suche in Google Scholar

16. Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell 1991;67:869–77.10.1016/0092-8674(91)90360-BSuche in Google Scholar

17. Culton DA, Qian Y, Li N, Rubenstein D, Aoki V, Filhio GH, et al. Advances in pemphigus and its endemic pemphigus foliaceus (fogo selvagem) phenotype: a paradigm of human autoimmunity. J Autoimmun 2008;31:311–24.10.1016/j.jaut.2008.08.003Suche in Google Scholar PubMed PubMed Central

18. Komai A, Amagai M, Ishii K, Nishikawa T, Chorzelski T, Matsuo I, et al. The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay. Br J Dermatol 2001;144:1177–82.10.1046/j.1365-2133.2001.04227.xSuche in Google Scholar PubMed

19. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris – incidence and mortality in the UK: population based cohort study. Br Med J 2008;337:a180.10.1136/bmj.a180Suche in Google Scholar PubMed PubMed Central

20. Brick KE, Weaver CH, Lohse CM, Pittelkow MR, Lehman JS, Camilleri MJ, et al. Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009. J Am Acad Dermatol 2014;71:92–9.10.1016/j.jaad.2014.02.030Suche in Google Scholar PubMed PubMed Central

21. Probst C, Schlumberger W, Stöcker W, Recke A, Schmidt E, Hashimoto T, et al. Development of ELISA for the specific determination of autoantibodies against envoplakin and periplakin in paraneoplastic pemphigus. Clin Chim Acta 2009;410:13–8.10.1016/j.cca.2009.08.022Suche in Google Scholar

22. Schmidt E, Zillikens D. Pemphigoid diseases. Lancet 2013;381:320–32.10.1016/S0140-6736(12)61140-4Suche in Google Scholar

23. Harman KE. New laboratory techniques for the assessment of acquired immunobullous disorders. Clin Exp Dermatol 2002;27:40–6.10.1046/j.0307-6938.2001.00959.xSuche in Google Scholar

24. Otten JV, Hashimoto T, Hertl M, Payne AS, Sitaru C. Molecular diagnosis in autoimmune skin blistering conditions. Curr Mol Med 2014;14:69–95.10.2174/15665240113136660079Suche in Google Scholar

25. Zillikens D. Diagnosis of autoimmune bullous skin diseases. Clin Lab 2008;54:491–503.Suche in Google Scholar

26. Chhabra S, Minz RW, Saikia B. Immunofluorescence in dermatology. Indian J Dermatol Venereol Leprol 2012;78:677–91.10.4103/0378-6323.102355Suche in Google Scholar

27. Aoki V, Sousa JX, Fukumori LM, Périgo AM, Freitas EL, Oliveira ZN. Direct and indirect immunofluorescence. An Bras Dermatol 2010;85:490–500.10.1590/S0365-05962010000400010Suche in Google Scholar

28. Diercks GF, Pas HH, Jonkman MF. Immunofluorescence of autoimmune bullous diseases. Surg Pathol Clin 2017;10:505–12.10.1016/j.path.2017.01.011Suche in Google Scholar

29. Beutner EH, Chorzelski TP, Jablonska S. Immunofluorescence tests. Clinical significance of sera and skin in bullous diseases. Int J Dermatol 1985;24:405–21.10.1111/j.1365-4362.1985.tb05507.xSuche in Google Scholar

30. Ghanadan A, Saghazadeh A, Daneshpazhooh M, Rezaei N. Direct immunofluorescence for immunobullous and other skin diseases. Expert Rev Clin Immunol 2015;11:589–96.10.1586/1744666X.2015.1025059Suche in Google Scholar

31. Gammon WR, Fine JD, Forbes M, Briggaman RA. Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies. J Am Acad Dermatol 1992;27:79–87.10.1016/0190-9622(92)70161-8Suche in Google Scholar

32. Feibelman C, Stolzner G, Provost TT. Pemphigus vulgaris. Arch Dermatol 1981;117:561.10.1001/archderm.1981.01650090043023Suche in Google Scholar

33. Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides 2015;72:4–15.10.1016/j.peptides.2015.04.012Suche in Google Scholar PubMed

34. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Br Med J 2009;339:b2535.10.1136/bmj.b2535Suche in Google Scholar PubMed PubMed Central

35. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529.10.7326/0003-4819-155-8-201110180-00009Suche in Google Scholar PubMed

36. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 2005;58:982–90.10.1016/j.jclinepi.2005.02.022Suche in Google Scholar PubMed

37. Richardson JT. The analysis of 2×2 contingency tables-yet again. Stat Med 2011;30:890.10.1002/sim.4116Suche in Google Scholar PubMed

38. Yoshida M, Hamada T, Amagai M, Hashimoto K, Uehara R, Yamaguchi K, et al. Enzyme-linked immunosorbent assay using bacterial recombinant proteins of human BP230 as a diagnostic tool for bullous pemphigoid. J Dermatol Sci 2006;41:21–30.10.1016/j.jdermsci.2005.11.002Suche in Google Scholar PubMed

39. Prüßmann W, Prüßmann J, Koga H, Recke A, Iwata H, Juhl D, et al. Prevalence of pemphigus and pemphigoid autoantibodies in the general population. Orphanet J Rare Dis 2015;10:63.10.1186/s13023-015-0278-xSuche in Google Scholar PubMed PubMed Central

40. Tampoia M, Giavarina D, Di Giorgio C. Diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-skin autoantibodies in autoimmune blistering skin diseases: a systematic review and meta-analysis. Autoimmun Rev 2012;12:121–6.10.1016/j.autrev.2012.07.006Suche in Google Scholar PubMed

41. Ide A, Hashimoto T, Amagai M, Tanaka M, Nishikawa T. Detection of autoantibodies against bullous pemphigoid and pemphigus antigens by an enzyme-linked immunosorbent assay using the bacterial recombinant proteins. Exp Dermatol 1995;4:112–6.10.1111/j.1600-0625.1995.tb00232.xSuche in Google Scholar PubMed

42. Nagel A, Lang A, Engel D, Podstawa E, Hunzelmann N, de Pita O, et al. Clinical activity of pemphigus vulgaris relates to IgE autoantibodies against desmoglein 3. Clin Immunol 2010;134:320–30.10.1016/j.clim.2009.11.006Suche in Google Scholar PubMed

43. Harman KE, Gratian MJ, Seed PT, Bhogal BS, Challacombe SJ, Black MM. Diagnosis of pemphigus by ELISA: a critical evaluation of two ELISAs for the detection of antibodies to the major pemphigus antigens, desmoglein 1 and 3. Clin Exp Dermatol 2000;25:236–40.10.1046/j.1365-2230.2000.00624.xSuche in Google Scholar PubMed

44. Weiss D, Ristl R, Griss J, Bangert C, Foedinger D, Stingl G, et al. Autoantibody levels and clinical disease severity in patients with pemphigus: comparison of aggregated anti-desmoglein ELISA values and indirect immunofluorescence titres. Acta Derm Venereol 2015;95:559–64.10.2340/00015555-2023Suche in Google Scholar PubMed

45. Ravi D, Prabhu SS, Rao R, Balachandran C, Bairy I. Comparison of immunofluorescence and desmoglein enzyme-linked immunosorbent assay in the diagnosis of pemphigus: a prospective, cross-sectional study in a tertiary care hospital. Indian J Dermatol 2017;62:171–7.10.4103/ijd.IJD_595_16Suche in Google Scholar PubMed PubMed Central

46. Witte M, Zillikens D, Schmidt E. Diagnosis of autoimmune blistering diseases. Front Med 2018;5:296.10.3389/fmed.2018.00296Suche in Google Scholar PubMed PubMed Central

47. Hebert V, Boulard C, Houivet E, Duvert Lehembre S, Borradori L, Della Torre R, et al. Large international validation of ABSIS and PDAI pemphigus severity scores. J Invest Dermatol 2019;139: 31–7.10.1016/j.jid.2018.04.042Suche in Google Scholar PubMed

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-1031).

Received: 2019-10-07
Accepted: 2020-03-03
Published Online: 2020-04-25
Published in Print: 2020-09-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood sampling for metanephrines: to stick or stick and wait?
  4. Review
  5. Glycan-specific antibodies as potential cancer biomarkers: a focus on microarray applications
  6. Mini Review
  7. Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis
  8. Opinion Papers
  9. The shift of the paradigm between ageing and diseases
  10. Managing COVID-19 outbreak in Nigeria: matters arising
  11. Circulating tumor DNA (ctDNA) is not a good proxy for liquid biopsies of tumor tissues for early detection
  12. General Clinical Chemistry and Laboratory Medicine
  13. Exact time of venous blood sample collection – an unresolved issue, on behalf of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE)
  14. Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results
  15. Interference of anti-streptavidin antibodies in immunoassays: a very rare phenomenon or a more common finding?
  16. Blood sampling for metanephrines comparing venipuncture vs. indwelling intravenous cannula in healthy subjects
  17. Volumetric absorptive microsampling and dried blood spot microsampling vs. conventional venous sampling for tacrolimus trough concentration monitoring
  18. Trueness evaluation and verification of inter-assay agreement of serum folate measuring systems
  19. Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache
  20. Comprehensive characterization and resolution of discrepant spectrophotometric bilirubin results in patients on eltrombopag therapy
  21. Influence of pancreatic status on circulating plasma sterols in patients with cystic fibrosis
  22. Influence of isotopically labeled internal standards on quantification of serum/plasma 17α-hydroxyprogesterone (17OHP) by liquid chromatography mass spectrometry
  23. Reference Values and Biological Variations
  24. The European Biological Variation Study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays
  25. Cardiovascular Diseases
  26. Comparison of the diagnostic performance with whole blood and plasma of four rapid antibody tests for SARS-CoV-2
  27. Infectious Diseases
  28. Exploring the possibilities of infrared spectroscopy for urine sediment examination and detection of pathogenic bacteria in urinary tract infections
  29. Letters to the Editors
  30. Towards the rational utilization of SARS-CoV-2 serological tests in clinical practice
  31. Response of anti-SARS-CoV-2 total antibodies to nucleocapsid antigen in COVID-19 patients: a longitudinal study
  32. Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: role of MPO specific activity in coronary artery disease
  33. The early antibody response to SARS-Cov-2 infection
  34. Laboratory work safety rules and guidelines during COVID-19 pandemic in Polish clinical laboratories – do our laboratories work according to a recent IFCC Taskforce Recommendations?
  35. Serum prealbumin deserves more significance in the early triage of COVID-19 patients
  36. Reference intervals for clinically reportable platelet parameters on the Mindray BC-6800Plus hematology analyzer
  37. A new method for monitoring harmonization of laboratory results within EQA schemes
  38. Potential serum magnesium under request in primary care. Laboratory interventions to identify patients with hypomagnesemia
  39. Interference from immunocomplexes on a high-sensitivity cardiac troponin T immunoassay
  40. Interleukin-6 chemiluminescent immunoassay on Lumipulse G600 II: analytical evaluation and comparison with three other laboratory analyzers
  41. Detection of Hb Phnom Penh by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry during the measurement of glycated hemoglobin
  42. Persistently increased vitamin B12 concentration due to cobalamin macrocomplexes: a case report and review of the literature
  43. Antidepressant use limits serotonin as a marker for neuroendocrine tumor disease activity by lowering of circulating serotonin concentrations
  44. Limitations of rapid diagnostic testing in the work-up of dengue infection – a case report
https://doi.org/10.1515/cclm-2019-1031
Schlagwörter für diesen Artikel
autoimmune bullous diseases; ELISA; IIF; pemphigus; pemphigoid

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood sampling for metanephrines: to stick or stick and wait?
  4. Review
  5. Glycan-specific antibodies as potential cancer biomarkers: a focus on microarray applications
  6. Mini Review
  7. Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis
  8. Opinion Papers
  9. The shift of the paradigm between ageing and diseases
  10. Managing COVID-19 outbreak in Nigeria: matters arising
  11. Circulating tumor DNA (ctDNA) is not a good proxy for liquid biopsies of tumor tissues for early detection
  12. General Clinical Chemistry and Laboratory Medicine
  13. Exact time of venous blood sample collection – an unresolved issue, on behalf of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE)
  14. Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results
  15. Interference of anti-streptavidin antibodies in immunoassays: a very rare phenomenon or a more common finding?
  16. Blood sampling for metanephrines comparing venipuncture vs. indwelling intravenous cannula in healthy subjects
  17. Volumetric absorptive microsampling and dried blood spot microsampling vs. conventional venous sampling for tacrolimus trough concentration monitoring
  18. Trueness evaluation and verification of inter-assay agreement of serum folate measuring systems
  19. Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache
  20. Comprehensive characterization and resolution of discrepant spectrophotometric bilirubin results in patients on eltrombopag therapy
  21. Influence of pancreatic status on circulating plasma sterols in patients with cystic fibrosis
  22. Influence of isotopically labeled internal standards on quantification of serum/plasma 17α-hydroxyprogesterone (17OHP) by liquid chromatography mass spectrometry
  23. Reference Values and Biological Variations
  24. The European Biological Variation Study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays
  25. Cardiovascular Diseases
  26. Comparison of the diagnostic performance with whole blood and plasma of four rapid antibody tests for SARS-CoV-2
  27. Infectious Diseases
  28. Exploring the possibilities of infrared spectroscopy for urine sediment examination and detection of pathogenic bacteria in urinary tract infections
  29. Letters to the Editors
  30. Towards the rational utilization of SARS-CoV-2 serological tests in clinical practice
  31. Response of anti-SARS-CoV-2 total antibodies to nucleocapsid antigen in COVID-19 patients: a longitudinal study
  32. Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: role of MPO specific activity in coronary artery disease
  33. The early antibody response to SARS-Cov-2 infection
  34. Laboratory work safety rules and guidelines during COVID-19 pandemic in Polish clinical laboratories – do our laboratories work according to a recent IFCC Taskforce Recommendations?
  35. Serum prealbumin deserves more significance in the early triage of COVID-19 patients
  36. Reference intervals for clinically reportable platelet parameters on the Mindray BC-6800Plus hematology analyzer
  37. A new method for monitoring harmonization of laboratory results within EQA schemes
  38. Potential serum magnesium under request in primary care. Laboratory interventions to identify patients with hypomagnesemia
  39. Interference from immunocomplexes on a high-sensitivity cardiac troponin T immunoassay
  40. Interleukin-6 chemiluminescent immunoassay on Lumipulse G600 II: analytical evaluation and comparison with three other laboratory analyzers
  41. Detection of Hb Phnom Penh by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry during the measurement of glycated hemoglobin
  42. Persistently increased vitamin B12 concentration due to cobalamin macrocomplexes: a case report and review of the literature
  43. Antidepressant use limits serotonin as a marker for neuroendocrine tumor disease activity by lowering of circulating serotonin concentrations
  44. Limitations of rapid diagnostic testing in the work-up of dengue infection – a case report
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 3.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2019-1031/html
Button zum nach oben scrollen