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Cytokine genetic profile in Whipple’s disease

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European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Whipple’s disease (WD) is a very rare chronic systemic condition characterised by a Th2/T regulatory (Treg) dysregulated immune response versus Tropheryma whipplei, a bacterium widely diffuse in the environment. To investigate whether this Th2/Treg polarised response has a genetic background, we investigated the Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13 cytokine genes was analysed in 111 German and 22 Italian patients using the polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The frequencies of the genotypes, haplotypes and functional phenotypes were compared with those obtained in 201 German and 140 Italian controls. Clinical heterogeneity was also considered. Functionally, WD patients may be considered as low producers of TGF-β1, having an increased frequency of the genotype TGF-β1+869C/C,+915C/C [12.3 % vs. 3.81 %, odds ratio (OR) = 4.131, p = 0.0002] and high secretors of IL-4, carrying the genotype IL-4-590T/T (5.34 % vs. 1.17 %, OR = 5.09, p = 0.0096). No significant association was found between cytokine polymorphism and clinical variability. Analogously to the recent cellular findings of a Th2/Treg polarised response, we showed that the cytokine genetic profile of WD patients is skewed toward a Th2 and Treg response. This was similar in both German and Italian populations. However, the significant deviations versus the controls are poorer than that expected on the basis of these recent cellular findings.

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Acknowledgements

We are grateful to Susan West for reading and correcting the manuscript.

This project was funded by the Fifth Framework Programme of the European Commission (ref. QLG1-CT-2002-01049).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. First Department of Internal Medicine, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy

    F. Biagi, A. Marchese, L. Trotta, P. I. Bianchi, M. Di Stefano & G. R. Corazza

  2. Immunohematology and Transfusion Centre, IRCCS Foundation Policlinico San Matteo, Pavia, Italy

    C. Badulli, F. Garlaschelli, A. L. Cremaschi, L. Salvaneschi & M. Martinetti

  3. DRK Krankenhaus, Neuwied, Germany

    G. E. Feurle

  4. Universitätsklinik für Innere Medizin III, Klinische Abteilung Gastroenterologie und Hepatologie, Medizinische Universität Wien, Vienna, Austria

    C. Müller

  5. Medizinische Klinik I, CBF, Charité-Universitätsmedizin Berlin, Berlin, Germany

    V. Moos & T. Schneider

  6. Abteilung Innere Medizin, Krankenhaus Maria Hilf, Daun, Germany

    T. Marth

  7. Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany

    J. Mytilineos

  8. Biometry and Clinical Epidemiology, IRCCS Foundation Policlinico San Matteo, Pavia, Italy

    A. De Silvestri

  9. Coeliac Centre/1st Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, P.le Golgi, 19, 27100, Pavia, Italy

    F. Biagi

Authors
  1. F. Biagi
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  2. C. Badulli
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  3. G. E. Feurle
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  4. C. Müller
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  5. V. Moos
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  6. T. Schneider
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  7. T. Marth
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  8. J. Mytilineos
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  9. F. Garlaschelli
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  10. A. Marchese
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  11. L. Trotta
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  12. P. I. Bianchi
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  13. M. Di Stefano
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  14. A. L. Cremaschi
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  15. A. De Silvestri
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  16. L. Salvaneschi
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  17. M. Martinetti
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  18. G. R. Corazza
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Correspondence to F. Biagi.

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Biagi, F., Badulli, C., Feurle, G.E. et al. Cytokine genetic profile in Whipple’s disease. Eur J Clin Microbiol Infect Dis 31, 3145–3150 (2012). https://doi.org/10.1007/s10096-012-1677-8

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  • DOI: https://doi.org/10.1007/s10096-012-1677-8

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