Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-20T00:04:21.788Z Has data issue: false hasContentIssue false
  • English
  • Français

Immune monitoring of Trichuris suis egg therapy in multiple sclerosis patients

Published online by Cambridge University Press:  15 August 2011

F. Benzel ,
H. Erdur ,
S. Kohler ,
M. Frentsch ,
A. Thiel ,
L. Harms ,
K.-P. Wandinger  and
B. Rosche
F. Benzel
Affiliation:
Department of Neurology & Experimental Neurology, Charité-Universitätsmedizin Berlin, Germany
H. Erdur
Affiliation:
Department of Neurology & Experimental Neurology, Charité-Universitätsmedizin Berlin, Germany
S. Kohler
Affiliation:
Department of Neurology & Experimental Neurology, Charité-Universitätsmedizin Berlin, Germany Berlin-Brandenburg Center of Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany
M. Frentsch
Affiliation:
Berlin-Brandenburg Center of Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany
A. Thiel
Affiliation:
Berlin-Brandenburg Center of Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany
L. Harms
Affiliation:
Department of Neurology & Experimental Neurology, Charité-Universitätsmedizin Berlin, Germany
K.-P. Wandinger
Affiliation:
Institute for Neuroimmunology and Clinical MS Research, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Eppendorf, Hamburg, Germany Institute for Experimental Immunology, affiliated with Euroimmun, Luebeck, Germany
B. Rosche*
Affiliation:
Department of Neurology & Experimental Neurology, Charité-Universitätsmedizin Berlin, Germany
*
*Fax: 0049-30 450560912 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Initial clinical trials using Trichuris suis eggs (TSO) in autoimmune diseases such as inflammatory bowel disease, revealed a striking suppressive effect on the autoimmune response. Here, we analysed the effect of TSO therapy on the course of multiple sclerosis (MS), as a Th1/Th17-associated autoimmune disease. Different immunological parameters in four patients with secondary progressive MS were surveyed during a 6-month therapy with TSO, focusing on the modulation of T-cell Th1–Th2 balance as well as on the innate immune response. We are able to show a slight downregulation of the Th1-associated cytokine pattern, especially relevant in interleukin (IL)-2 (P < 0.05 after 2 months of therapy), with a temporary increase of Th2-associated cytokines such as IL-4. Furthermore, mild eosinophily and changes in CD4+ and CD8+T cells and natural killer (NK) CD56 bright cell numbers were observed. The findings observed in this group of patients suggest that TSO therapy has a moderate immunomodulatory impact in MS.

Type
Research Papers
Information
Journal of Helminthology , Volume 86 , Issue 3 , September 2012 , pp. 339 - 347
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Araujo, M.I., Lopes, A.A., Medeiros, M., Cruz, A.A., Sousa-Atta, L., Sole, D. & Carvalho, E.M. (2000) Inverse association between skin response to aeroallergens and Schistosoma mansoni infection. International Archives of Allergy and Immunology 123, 145–148.CrossRefGoogle ScholarPubMed
Bager, P., Arnved, J., Ronborg, S., Wohlfahrt, J., Poulsen, L.K., Westergaard, T., Petersen, H.W., Kristensen, B., Thamsborg, S., Roepstorff, A., Kapel, C. & Melbye, M. (2010) Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. Journal of Allergy and Clinical Immunology 125, 123–130.CrossRefGoogle ScholarPubMed
Belkaid, Y., Sun, C.M. & Bouladoux, N. (2006) Parasites and immunoregulatory T cells. Current Opinion in Immunology 18, 406–412.CrossRefGoogle ScholarPubMed
Bielekova, B., Richert, N., Howard, T., Blevins, G., Markovic-Plese, S., McCartin, J., Frank, J.A., Wurfel, J., Ohayon, J., Waldmann, T.A., McFarland, H.F. & Martin, R. (2004) Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proceedings of the National Academy of Sciences USA 101, 8705–8708.CrossRefGoogle ScholarPubMed
Cooper, P.J. (2009) Interactions between helminth parasites and allergy. Current Opinion in Allergy and Clinical Immunology 9, 29–37.CrossRefGoogle ScholarPubMed
Correale, J. & Farez, M. (2007) Association between parasite infection and immune responses in multiple sclerosis. Annals of Neurology 61, 97–108.CrossRefGoogle ScholarPubMed
David, T., Thomas, C., Zaccone, P., Dunne, D.W. & Cooke, A. (2004) The impact of infection on the incidence of autoimmune disease. Current Topics in Medical Chemistry 4, 521–529.Google ScholarPubMed
Fleming, J.O. & Cook, T.D. (2006) Multiple sclerosis and the hygiene hypothesis. Neurology 67, 2085–2086.CrossRefGoogle ScholarPubMed
Graham, S.P., Trees, A.J., Collins, R.A., Moore, D.M., Guy, F.M., Taylor, M.J. & Bianco, A.E. (2001) Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis. Infection and Immunity 69, 4313–4319.CrossRefGoogle Scholar
Harnett, W. & Harnett, M.M. (2010) Helminth-derived immunomodulators: can understanding the worm produce the pill? Nature Reviews in Immunology 10, 278–284.CrossRefGoogle ScholarPubMed
Hartmann, S., Schonemeyer, A., Sonnenburg, B., Vray, B. & Lucius, R. (2002) Cystatins of filarial nematodes up-regulate the nitric oxide production of interferon-gamma-activated murine macrophages. Parasite Immunology 24, 253–262.CrossRefGoogle ScholarPubMed
Hirst, C., Ingram, G., Pickersgill, T., Swingler, R., Compston, D.A. & Robertson, N.P. (2009) Increasing prevalence and incidence of multiple sclerosis in South East Wales. Journal of Neurology, Neurosurgery and Psychiatry 80, 386–391.CrossRefGoogle ScholarPubMed
Kamradt, T., Goggel, R. & Erb, K.J. (2005) Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection. Trends in Immunology 26, 260–267.CrossRefGoogle ScholarPubMed
La Flamme, A.C., Ruddenklau, K. & Backstrom, B.T. (2003) Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infection and Immunity 71, 4996–5004.CrossRefGoogle ScholarPubMed
Lammie, P.J. & Katz, S.P. (1983) Immunoregulation in experimental filariasis. II. Responses to parasite and nonparasite antigens in jirds with Brugia pahangi. Journal of Immunology 130, 1386–1389.CrossRefGoogle ScholarPubMed
Maizels, R.M., Balic, A., Gomez-Escobar, N., Nair, M., Taylor, M.D. & Allen, J.E. (2004) Helminth parasites – masters of regulation. Immunological Reviews 201, 89–116.CrossRefGoogle ScholarPubMed
Mangan, N.E., van Rooijen, N., McKenzie, A.N. & Fallon, P.G. (2006) Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness. Journal of Immunology 176, 138–147.CrossRefGoogle ScholarPubMed
Panitch, H.S., Hirsch, R.L., Schindler, J. & Johnson, K.P. (1987) Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology 37, 1097–1102.CrossRefGoogle ScholarPubMed
Polman, C.H., Reingold, S.C., Edan, G., Filippi, M., Hartung, H.P., Kappos, L., Lublin, F.D., Metz, L.M., McFarland, H.F., O'Connor, P.W., Sandberg-Wollheim, M., Thompson, A.J., Weinshenker, B.G. & Wolinsky, J.S. (2005) Diagnostic criteria for multiple sclerosis: 2005 Revisions to the ‘McDonald Criteria’. Annals of Neurology 58, 840–846.CrossRefGoogle Scholar
Rocken, M., Racke, M. & Shevach, E.M. (1996) IL-4-induced immune deviation as antigen-specific therapy for inflammatory autoimmune disease. Immunology Today 17, 225–231.CrossRefGoogle ScholarPubMed
Ruyssers, N.E., De Winter, B.Y., De Man, J.G., Loukas, A., Herman, A.G., Pelckmans, P.A. & Moreels, T.G. (2008) Worms and the treatment of inflammatory bowel disease: are molecules the answer? Clinical and Developmental Immunology 2008, 567314.CrossRefGoogle ScholarPubMed
Satoguina, J., Mempel, M., Larbi, J., Badusche, M., Loliger, C., Adjei, O., Gachelin, G., Fleischer, B. & Hoerauf, A. (2002) Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microbes and Infection 4, 1291–1300.CrossRefGoogle Scholar
Scrivener, S., Yemaneberhan, H., Zebenigus, M., Tilahun, D., Girma, S., Ali, S., McElroy, P., Custovic, A., Woodcock, A., Pritchard, D., Venn, A. & Britton, J. (2001) Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet 358, 1493–1499.CrossRefGoogle Scholar
Sewell, D., Qing, Z., Reinke, E., Elliot, D., Weinstock, J., Sandor, M. & Fabry, Z. (2003) Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. International Immunology 15, 59–69.CrossRefGoogle ScholarPubMed
Smits, H.H., Hammad, H., van Nimwegen, M., Soullie, T., Willart, M.A., Lievers, E., Kadouch, J., Kool, M., Kos-van Oosterhoud, J., Deelder, A.M., Lambrecht, B.N. & Yazdanbakhsh, M. (2007) Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection. Journal of Allergy and Clinical Immunology 120, 932–940.CrossRefGoogle ScholarPubMed
Sospedra, M. & Martin, R. (2005) Immunology of multiple sclerosis. Annual Review of Immunology 23, 683–747.CrossRefGoogle ScholarPubMed
Strachan, D.P. (1989) Hay fever, hygiene, and household size. British Medical Journal 299, 1259–1260.CrossRefGoogle ScholarPubMed
Summers, R.W., Elliott, D.E., Qadir, K., Urban, J.F. Jr, Thompson, R. & Weinstock, J.V. (2003) Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. American Journal of Gastroenterology 98, 2034–2041.CrossRefGoogle ScholarPubMed
Summers, R.W., Elliott, D.E., Urban, J.F. Jr, Thompson, R. & Weinstock, J.V. (2005) Trichuris suis therapy in Crohn's disease. Gut 54, 87–90.CrossRefGoogle ScholarPubMed
Wilson, M.S., Taylor, M.D., Balic, A., Finney, C.A., Lamb, J.R. & Maizels, R.M. (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. The Journal of Experimental Medicine 202, 1199–1212.CrossRefGoogle ScholarPubMed
Yazdanbakhsh, M., van den Biggelaar, A. & Maizels, R.M. (2001) Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends in Immunology 22, 372–377.CrossRefGoogle ScholarPubMed
Zaccone, P., Fehervari, Z., Jones, F.M., Sidobre, S., Kronenberg, M., Dunne, D.W. & Cooke, A. (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. European Journal of Immunology 33, 1439–1449.CrossRefGoogle ScholarPubMed