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01-08-2008 | Original Article

Serum antibodies against Saccharomyces cerevisiae: a new prognostic indicator in metastatic renal-cell carcinoma

Authors: Reinhold Ramoner, Andrea Rahm, Hubert Gander, Björn Stollenwerk, Claudia Falkensammer, Nicolai Leonhartsberger, Martin Thurnher

Published in: Cancer Immunology, Immunotherapy | Issue 8/2008

Abstract

Purpose

A recent study reported that a diet rich in bread and refined cereals might have an unfavorable role in the development of renal cell carcinoma (RCC). To test whether an underlying intolerance of bread ingredients is responsible for the unfavorable influence of bread on RCC, we examined patient sera for the presence of food-specific IgG.

Experimental design

A commercial test was used to detect food-specific IgG directed against a panel of 113 food antigens in sera of 54 patients with metastatic RCC. Kaplan–Meier estimates were used for univariate survival analysis, and differences in survival curves were assessed with the log-rank test. Multivariate survival analysis was done using a Cox regression model.

Results

We found that RCC patients with elevated serum levels of IgG antibodies against S. cerevisiae, commonly known as baker’s yeast and yet another bread component, have an unfavorable clinical course. Median survival of patients with high levels of S. cerevisiae IgG was only 17.8 months, whereas median survival of patients with low S. cerevisiae IgG was 43.8 months (P = 0.0022; log-rank). Multivariate survival analysis identified high levels of S. cerevisiae IgG as a strong and independent prognostic risk factor (risk ratio 4.6, P = 0.001; 95% CI 1.61–13.08).

Conclusions

Our findings indicate that serum levels of IgG against S. cerevisiae may predict survival in patients with metastatic RCC. The data suggest not cereals but baker’s yeast being the critical component of bread that may cause immune deviation and impaired immunosurveillance in predisposed RCC patients.

Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942–949PubMedCrossRef

Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8:639–646PubMedCrossRef

Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861PubMedCrossRef

Atkinson W, Sheldon TA, Shaath N, Whorwell PJ (2004) Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut 53:1459–1464PubMedCrossRef

Barta Z, Csipo I, Szabo GG, Szegedi G (2003) Seroreactivity against Saccharomyces cerevisiae in patients with Crohn’s disease and celiac disease. World J Gastroenterol 9:2308–2312PubMed

Berger S, Ballo H, Stutte HJ (1996) Immune complex-induced interleukin-6, interleukin-10 and prostaglandin secretion by human monocytes: a network of pro- and anti-inflammatory cytokines dependent on the antigen:antibody ratio. Eur J Immunol 26:1297–1301PubMedCrossRef

Berger S, Chandra R, Ballo H, Hildenbrand R, Stutte HJ (1997) Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes. Eur J Immunol 27:2994–3000PubMedCrossRef

Bossuyt X (2006) Serologic markers in inflammatory bowel disease. Clin Chem 52:171–181PubMedCrossRef

Bravi F, Bosetti C, Scotti L, Talamini R, Montella M, Ramazzotti V, Negri E, Franceschi S, La Vecchia C (2007) Food groups and renal cell carcinoma: a case–control study from Italy. Int J Cancer 120:681–685PubMedCrossRef

10.

Brugarolas J (2007) Renal-cell carcinoma—molecular pathways and therapies. N Engl J Med 356:185–187PubMedCrossRef

11.

Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353:2477–2490PubMedCrossRef

12.

Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D (1997) Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 3:797–801PubMedCrossRef

13.

Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836–848PubMedCrossRef

14.

Fowler JE Jr (1986) Failure of immunotherapy for metastatic renal cell carcinoma. J Urol 135:22–25PubMed

15.

Green PH, Jabri B (2006) Celiac disease. Annu Rev Med 57:207–221PubMedCrossRef

16.

Gripp S, Moeller S, Bolke E, Schmitt G, Matuschek C, Asgari S, Asgharzadeh F, Roth S, Budach W, Franz M, Willers R (2007) Survival prediction in terminally ill cancer patients by clinical estimates, laboratory tests, and self-rated anxiety and depression. J Clin Oncol 25:3313–3320PubMedCrossRef

17.

Holtl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C, Nussbaumer W, Falkensammer C, Bartsch G, Thurnher M (2005) Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother 54:663–670PubMedCrossRef

18.

Holtl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL, Coggin JH Jr, Thurnher M (2002) Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8:3369–3376PubMed

19.

Huang W, Na L, Fidel PL, Schwarzenberger P (2004) Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis 190:624–631PubMedCrossRef

20.

Kay AB (2001) Allergy and allergic diseases. First of two parts. N Engl J Med 344:30–37PubMedCrossRef

21.

Kleinrath T, Gassner C, Lackner P, Thurnher M, Ramoner R (2007) Interleukin-4 promoter polymorphisms: a genetic prognostic factor for survival in metastatic renal cell carcinoma. J Clin Oncol 25:845–851PubMedCrossRef

22.

Langowski JL, Kastelein RA, Oft M (2007) Swords into plowshares: IL-23 repurposes tumor immune surveillance. Trends Immunol 28:207–212PubMedCrossRef

23.

Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (2006) IL-23 promotes tumour incidence and growth. Nature 442:461–465PubMedCrossRef

24.

LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J, Reis e Sousa C (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8:630–638PubMedCrossRef

25.

Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM (1993) Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 178:187–196PubMedCrossRef

26.

Mejean A, Oudard S, Thiounn N (2003) Prognostic factors of renal cell carcinoma. J Urol 169:821–827PubMedCrossRef

27.

Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, Mazumdar M (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22:454–463PubMedCrossRef

28.

Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335:865–875PubMedCrossRef

29.

Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540PubMed

30.

Muller S, Styner M, Seibold-Schmid B, Flogerzi B, Mahler M, Konrad A, Seibold F (2005) Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn’s patients and are not inducible in murine models of colitis. World J Gastroenterol 11:6988–6994PubMed

31.

Negrier S, Perol D, Menetrier-Caux C, Escudier B, Pallardy M, Ravaud A, Douillard JY, Chevreau C, Lasset C, Blay JY (2004) Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6—from the Groupe Francais d’Immunotherapie. J Clin Oncol 22:2371–2378PubMedCrossRef

32.

Neurath MF (2007) IL-23: a master regulator in Crohn disease. Nat Med 13:26–28PubMedCrossRef

33.

Peeters M, Joossens S, Vermeire S, Vlietinck R, Bossuyt X, Rutgeerts P (2001) Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol 96:730–734PubMedCrossRef

34.

Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B, Charrier G, Targan SR, Colombel JF, Poulain D (1998) Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 42:788–791PubMedCrossRef

35.

Reiner SL (2007) Development in motion: helper T cells at work. Cell 129:33–36PubMedCrossRef

36.

Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C (2002) Structural basis for gluten intolerance in celiac sprue. Science 297:2275–2279PubMedCrossRef

37.

Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M, Tuma R, Ganea D (2007) The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23–>IL-17 axis. J Immunol 178:8138–8147PubMed

38.

Sollid LM, Jabri B (2005) Is celiac disease an autoimmune disorder? Curr Opin Immunol 17:595–600PubMedCrossRef

39.

Steinman L (2007) A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 13:139–145PubMedCrossRef

40.

Wierecky J, Muller MR, Wirths S, Halder-Oehler E, Dorfel D, Schmidt SM, Hantschel M, Brugger W, Schroder S, Horger MS, Kanz L, Brossart P (2006) Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res 66:5910–5918PubMedCrossRef

41.

Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J, Shellito JE, Bagby GJ, Nelson S, Charrier K, Peschon JJ, Kolls JK (2001) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194:519–527PubMedCrossRef

42.

Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D, Gitlitz BJ, deKernion JB, Figlin RA, Belldegrun AS (2001) Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol 19:1649–1657PubMed

Title: Serum antibodies against Saccharomyces cerevisiae: a new prognostic indicator in metastatic renal-cell carcinoma
Authors: Reinhold Ramoner
Andrea Rahm
Hubert Gander
Björn Stollenwerk
Claudia Falkensammer
Nicolai Leonhartsberger
Martin Thurnher
Publication date: 01-08-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0454-0

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