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Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity

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Abstract

Background

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn’s disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting.

Aims

To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers.

Methods

TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed.

Results

UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001).

Conclusions

The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

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Acknowledgments

The authors would like to thank Dr. Maria Satra for expert technical assistance and Dr. Georgios Nasioulas for sequence analysis of clinical specimens. Grant support for the current project was offered by the Hellenic Society of Gastroenterology.

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Authors and Affiliations

  1. Department of Gastroenterology, University Hospital of Larissa, University of Thessaly, School of Medicine, 41110, Larissa, Greece

    Anastassios C. Manolakis, Andreas N. Kapsoritakis, Elisavet K. Tiaka, Konstantinos A. Oikonomou, Vassilis Lotis, Dimitra Vamvakopoulou, Ioanna Davidi & Spyros P. Potamianos

  2. Department of Medical Microbiology and Biochemistry, Amalia Fleming Hospital, 15127, Athens, Greece

    Anastasia Kapsoritaki

  3. Department of Molecular Biology and Genetics, University of Thessaly School of Medicine, 41110, Larissa, Greece

    Nikolaos Vamvakopoulos

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  1. Anastassios C. Manolakis
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Correspondence to Spyros P. Potamianos.

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Manolakis, A.C., Kapsoritakis, A.N., Kapsoritaki, A. et al. Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity. Dig Dis Sci 58, 371–380 (2013). https://doi.org/10.1007/s10620-012-2348-4

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