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Evidence of a correlation between mannose binding lectin and celiac disease: a model for other autoimmune diseases

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Abstract

Celiac disease is a multifactorial disorder caused, in genetically susceptible patients, by the ingestion of dietary gluten. Very little is known about the genetic factors, but there is a strong association of two HLA haplotypes (DQ2 or α1*05, β1*02 and DQ8 or α1*0301, β1*0302) with the disease. We investigated the relationship between polymorphisms in the first exon of the MBL2 gene, which encodes for mannose binding lectin (MBL) and celiac disease. Moreover we studied the MBL role by immunohistochemistry and TUNEL. Results were confirmed by clinical findings. We enrolled 149 Italian celiac patients; 116 were characterized by the presence of DQ2 or DQ8. The HLA haplotype was established by allelic specific PCR while the MBL2 genotype was resolved by melting temperature assay. Immunohistochemistry and TUNEL assays were performed on serial sections of biopsy specimens from celiac patients and healthy controls. MBL2 allele and genotype frequencies varied significantly between celiac patients and healthy controls. The frequencies of the 0 allele were 28% in DQ2 or DQ8 celiac patients, 36% in HLA atypical celiac patients, and 22% in healthy controls. Interestingly, the MBL2 0/0 genotype was present in 7 of 33 HLA atypical celiac patients (21%) and in 13 of 116 HLA typical celiac patients (13%) but in only 7 of 147 healthy controls (5%). Furthermore, we found that MBL2 genotype is strongly associated with the occurrence of secondary autoimmune diseases. Immunohistochemistry and TUNEL findings support a role of MBL2 in the clearance of apoptotic cells. In conclusion, MBL2 variants, responsible for lower MBL levels, are associated with celiac disease and higher risk of developing autoimmune diseases. Here we propose a role for MBL in the disease which could be easily applied to other autoimmune disorders.

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Fig. 1

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Abbreviations

CD :

Celiac disease

H-W :

Hardy-Weinberg

MBL :

Mannose-binding lectin

TUNEL :

Terminal deoxynucleotidyl transferase mediated nick end labeling

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Acknowledgements

This work was supported by a grant (PRIN 2002) from the Italian Ministry of Research by grant RC 2004 03/04 from the Italian Ministry of Health and by EU Concerted Action Contract No. QLGI-CT-2001-01039). M.B. is the recipient of a long-term fellowship from Trieste University. The authors thank Dr. Citta for helping in the preparation of biopsy specimens and slides used for immunohistochemistry and TUNEL experiments.

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Authors and Affiliations

  1. Genetic Unit, Department of Sciences of Reproduction and Development, University of Trieste, Via dell’Istria 65/1, 34100, Trieste, Italy

    Michele Boniotto, Laura Braida, Serena Vatta, Antonio Amoroso & Sergio Crovella

  2. Pediatric Unit, Department of Sciences of Reproduction and Development, Children Hospital Burlo Garofolo, University of Triesteand , Via dell’Istria 65/1, 34100, Trieste, Italy

    Valentina Baldas, Tarcisio Not & Alessandro Ventura

  3. Genetic Service, Children Hospital Burlo Garofolo, Via dell’Istria 65/1, 34100, Trieste, Italy

    Michele Boniotto, Serena Vatta, Antonio Amoroso & Sergio Crovella

  4. Clinical Analysis Laboratory, Children Hospital Burlo Garofolo, Via dell’Istria 65/1, 34100, Trieste, Italy

    Oriano Radillo

  5. Department of Physiology and Pathology, University of Trieste, Piazzale Europa 1, 34100, Trieste, Italy

    Francesco Tedesco

  6. Pediatric Department, University Federico II, Via Pansini 5, 80131, Naples, Italy

    Selvaggia Percopo

  7. Epidemiology Unit, Children Hospital Burlo Garofolo, Via dell’Istria 65/1, 34100, Trieste, Italy

    Marcella Montico

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  1. Michele Boniotto
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  2. Laura Braida
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  3. Valentina Baldas
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  4. Tarcisio Not
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  5. Alessandro Ventura
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  10. Marcella Montico
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  11. Antonio Amoroso
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  12. Sergio Crovella
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Corresponding author

Correspondence to Sergio Crovella.

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Boniotto, M., Braida, L., Baldas, V. et al. Evidence of a correlation between mannose binding lectin and celiac disease: a model for other autoimmune diseases. J Mol Med 83, 308–315 (2005). https://doi.org/10.1007/s00109-004-0623-3

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  • DOI: https://doi.org/10.1007/s00109-004-0623-3

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