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Journal of Molecular Medicine

, Volume 83, Issue 4, pp 308–315 | Cite as

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

  • Michele Boniotto
  • Laura Braida
  • Valentina Baldas
  • Tarcisio Not
  • Alessandro Ventura
  • Serena Vatta
  • Oriano Radillo
  • Francesco Tedesco
  • Selvaggia Percopo
  • Marcella Montico
  • Antonio Amoroso
  • Sergio CrovellaEmail author
Original Article

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.

Keywords

Celiac disease Mannose binding lectin Polymorphisms Autoimmunity Apoptosis 

Abbreviations

CD

Celiac disease

H-W

Hardy-Weinberg

MBL

Mannose-binding lectin

TUNEL

Terminal deoxynucleotidyl transferase mediated nick end labeling

Notes

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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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Michele Boniotto
    • 1
    • 3
  • Laura Braida
    • 1
  • Valentina Baldas
    • 2
  • Tarcisio Not
    • 2
  • Alessandro Ventura
    • 2
  • Serena Vatta
    • 1
    • 3
  • Oriano Radillo
    • 4
  • Francesco Tedesco
    • 5
  • Selvaggia Percopo
    • 6
  • Marcella Montico
    • 7
  • Antonio Amoroso
    • 1
    • 3
  • Sergio Crovella
    • 1
    • 3
    Email author
  1. 1.Genetic Unit, Department of Sciences of Reproduction and DevelopmentUniversity of TriesteTriesteItaly
  2. 2.Pediatric Unit, Department of Sciences of Reproduction and DevelopmentChildren Hospital Burlo Garofolo, University of Triesteand TriesteItaly
  3. 3.Genetic ServiceChildren Hospital Burlo GarofoloTriesteItaly
  4. 4.Clinical Analysis LaboratoryChildren Hospital Burlo GarofoloTriesteItaly
  5. 5.Department of Physiology and PathologyUniversity of TriesteTriesteItaly
  6. 6.Pediatric DepartmentUniversity Federico IINaplesItaly
  7. 7.Epidemiology UnitChildren Hospital Burlo GarofoloTriesteItaly

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