Boniotto Michele, Braida Laura, Baldas Valentina, Not Tarcisio, Ventura Alessandro, Vatta Serena, Radillo Oriano, Tedesco Francesco, Percopo Selvaggia, Montico Marcella, Amoroso Antonio, Crovella Sergio
Department of Sciences of Reproduction and Development, University of Trieste, Via dell'Istria 65/1, 34100 Trieste, Italy.
J Mol Med (Berl). 2005 Apr;83(4):308-15. doi: 10.1007/s00109-004-0623-3. Epub 2005 Jan 6.
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 alpha105, beta102 and DQ8 or alpha10301, beta10302) 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.
乳糜泻是一种多因素疾病，在具有遗传易感性的患者中，由摄入膳食麸质引起。关于遗传因素知之甚少，但两种HLA单倍型（DQ2或α105，β102以及DQ8或α10301，β10302）与该疾病有很强的关联。我们研究了编码甘露糖结合凝集素（MBL）的MBL2基因第一外显子多态性与乳糜泻之间的关系。此外，我们通过免疫组织化学和TUNEL法研究了MBL的作用。结果得到了临床发现的证实。我们招募了149名意大利乳糜泻患者；其中116名具有DQ2或DQ8特征。通过等位基因特异性PCR确定HLA单倍型，而通过熔解温度测定法解析MBL2基因型。对乳糜泻患者和健康对照的活检标本连续切片进行免疫组织化学和TUNEL检测。MBL2等位基因和基因型频率在乳糜泻患者和健康对照之间有显著差异。0等位基因的频率在DQ2或DQ8乳糜泻患者中为28%，在HLA非典型乳糜泻患者中为36%，在健康对照中为22%。有趣的是，MBL2 0/0基因型在33名HLA非典型乳糜泻患者中有7名（21%），在116名HLA典型乳糜泻患者中有13名（13%），但在147名健康对照中只有7名（5%）。此外，我们发现MBL2基因型与继发性自身免疫性疾病的发生密切相关。免疫组织化学和TUNEL结果支持MBL2在凋亡细胞清除中的作用。总之，导致MBL水平降低的MBL2变体与乳糜泻以及发生自身免疫性疾病的较高风险相关。在此我们提出MBL在该疾病中的作用，这可以很容易地应用于其他自身免疫性疾病。
