Lakatos P L, Altorjay I, Mándi Y, Lakatos L, Tumpek J, Kovacs A, Molnar T, Tulassay Z, Miheller P, Palatka K, Szamosi T, Fischer S, Papp J, Papp M
1st Department of Medicine, Semmelweis University, Budapest, Hungary.
Tissue Antigens. 2008 Jun;71(6):552-9. doi: 10.1111/j.1399-0039.2008.01049.x. Epub 2008 Apr 7.
Antibodies against different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn's disease (CD). Recently, an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in various genes other than NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Three hundred and seventy-six well-characterized, unrelated, consecutive CD patients (male/female: 191/185, age at onset: 29.1 +/- 12.9 years, duration: 7.9 +/- 11.7 years) were investigated. Sera were assayed for anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCAs) immunoglobulin (Ig) A and IgG, and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by polymerase chain reaction-restriction fragment length polymorphism, and DEFB1 was genotyped in a subgroup of 160 patients. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. The carriage of DEFB1 20A variant alleles less frequently led to antiglycan positivity compared with patients without (29.6% vs 46.2%, OR: 0.49, 95% CI: 0.25-0.97), regardless of disease location or behavior. Similar tendency was observed for DEFB1 44G (present: 21.6% vs absent: 10.2%, P = 0.06) and ALCA. A gene or serology dosage effect was not observed. However, no association was found between the DEFB1 G52A, DLG5 R30Q, and NOD1/CARD4 E266K variants and any of the serology markers. We found that variants in human beta-defensin 1 gene are inversely associated with antiglycan antibodies, further confirming an important role for innate immunity in the pathogenesis of CD.
针对不同微生物表位的抗体与疾病表型相关，可能具有诊断意义，且可能反映克罗恩病（CD）中耐受性的丧失。最近，有报道称这些抗体的存在与模式识别受体基因的突变之间存在关联。我们的目的是研究除与CD相关的NOD2/CARD15或TLR4之外的各种基因（NOD1/CARD4、DLG5和DEFB1）中的突变是否会影响匈牙利一组CD患者中针对细菌蛋白和碳水化合物的抗体的存在情况。对376例特征明确、无亲缘关系、连续入选的CD患者（男/女：191/185，发病年龄：29.1±12.9岁，病程：7.9±11.7年）进行了研究。检测血清中的抗Omp、抗酿酒酵母抗体（ASCA）免疫球蛋白（Ig）A和IgG，以及针对酿酒酵母甘露聚糖表位（gASCA）、层连二糖苷（ALCA）、壳二糖苷（ACCA）和甘露二糖苷（AMCA）的抗体。通过聚合酶链反应-限制性片段长度多态性检测NOD1/CARD4、DLG5和DEFB1变异，在160例患者的亚组中对DEFB1进行基因分型。通过查阅患者病历确定详细的临床表型。与未携带DEFB1 20A变异等位基因的患者相比，携带该变异等位基因的患者抗聚糖阳性的频率更低（29.6%对46.2%，OR：0.49，9
