Stene Lars C, Honeyman Margo C, Hoffenberg Edward J, Haas Joel E, Sokol Ronald J, Emery Lisa, Taki Iman, Norris Jill M, Erlich Henry A, Eisenbarth George S, Rewers Marian
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045-6511, USA.
Am J Gastroenterol. 2006 Oct;101(10):2333-40. doi: 10.1111/j.1572-0241.2006.00741.x.
Few studies have assessed the role of specific gastrointestinal infections in celiac disease. We investigated whether increased frequency of rotavirus infection, a common cause of gastrointestinal infection and inflammation, predicts increased risk of celiac disease autoimmunity.
A cohort of 1,931 children from the Denver metropolitan area who carried celiac disease human leukocyte antigen (HLA) risk alleles were followed from infancy for development of celiac disease autoimmunity, defined as positivity at two or more subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies measured using a radioimmunoassay with human recombinant tTG. Blood samples were obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus antibodies were assayed using an indirect enzyme immunoassay in serial serum samples from each case and two matched controls. Frequency of infections were estimated by the number of increases (> 2 assay coefficient of variation) in rotavirus antibody between clinic visits.
Fifty-four cases developed celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent rotavirus infections predicted a higher risk of celiac disease autoimmunity (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI] 0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for > or = 2 infections, rate ratio for trend per increase in number of infections = 1.94, 95% CI 1.04-3.61, p = 0.037). The result was similar after adjustment for gender, ethnic group, maternal education, breast-feeding, day-care attendance, number of siblings, season of birth, and number of HLA DR3-DQ2 haplotypes.
This prospective study provides the first indication that a high frequency of rotavirus infections may increase the risk of celiac disease autoimmunity in childhood in genetically predisposed individuals.
很少有研究评估特定胃肠道感染在乳糜泻中的作用。我们调查了轮状病毒感染（胃肠道感染和炎症的常见病因）频率增加是否预示着乳糜泻自身免疫风险增加。
对来自丹佛市区的1931名携带乳糜泻人类白细胞抗原（HLA）风险等位基因的儿童进行队列研究，从婴儿期开始跟踪其乳糜泻自身免疫的发展情况，乳糜泻自身免疫定义为使用人重组组织转谷氨酰胺酶（tTG）的放射免疫测定法在随后两次或更多次门诊就诊时组织转谷氨酰胺酶（tTG）自身抗体呈阳性。在9、15和24个月龄时采集血样，此后每年采集一次。使用间接酶免疫测定法检测每个病例及两个匹配对照的系列血清样本中的轮状病毒抗体。通过门诊就诊期间轮状病毒抗体增加的次数（>2个检测变异系数）来估计感染频率。
54例在中位年龄4.4岁时出现乳糜泻自身免疫。36例进行了肠道活检，其中27例（75%）乳糜泻检测呈阳性。频繁的轮状病毒感染预示着乳糜泻自身免疫风险更高（与零感染相比，一次感染的率比为1.94，95%置信区间[CI]0.39 - 9.56，≥2次感染的率比为3.76，95%CI 0.76 - 18.7，感染次数每增加一次的趋势率比 = 1.94，95%CI 1.04 - 3.61，p = 0.037）。在对性别、种族、母亲教育程度、母乳喂养、日托情况、兄弟姐妹数量、出生季节和HLA DR3 - DQ2单倍型数量进行调整后，结果相似。
这项前瞻性研究首次表明，在具有遗传易感性的个体中，轮状病毒感染频率高可能会增加儿童期乳糜泻自身免疫的风险。
