Boström Michaela, Brundin Charlotte, Björck Sara, Agardh Daniel
Celiac Disease and Diabetes Unit, Lund University, Malmö, Sweden.
J Pediatr Gastroenterol Nutr. 2024 May;78(5):1143-1148. doi: 10.1002/jpn3.12181. Epub 2024 Mar 13.
Autoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen (HLA)-genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years.
Included were 13,860 HLA-DQ-genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA-DQB102 and/or DQB103:02 (HLA-risk) children were compared with non-HLA-DQB102 and non-DQB103:02 (HLA-nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody-positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease.
At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA-risk children compared with 0/1824 HLA-nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA-risk children compared with 0/2167 HLA-nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA-risk children positive for IgA-tTG and/or IgG-tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%-1.7%) HLA-risk children were diagnosed with celiac disease compared with 0/1303 HLA-nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age.
Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.
抗组织转谷氨酰胺酶（tTG）自身抗体是乳糜泻的血清学标志物。本研究旨在探讨人类白细胞抗原（HLA）基因分型和tTG自身抗体在一个随访至15岁的纵向出生队列中筛查乳糜泻的适用性。
研究纳入了13860名出生时进行了HLA-DQ基因分型的儿童，他们之前分别被邀请在3岁和9岁时进行筛查。将携带HLA-DQB102和/或DQB103:02（HLA风险型）的儿童与不携带HLA-DQB102和DQB103:02（HLA非风险型）的儿童进行比较。本研究在这些儿童15岁时再次邀请了12948/13860（93.4%）名儿童，其中1056/2374（44.5%）名儿童在3岁和9岁时均参与了筛查。采用放射结合试验分别分析了抗tTG的免疫球蛋白A（IgA）和G（IgG）自身抗体。对持续tTG自身抗体阳性的儿童进行肠道活检以确诊乳糜泻。
3岁时，1635名HLA风险型儿童中有56名（3.4%）被诊断为乳糜泻，而1824名HLA非风险型儿童中无1例确诊（p<0.001）。到9岁时，1910名HLA风险型儿童中有72名（3.8%）被诊断为乳糜泻，而2167名HLA非风险型儿童中无1例确诊（p<0.001）。15岁时的筛查发现，1071名HLA风险型儿童中有14名（1.3%）IgA-tTG和/或IgG-tTG呈阳性，其中12/1071（1.1%）持续呈阳性。在这些儿童中，10/1071（0.9%，95%置信区间：0.4%-1.7%）名HLA风险型儿童被诊断为乳糜泻，而1303名HLA非风险型儿童中无1例确诊（p<0.001），5/491（1.0%）在3岁和9岁时筛查均为阴性。
乳糜泻筛查需要在多个时间点进行，以发现所有病例，但可仅限于HLA风险型儿童。
