Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden; Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Clin Gastroenterol Hepatol. 2015 Jul;13(7):1271-1277.e2. doi: 10.1016/j.cgh.2015.01.026. Epub 2015 Jan 31.
BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease.
We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups.
During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P = .11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation.
First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.
患有乳糜泻的个体的一级亲属患这种疾病的风险增加，但对于他们患其他自身免疫性疾病的风险知之甚少。我们评估了乳糜泻患者的一级亲属和配偶患非乳糜泻自身免疫性疾病的风险。
我们通过搜索 28 个瑞典病理学部门在 1969 年至 2008 年期间收集的十二指肠和空肠活检，来确定乳糜泻患者。根据绒毛萎缩的活检报告（等于 Marsh 分级 3；n=29096）确定乳糜泻。将乳糜泻患者与多达 5 名性别、年龄、县和日历年份匹配的对照（无乳糜泻患者）（总计 144522 名对照）相匹配。通过瑞典医疗保健登记处，我们确定了乳糜泻患者（n=84648）及其对照（n=430942）的所有一级亲属（父亲、母亲、兄弟姐妹和后代）和配偶。我们使用 Cox 回归分析计算这些组中非乳糜泻自身免疫性疾病（克罗恩病、1 型糖尿病、甲状腺功能减退症、甲状腺功能亢进症、银屑病、类风湿关节炎、结节病、系统性红斑狼疮或溃疡性结肠炎）的风险比（HR）。
在随访期间（中位数 10.8 年），3333 名乳糜泻患者的一级亲属（3.9%）和 12860 名对照的一级亲属（3.0%）患有除乳糜泻以外的自身免疫性疾病。与对照相比，乳糜泻患者的一级亲属患非乳糜泻自身免疫性疾病的风险增加（HR，1.28；95%置信区间，1.23-1.33），配偶也如此（HR，1.20；95%置信区间，1.06-1.35）。乳糜泻患者的一级亲属和配偶患非乳糜泻自身免疫性疾病的风险估计值之间没有差异（交互检验：P=0.11）。在随访评估的前 2 年内，非乳糜泻自身免疫性疾病的 HR 最高。
乳糜泻患者的一级亲属和配偶患非乳糜泻自身免疫性疾病的风险增加。除遗传因素外，环境因素和确定偏差可能导致乳糜泻患者一级亲属自身免疫的风险增加。
