Prevalence of Celiac disease among first and second digree relatives in the U.S.A

Introduction: Large epidemiological studies showed a high prevalence (1:300) of Celiac disease (CD) throughout Europe. In contrast, CD is still considered rare in U.S.A. although our blood donor screening study suggested a prevalence similar to that reported in Europe(1). Aims of this study were: 1. To establish the prevalence of CD among first and second degree relatives of celiac patients in U.S.A. and, 2. To compare the sensitivity and specificity of transglutaminase (tTG) assay to the antiendomysium antibodies (EmA) test. Methods: Informed consent was obtained from 746 first degree, and 110 second degree relatives of CD subjects recruited through local celiac support groups. A questionnaire was used to collect relationship and medical data from all subjects. Ema IgA antibodies were detected in sera by indirect immunofluorescence (IFA) using both human umbilical cord vein and monkey esophagus cryosections as substrate. IgA and IgG antigliadin (AGA) antibodies were detected using an ELISA method. IgG AGA positive sera were also tested for total IgA level. All Ema-positive and a subgroup of Ema-negative samples were also tested for IgA and IgG anti-tTG by ELISA. Intestinal endoscopy and biopsy was recommended to all subjects with positive Ema test and/or elevated AGA, and to subjects AGA IgG positive with total IgA deficiency. Results: The results summarized in the table show that 35/746 (4.7%) first degree relatives were EmA positive. In 8 of them, intestinal biopsy was performed and showed a flat mucosa. Five of the twenty-four first degree relatives that had elevated IgA and IgG AGA underwent to intestinal biopsy. Three of them (60%) showed partial villous atrophy. Four out of 110 (3.6%) second degree relatives were EmA positive. Comparison of EmA-positive sera with anti-tTG assay revealed a sensitivity of 91% for IgA and 71% for IgG. EmA-negative samples were also tested for IgA and IgG anti-tTG. 316/323 were IgA anti-tTG negative (specificity 98%) and 312/323 were IgG anti-tTG negative (specificity 96.4%). n AGA AGA AGA EmA+ Anti-tTG Anti-tTG Biopsy+ IgA+ IgG+ IgA&IgG+ IgA+ IgG+ I 746 51 118 (6 total 24 35 30 19 13 degree IgA deficient) II 110 4 13 (0 total 2 4 2 3 - degree IgA deficient) 856 55 131 26 39 32 22 Discussion: Our data show a projected high prevalence of CD among first (6.3%) and second (6.6%) degree relatives of U.S. patients. IgA Ema and IgA anti-tTG antibodies have a predictive positive value of 100%. Besides, in 60% of subjects AGA + that underwent intestinal biopsy, we found histologic features of celiac disease, even if the mucosal lesion was moderate. In our study tissue tTG autoantibodies are highly sensitive (IgA: 91%; IgG 76%) and specific (IgA 98%; IgG 96.4%) indicators for untreated CD and represent a valuable objective test to diagnose this condition.