Tissue transglutaminase autoantibodies and human leucocyte antigen in Down’s syndrome patients with coeliac disease D Agardh 1,2 , A Nilsson 2 , A Carlsson 3 , I Kockum 4 ,A Ê Lernmark 2,5 and S-A Ivarsson 1 Department of Paediatrics 1 and Department of Endocrinology , Wallenberg Laboratory 2 , Malmo ¨ University Hospital, Malmo ¨, Sweden; Department of Paediatrics 3 , Lund University Hospital, Lund University, Lund, Sweden; Department of Molecular Medicine 4 , Karolinska Institutet , Stockholm, Sweden; RH Williams Laboratory 5 , Department of Medicine, University of Washington , Seattle, USA Agardh D, Nilsson A, Carlsson A, Kockum I, Lernmark A Ê , Ivarsson S-A. Tissue transglutaminase autoantibodies and HLA in Down’s syndrome patients with coeliac disease. Acta Pædiatr 2002; 91: 34–38. Stockholm. ISSN 0803-5253 The association between autoantibodies against tissue transglutaminase (tTG) and human leucocyte antigen (HLA)-DQB1 alleles was tested in Down’s syndrome (DS) patients with and without coeliac disease (CD). Immunoglobulin A (IgA) and G (IgG) anti-tTG were measured in radioligand binding assays and compared with conventionally analysed IgA antibodies against gliadin (AGA) and IgA autoantibodies against endomysium (EMA) in 48 DS patients. HLA-DQB1 typing was carried out by polymerase chain reaction and hybridization with allele-specic probes in 41/48 patients. Both IgA-tTG and IgG-tTG, as well as EMA, were detected in 7/48 and AGA in 15/48 patients. Intestinal biopsy showed histopathological changes consistent with CD in 9/16 patients. HLA-DQB1 typing, available for 8/9 patients with and for 33/39 without CD, demonstrated that 5/8 with CD had DQB1*02 compared with 7/33 of those without (p = 0.0345). In patients with anti-tTG, 5/6 had the DQB1*02 allele compared with 7/35 of those without (p = 0.0053). Conclusions: Anti-tTG are HLA-DQB1*02-associated autoantibodies which together could be useful screening tests for silent CD in DS patients. In patients with gastrointestinal symptoms or clinical signs of malabsorption, anti-tTG should be combined with AGA to detect other forms of enteropathies and CD. Key words: AGA, EMA, HLA-DQB1*02, tissue transglutaminase D Agardh, Department of Paediatrics, Malmo ¨ University Hospital, SE-205 02 Malmo ¨, Sweden (Tel. ‡46 40 33 10 00, fax. ‡46 40 33 70 42, e-mail. daniel.agardh@home.se) Coeliac disease (CD) is a common enteropathy caused by a T-cell-mediated response to gliadin in dietary gluten leading to villous atrophy, crypt hyperplasia and damage to the surface epithelium of the small bowel (1). The prevalence of CD varies between different popula- tions and regions, but it is particularly common among Swedish children (2). For unknown reasons, CD is even more prevalent in patients with Down’s syndrome (DS) (3–8) and Turner’s syndrome (9) than in the general population. Apart from CD, DS patients are also prone to develop type I diabetes (10) and autoimmune thyroiditis (11). It is well known that a majority of the CD patients carry the human leucocyte antigen (HLA)- DQ2 haplotype (encoded by the DQA1*0501 and DQB1*02 alleles), and the remainder the DQ8 haplo- type (the DQA1*0301 and DQB1*0302 alleles) (12). In DS patients, CD has been associated with DQ2 (3) and DQA1*0101 (4), and a repeated serological screening procedure has been proposed in DS patients with DQA1*0501-DQB1*02 (13). Immunoglobulin A (IgA) antibodies against gliadin (AGA) and IgA autoantibodies against endomysium (EMA) are serological markers for CD. Gluten has been known for decades as the triggering antigen, while tissue transglutaminase (tTG) was recently identied as the major EMA autoantigen (14). In contrast to EMA, autoantibodies against tissue transglutaminase (anti- tTG) can be detected in enzyme-linked immunosorbent assays (ELISAs) and in radioligand binding assays (RBAs). Both methods allow quantitative and reprodu- cible analysis of autoantibodies and it has been shown that IgA-tTG (15) and IgG-tTG (16) are sensitive serological markers for CD. The aim of the present study was to determine the prevalence of CD among HLA-DQB1 typed DS patients by measuring both IgA-tTG and IgG-tTG in relation to AGA, EMA and intestinal biopsies in antibody-positive patients. The hypothesis was that the increased propensity for autoimmunity in DS patients would be associated with HLA-DQB1*02 and an increased antibody frequency to CD antigens also in DS patients with silent CD. Ó 2002 Taylor & Francis. ISSN 0803-5253 Acta Pñdiatr 91: 34±38. 2002