@article {Doree000159, author = {Maria Pina Dore and Giovanni Mario Pes and Ivana Dettori and Vincenzo Villanacci and Alessandra Manca and Giuseppe Realdi}, title = {Clinical and genetic profile of patients with seronegative coeliac disease: the natural history and response to gluten-free diet}, volume = {4}, number = {1}, elocation-id = {e000159}, year = {2017}, doi = {10.1136/bmjgast-2017-000159}, publisher = {BMJ Specialist Journals}, abstract = {Objectives Patients with clinical, genetic and histological features of coeliac disease (CD), but negative for serological markers, pose a significant clinical problem. The aim of this study was to outline a specific profile, and to evaluate the natural history and response to gluten-free diet (GFD) of patients with seronegative CD.Methods patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA{\textendash}DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available.Results 48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA-DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42\% vs 22\%; p\<0.05). After a 1-year GFD trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative CD (25\%) experienced the occurrence of autoimmune diseases during a median follow-up of 133 months (range 72{\textendash}192).Conclusions Patients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.}, URL = {https://bmjopengastro.bmj.com/content/4/1/e000159}, eprint = {https://bmjopengastro.bmj.com/content/4/1/e000159.full.pdf}, journal = {BMJ Open Gastroenterology} }