The role of flow cytometry in celiac disease screening using human leukocyte antigen in adult patients with type 1 diabetes mellitus

Miren VicuÃ±a Arregui; Jose Manuel Zozaya Urmeneta; Helena LeÃ³n Brito; Juan Pablo MartÃ­nez De Esteban; Carlos Prieto MartÃ­nez; Lluis Forga Llenas; Erkuden Aranburu Urtasun; Francisco Sala Pericas; RamÃ³n AngÃ³s Musgo; Maria Rosario Mercado Gutierrez; Mercedes Palacios Sarrasqueta

Authors Miren VicuÃ±a Arregui, Jose Manuel Zozaya Urmeneta, Helena LeÃ³n Brito, Juan Pablo MartÃnez De Esteban, Carlos Prieto MartÃnez, Lluis Forga Llenas, Erkuden Aranburu Urtasun, Francisco Sala Pericas, RamÃ³n AngÃ³s Musgo, Maria Rosario Mercado Gutierrez, Mercedes Palacios Sarrasqueta.

Abstract

Background Patients with type 1 diabetes mellitus (DM1) have an increased risk of celiac disease (CD). Since CD can be seronegative, more sensible tests for detection are needed. In seronegative patients, CD diagnosis may be difficult because of a lack of specificity. Flow cytometry analysis of lymphocyte populations can be useful in this situation. We aimed to study the prevalence of CD in adult DM1 using human leukocyte antigen (HLA) compatibility-based screening. A secondary goal was to study the role of flow cytometry as a complementary tool in these patients.

Methods We selected 200 patients with DM1, of whom 190 (95%) had HLA DQ2, DQ8 or both. Of these, 136 agreed to participate and provided epidemiological data. All patients underwent blood tests and gastroscopy.

Results Sixteen patients had a histology consistent with CD. After ruling out other diagnoses, 6 patients were diagnosed with CD, 2 of whom had negative antibodies. All were DQ2.5 homozygous, with a CD prevalence of 9.8% in this group. In the flow cytometry analysis of duodenal biopsy samples, when we compared all non-CD with CD patients, we found that the Î³/Î´ intraepithelial lymphocyte (IEL) percentage was significantly higher and the CD3 negative IEL percentage significantly lower in the CD group. We found similar results when we compared only those with histological lesions.

Conclusions Screening of CD in patients with DM1 by HLA detects only 1% of seronegative patients with CD. DQ2.5 homozygous patients are at most risk of developing CD. The study of lymphocyte populations in the duodenal biopsy by flow cytometry discriminates patients with CD from those without CD with high sensitivity and specificity.

Keywords Celiac disease, flow cytometry, HLA typing, type 1 diabetes mellitus

Ann Gastroenterol 2017; 30 (2): 179-185