Intestinal Intraepithelial Lymphocyte Cytometric Pattern Is More Accurate than Subepithelial Deposits of Anti-Tissue Transglutaminase IgA for the Diagnosis of Celiac Disease in Lymphocytic Enteritis

Abstract

Background & AimsAn increase in CD3+TCRγδ+ and a decrease in CD3− intraepithelial lymphocytes (IEL) is a characteristic flow cytometric pattern of celiac disease (CD) with atrophy. The aim was to evaluate the usefulness of both CD IEL cytometric pattern and anti-TG2 IgA subepithelial deposit analysis (CD IF pattern) for diagnosing lymphocytic enteritis due to CD.MethodsTwo-hundred and five patients (144 females) who underwent duodenal biopsy for clinical suspicion of CD and positive celiac genetics were prospectively included. Fifty had villous atrophy, 70 lymphocytic enteritis, and 85 normal histology. Eight patients with non-celiac atrophy and 15 with lymphocytic enteritis secondary to Helicobacter pylori acted as control group. Duodenal biopsies were obtained to assess both CD IEL flow cytometric (complete or incomplete) and IF patterns.ResultsSensitivity of IF, and complete and incomplete cytometric patterns for CD diagnosis in patients with positive serology (Marsh 1+3) was 92%, 85 and 97% respectively, but only the complete cytometric pattern had 100% specificity. Twelve seropositive and 8 seronegative Marsh 1 patients had a CD diagnosis at inclusion or after gluten free-diet, respectively. CD cytometric pattern showed a better diagnostic performance than both IF pattern and serology for CD diagnosis in lymphocytic enteritis at baseline (95% vs 60% vs 60%, p = 0.039).ConclusionsAnalysis of the IEL flow cytometric pattern is a fast, accurate method for identifying CD in the initial diagnostic biopsy of patients presenting with lymphocytic enteritis, even in seronegative patients, and seems to be better than anti-TG2 intestinal deposits.

High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies

“…21 However, it has been reported that analysis of the intraepithelial intestinal lymphocyte flow cytometric pattern is an accurate method for identifying CD in the initial diagnostic biopsy of seronegative patients presenting with lymphocytic enteritis, and it seems to be better than antiÀtissue transglutaminase 2 intestinal deposits. 22 Therefore, a more accurate evaluation of the duodenal histology, using this method, should be recommended in all NCWS patients that show the DQ2 or the DQ8 haplotypes and duodenal lymphocytosis.…”

Gamma delta+ intraepithelial lymphocytes and coeliac lymphogram in a diagnostic approach to coeliac disease in patients with seronegative villous atrophy

“…The use of these unified cut‐offs did not change the classification of the intraepithelial lymphocyte pattern in any patient with respect to the previous one. There were four intraepithelial lymphocyte patterns: A normal pattern, an isolated decrease in CD3 − , an isolated increase in TCRγδ + and coeliac lymphogram (an increase in TCRγδ + plus a decrease in CD3 − ).…”

“…However, a drawback of this meta‐analysis was the absence of a subgroup of seronegative coeliac disease among cases and a subgroup of sufficient noncoeliac atrophy patients among controls, since these are the patient subgroups for whom TCRγδ + count and coeliac lymphogram have the highest diagnostic relevance. Two of the studies included provided data on a small sample of noncoeliac villous atrophy patients suggesting that TCRγδ + count may be useful to rule out coeliac disease in this setting …”

“…10 Immunological studies assessing intraepithelial lymphocyte subpopulations by flow cytometry in fresh mucosal duodenal samples have described a coeliac intraepithelial lymphogram, defined as an increase in CD3 + T-cell receptor gamma delta + (TCRγδ + ) intraepithelial lymphocytes (IEL) plus a concomitant decrease in CD3 − cells, which seems to be highly accurate for coeliac disease diagnosis. 11,12 A recent diagnostic accuracy test meta-analysis showed that both an isolated TCRγδ + count and coeliac lymphogram are associated with a high level of diagnostic accuracy for and against coeliac disease. 13 However, a drawback of this meta-analysis was the absence of a subgroup of seronegative coeliac disease among cases and a subgroup of sufficient noncoeliac atrophy patients among controls, since these are the patient subgroups for whom TCRγδ + count and coeliac lymphogram have the highest diagnostic relevance.…”

Transglutaminase 2 and Anti Transglutaminase 2 Autoantibodies in Celiac Disease and Beyond: Anti- Transglutaminase 2 Autoantibodies: Friends or Enemies

“…Interestingly, patients with anti IgATG2 ≥ 100 U/ml show more advanced disease and carry a larger number of CD associated HLA-DQ heterodimers [18]. On the contrary, most recently, a Spanish group, found that intestinal ϒδ+ intraepithelial lymphocyte cytometric pattern is more accurate than subepithelial deposits of anti -IgA-TG2 ABs for CD diagnosis [19]. Anti TG2 autoantibodies expose a lower avidity compared with alloantibodies directed against gliadin, indicating different regulation or site of initiation of these humeral response [20].…”