Reduction of tissue transglutaminase autoantibody levels by gluten-free diet is associated with changes in subsets of peripheral blood lymphocytes in children with newly diagnosed coeliac disease.
Tissue transglutaminase (tTG) autoantibodies decline after gluten-free diet in patients with coeliac disease. We tested the hypothesis that gluten-free diet-induced change in tTG autoantibody levels affects subsets of peripheral blood lymphocytes. Peripheral blood was obtained from 20 children with biopsy-proven active coeliac disease. Gluten-free diet was initiated and the children examined again after three and six months. tTG autoantibodies were measured in radioligand binding assays and lymphocyte subsets by flow cytometry. IgA-tTG levels at diagnosis, 2204 U/ml (median, range 113-24990), were reduced over six months to 76 U/ml (median, range 1-1261) (P < 0.001). At six months, 12/20 (60%) children had reduced their IgA-tTG levels to < 100 U/ml and these children showed a decrease in B cells (mean change -3.8%, P = 0.014), CD4+ T cells (mean -4.32%, P = 0.011) and CD4+ T cells expressing CD25high (mean change -0.62%, P = 0.036). In contrast, the CD4+CD25(high)CCR4+ T cell population increased during the same period (mean change 11.5%, P = 0.0036). The decline in IgA-tTG levels correlated to the decrease in B cells (r = 0.56, P = 0.01), CD4+ T cells (r = 0.66, P = 0.004) as well as CD4+CD25high T cells (r = 0.59, P = 0.01). A negative correlation was found between the decline in IgA-tTG and CD4+CD25high T cells expressing CD45RO (r = -0.49, P = 0.03) and CCR4 (r = -0.54, P = 0.01). This is the first observational study on the effect of gluten-free diet on concurrent changes of tTG autoantibodies and specific peripheral blood lymphocyte subsets. Our data suggest that flow cytometry may be a useful complement to tTG autoantibodies when studying the effects of gluten-free diet in children with coeliac disease.
Unit of Diabetes and Coeliac Disease, Department of Clinical Sciences/Paediatrics, Lund University, Malmö, Sweden.
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D
Agardh
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Lynch
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Brundin
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Ivarsson
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Lernmark
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Cilio
D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018753:Diet, Protein-Restricted / Q000379:methods*; D005260:Female; D005983:Glutens / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; C515354:CCR4 protein, human; D017252:CD3 Complex; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D005983:Glutens; D011503:Transglutaminases