Imaging active lymphocytic infiltration in coeliac disease with iodine-123-interleukin-2 and the response to diet

Abstract

Coeliac disease is diagnosed by the presence of specific antibodies and a jejunal biopsy showing mucosal atrophy and mononuclear cell infiltration. Mucosal cell-mediated immune response is considered the central event in the pathogenesis of coeliac disease, and untreated coeliac patients show specific features of T-cell activation in the small intestine. Here we describe the use of iodine-123-interleukin-2 scintigraphy in coeliac patients as a non-invasive tool for detection of lymphocytic infiltration in the small bowel and its use for therapy follow-up, and we demonstrate the specificity of binding of labelled-IL2 to activated lymphocytes by ex-vivo autoradiography of jejunal biopsies. 123I-IL2 was administered i.v. [74 MBq (2 mCi)], and gamma camera images were acquired after 1 h. Ten patients were studied with 123I-IL2 scintigraphy at diagnosis and seven were also investigated after 12-19 months of gluten-free diet. Results were expressed as target-to-background radioactivity ratios in six different bowel regions before and after the diet. At the time of diagnosis all patients showed a significantly higher bowel uptake of 123I-IL2 than normal subjects (P < 0.003 in all regions). A significant correlation was found between jejunal radioactivity and the number of IL2R + ve lymphocytes per millimetre of jejunal mucosa as detected by immunostaining of jejunal biopsy (r2 = 0.66; P = 0.008). Autoradiography of jejunal biopsies confirmed that labelled-IL2 only binds to activated T-lymphocytes infiltrating the gut mucosa. After 1 year of the diet, bowel uptake of 123I-IL2 significantly decreased in five out of six regions (P < 0.03), although two patients still had a positive IL2 scintigraphy in one region. We conclude that 123I-IL2 scintigraphy is a sensitive non-invasive technique for assessing in vivo the presence of activated mononuclear cells in the bowel of patients affected by coeliac disease. Unlike jejunal biopsy, this method provides information from the whole intestine and gives a non-invasive measure of the effectiveness of the gluten-free diet.

Detection of Insulitis by Pancreatic Scintigraphy With 99mTc-Labeled IL-2 and MRI in Patients With LADA (Action LADA 10)

“…Instead, radiolabeled IL-2 has optimal characteristics for in vivo detection of activated T cells in infiltrated tissues. It allowed detection of insulitis in two animal models of autoimmune diabetes, and a positive correlation between 123 I-IL-2 scintigraphic uptake and the degree of lymphocytic infiltration was observed by gamma camera imaging and proved histologically (9)(10)(11)(12)(13).…”

“…In particular, in patients with celiac disease it was possible to detect jejunal infiltration and to monitor the effect of diet on the immune process (9). Specific binding of radiolabeled IL-2 to activated lymphocytes was also clearly demonstrated by ex vivo microautoradiography and immunostaining; tissue specimens revealed that jejunal accumulation of 99m Tc-IL-2, as measured in vivo by single photon emission computerized tomography (SPECT), correlates with the number of infiltrating activated mononuclear cells per millimeter of mucosa (9). Similar results were achieved in patients with active Crohn's disease in whom 123 I-IL-2 scintigraphy was used to monitor the efficacy of therapy with corticosteroids (10).…”

99mTc-interleukin-2 scintigraphy in normal subjects and in patients with autoimmune thyroid diseases: a feasibility study

“…In vivo imaging of chronic inflammatory processes would help to overcome some of these limitations by providing direct evidence of the immune process and might contribute to the management of patients with autoimmune diseases [7,8]. 123 I-labelled IL2 ( 123 I-IL2) has been shown to detect with high accuracy lymphocytic infiltration in a series of patients with immune-mediated diseases [2,3]. Owing to, however, the cost of 123 I-IL2, only a limited number of Tc-IL2 patients can be studied; 123 I, moreover, is not readily available, and the preparation of 123 I-IL2 is a lengthy multistep procedure that requires the availability of a dedicated radiochemistry laboratory.…”

“…Previous studies with 123 I-labelled IL2 ( 123 I-IL2) in several patients with immune-mediated diseases showed specific targeting of tissues-infiltrated by activated lymphocytes; rapid clearance from the circulation through the kidneys was observed, and major organs of uptake were kidneys, liver and spleen with minimal intestinal excretion. No side effects were reported [2,3]. Radiolabelled IL2 might be a useful radiopharmaceutical in different immune-mediated diseases: it might guide the diagnosis and treatment of the disease by providing relevant information about the presence of the ongoing inflammatory process.…”

Radiopharmaceuticals for imaging chronic lymphocytic inflammation

“…Exvivo autoradiographic examinations demonstrated the specific binding of 123 I-IL2 to activated lymphocytes in the inflamed gut mucosa (Signore et al, 1999a). In another study in the patients with coeliac disease, a positive correlation was observed between the uptake of 123 I-IL-2 measured by gamma camera and the number of histologically determined IL-2 receptor-positive cells in the inflamed jejunal mucosa (Signore et al, 1999b). Similarly,99m Tc-labelled IL-2 also showed specific accumulation in the inflamed tissue in several diseases such as insulin dependent diabetes (Signore et al, 1996) and melanoma (Barone et al, 1998).…”