Imaging Activated-T-Lymphocytes in the Salivary Glands of Patients with Sjögren's Syndrome by 99mTc-Interleukin-2: Diagnostic and Therapeutic Implications

Abstract

Background: Sjögren’s syndrome (SS) is a progressive autoimmune disease characterized by local mononuclear cell infiltration of the salivary and lachrymal glands. Labial biopsy demonstrates local infiltration by Th1 cells that produce pro-inflammatory cytokines, such as interleukin-2 (IL2). The aim of this study was to assess the utility of 99mTc-labelled-IL2 (99mTc-IL2) in evaluating in vivo the extent and severity of lympho-mononuclear cell infiltration in the salivary glands of patients with SS. Methods: We investigated 48 patients with primary SS and 27 control subjects using 99mTc-IL2 scintigraphy. Furthermore, in a subgroup of 30 patients, we also performed 99mTc-pertechnetate scintigraphy (99mTcO4−) for evaluation of the salivary gland function. Results: 99mTc-IL2 uptake in the salivary glands of SS patients was higher than in the control subjects (1.30 ± 0.16 vs. 0.83 ± 0.08 for parotids and 1.36 ± 0.15 vs. 1.16 ± 0.07 for submandibular glands; p < 0.0001). The salivary gland uptake of 99mTc-IL2 in patients with a longer history of disease was lower compared with the recently diagnosed patients. A significant direct correlation was found between the uptake of 99mTc-IL2 and histology. Conclusions: 99mTc-IL2 scintigraphy showed that the degree of lymphocytic infiltration of major salivary glands is variable in patients with different disease durations. Patients with a high 99mTc-IL2 uptake could be efficiently treated with immuno-modulatory drugs and the efficacy of treatment could be followed-up by 99mTc-IL2 scintigraphy.

Keywords: 99mTc-interleukin-2; Sjögren’s syndrome; activated lymphocytes; inflammation imaging; salivary glands.

Figure 1

Planar image of the neck obtained 1h after ^99mTc-IL2 injection in a control subject (A) and in a patient with Sjögren syndrome at time of diagnosis (B). In (A) the scan shows no ^99mTc-IL2 uptake by the salivary glands. In (B) an evident accumulation of ^99mTc-IL2 can be observed in both parotids and submandibular glands, indicating the presence of activated lymphocytes. The calculated parotid to background (P/B) ratios are 1.35 and 1.30 in right and left glands, respectively, and the submandibular gland to background (S/B) ratios are 1.57 and 1.64 in right and left glands, respectively.

Figure 2

Dynamic study with ^99mTcO₄⁻ in patients with Sjögren syndrome 3 years after diagnosis. (A,B) show the start of dynamic images and the summary of all dynamic images, respectively. (C,D) show the quantitative analysis of the parotid and submandibular glands, respectively. A moderate accumulation of ^99mTcO₄⁻ can be observed in the parotids and, to a lesser extent, in the submandibular glands, indicating the presence of a residual function.

Figure 3

Parotid gland uptake of ^99mTc-IL2 in patients with Sjögren disease compared to control subjects (p < 0.001).

Figure 4

Submandibular gland uptake of ^99mTc-IL2 in patients with Sjögren disease compared to control subjects (p < 0.001).

Figure 5

Distribution of the mean ^99mTc-IL2 uptake (P/B) in the parotid glands (A) and (S/B) in the submandibular glands (B) over the disease duration. A significant inverse correlation can be observed in all glands (correlation coefficient is −0.22 (p = 0.03) for the parotids and −0.29 (p = 0.006) for the submandibular glands).

Figure 6

Distribution of the mean ^99mTc-IL2 uptake (P/B) in the parotid glands (A) and (S/B) in the submandibular glands (B) over the biopsy score. A significant correlation can be observed in all glands (correlation coefficient is 0.46 (p = 0.001) for the parotids and 0.60 (p < 0.0001) for the submandibular glands).