Abnormal expression and function of Fas ligand of lacrimal glands and peripheral blood in Sjögren's syndrome patients with enlarged exocrine glands

Abstract

The objective of our study was to investigate the possibility of Fas ligand protein abnormalities in certain types of Sjögren's syndrome patients with enlarged exocrine glands. Fas ligand expression by lymphocytes infiltrating the lacrimal glands and by peripheral blood monocytes in Sjögren's syndrome patients with enlarged exocrine glands was assessed immunohistologically and by immunoblotting. Cytotoxicity of peripheral blood monocytes and sensitivity to steroids in Sjögren's syndrome patients with enlarged exocrine glands were studied by functional assay. Minimal Fas ligand expression was detected in the lymphocytes of the lacrimal glands and a decreased level of Fas ligand was found in peripheral blood monocytes as assessed by immunoblotting. Functional assay confirmed the decreased cytotoxicity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands, and that it is not affected by anti-Fas ligand antibody. By contrast, the sensitivity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands to steroids was increased. These observations suggest that abnormal expression and function of Fas ligand occurs in Sjögren's syndrome patients with enlarged exocrine glands.

Fig. 1

Immunoblotting of FasL in peripheral blood mononuclear cells (PBMC) of SS patients with EEG and SS patients. Detection of FasL in PBMCs of SS patients with EEG and SS patients. FasL is detected clearly in SS, and two bands are seen. However, only one band is present in two of the SS patients (MF and NT) with EEG, but no bands were evident in one of the SS patients (KT) with EEG. The results of quantitative analysis of immunoblotting for FasL in PBMCs of SS and SS patients with EEG by densitometry are shown as black bars. Each value represents the mean ± s.e.m. of three experiments.

Fig. 2

Functional analysis of the killing ability of PBMCs in normal controls and SS patients with EEG. FasL activity as determined by specific lysis of different effector cells: target cell ratios (E:T) of lymphocytes to Jurkat cells. PBMCs from SS patients with EEG and normal controls were stimulated with PHA for 48 h. Cytotoxicity in the SS patient with EEG was unaffected by the addition of anti-FasL antibody, whereas the normal control showed decrease of killing ability with anti-FasL antibody. Each value represents the mean ± s.e.m. of three experiments. •, Normal; ○, normal (anti-FasL); ▪, SS w/EEG; □, SS w/EEG (anti-FasL).

Fig. 3

The increased steroid sensitivity of lymphocytes in SS patients with EEG. LDH activity indicated the increased sensitivity of lymphocytes in SS patients with EEG compared to controls. Each value represents the mean ± s.e.m. of three experiments.