Down-regulation of cytotoxic expression on peripheral blood mononuclear cells in patiens with primary Sjogren's syndrome

Background: The main peripheral blood mononuclear cells (PBMCs) involved in cytotoxicity are T cytotoxic lymphocytes (CD3+/CD8+), Natural Killer (NK) cells (CD3-/CD16&CD56+), NK-like T cells (CD3+/CD16C&D56+); the role for these lymphocyte subsets has been partly investigated in Sjogren's syndrome (SS) 1,2. Objectives: To detect the main cytotoxic cell subpopulations in a group of patients with primary SS, investigating their role in the determinism of the disease and their possible relationship with the main clinical and laboratory parameters. Methods: Thirty-three patients [M/F=3/30; mean age=52.8 yrs (range 26-78); mean disease duration=9.2 yrs (range 0.3-36)] with primary SS, classified according to the European criteria, were enrolled in the study. Twenty-four healthy subjects, matched for sex and age, were chosen as controls. PBMC subset analyses were performed by direct dual immunofluorescence and flow cytometry (FACSan, Becton Dickinson, Mountain View, CA). The following monoclonal antibodies were used: anti-CD3, anti-CD4, anti-CD8, anti-CD19 and anti-CD16&CD56 (specific for the NK-associated antigen). Laboratory investigations included: ESR, CPR, IgG, IgA, IgM and antinuclear, antiSSA/Ro, antiSSB/La antibodies. Results: SS patients showed a significant decrease, respect to controls, in the absolute number of total lymphocytes (p<0.009), CD3 (p<0.003), CD4 (p<0.01), CD8 (p<0.007), NK (p<0.0007), NK T (p<0.001) positive cells, as well as in the percentage of CD8 (p<0.011) NK (p<0.006), NK T (p<0.01) positive cells and in the CD4/CD8 ratio (p<0.015). The absolute number and the percentage of B cells (CD19+) were higher respect to controls (p<0.015 and p<0.00001, respectively). The total lymphocyte number positively correlated with CD8 (p<0.0001), NK (p<0.0001) and NK T (p<0.0002) positive cells. The absolute number of NK cells positively correlated with CD8 (p<0.01) and NK T (p<0.006) positive cells. Besides the absolute number of NK T cells positively correlated with CD8 subset (p<0.0008). The increase of the absolute number and percentage of B cells inversely correlated with total T lymphocyte subset (CD3+)(p<0.01 and p<0.0014, respectively). SS patients with antiSSB/La positivity had lower number of CD3+ lymphocytes (p<0.03). Conclusion: Cytotoxic cells are known to play a pivotal role in the normal function of human immune system and their activity is important in preventing autoimmune processes. Our primary SS patients were found to have an impairment of all the examined cytotoxic cell subsets. As already shown for other autoimmune diseases3,4, these data suggest that among the different immunological pathogenetic mechanisms of primary SS, those concerning cytotoxicity seem to be involved in the development of this disease1. Gonzalez-Amaro R. et al. Natural killer cell activity in the systemic connective tissue disease. J Rheumatol 1988; 15: 1223-8.2. Ichikawa Y. et al. Lymphocyte subsets of the peripheral blood in Sjogren's syndrome and Rheumatoid Arthritis. Clin Exp Rheumatol 1989; 7: 55-61.3. Riccieri V. et al. Down-regulation of natural killer cells and of γ/δ T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity? Lupus, 2000; 9: 333-7.4. Seaman WE. NK cells and NK T cells. Arthritis Rheum 2000; 43: 1204-17. 1. Gonzalez-Amaro R. et al. Natural killer cell activity in the systemic connective tissue disease. J Rheumatol 1988; 15: 1223-8.2. Ichikawa Y. et al. Lymphocyte subsets of the peripheral blood in Sjogren's syndrome and Rheumatoid Arthritis. Clin Exp Rheumatol 1989; 7: 55-61.3. Riccieri V. et al. Down-regulation of natural killer cells and of γ/δ T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity? Lupus, 2000; 9: 333-7.4. Seaman WE. NK cells and NK T cells. Arthritis Rheum 2000; 43: 1204-17.