CD1 Molecules Expression In Peripheral Monocytes And Lymphocytes In Juvenile Diabetic Patients

BackgroundType 1 diabetes may be caused by destruction of homeostatic balance of the immune system, while the etiology remains poorly understood. This disease is thought to be mediated by pathogenic T cells specific for pancreaticβcells. The discovery of lipid antigen presentation pathway may provide a new perspective for the pathogenesis of diabetes. As a molecule recognizing lipid antigen, CD1 molecules have a broad distribution on the surface of lymphocytes and monocytes. After recognition of foreign or self lipid antigens, CD proteins can bind specific receptors on the surface of CD1-restricted cells. CD1 molecules may play a crucial role in various autoimmune diseases, such as autoimmune thyroid diseases and systemic lupus erythematosus. The mechanism of the CD1 molecules in autoimmune diabetes is still unknown, especially for the group 1 CD1 molecules. In our study we detected CD1 isoforms expression in monocytes and lymphocyte of peripheral blood by flow cytometry in juvenile diabetic patients under the age of 25 with the duration of diabetes less than 6 months and healthy controls, to find out the difference in positive expression between patients and controls. Then we explored the relation of the positive expression of CD1 isoforms on the surface of monocyes and lymphocytes with BMI, HbAlc, duration, age and thyroid function. Investigation of the expression of CD1 isoforms expression may suggest a possible effector role in autoimmune diabetes. Method1. The study was carried out in department of Endocrinology in Nanjing Gerneral Hospital of Nanjing Military Command from March 2010 to January 2011.31 subjected with diabetes included 18 boys and 13 girls aged between 3 to 25 years old and duration of diabetes was less than 6 months. The exclusive criteria were as follows:BMI>30 Kg/m2; acute and chronic disorders of liver and kidney; combined with another endocrinology disease. The control group included 23 healthy blood dornors aged 20 to 25. Periphery blood was obtained by venepuncture from patients and healthy controls subjects.2. All the patients and controls were detected for the positive expression of CD1 isoforms on the surface of monocytes and lymphocytes. All the subjects were physically examined and detected for HbAlc, anti-islet autoantibodies, blood lipid, thyroid function, and the body mass index (BMI) were determined.3. The positive expression of CD1 isoforms in diabetes patients was compared with that of in controls. The relation of positive expression of CD1 isoforms with HbAlc, duration, age, and thyroid function was explored.Results1. Comparison of group 1 CD1 molecules Surface expression of CD1a and CD1c in monocytes in patients was more than that of in controls (P<0.05), while CDlb expression in those cells did not show significant difference between patients and controls (P>0.05). On the surface of lymphocytes CD1a and CD1c expression was higher than controls (P<0.05), and CDlb expression did not show great difference (P>0.05).2. Comparison of group 2 CD1 molecules The expression of CD1d on the surface of monocytes did not show great difference in patients, compared with that of in controls (P>0.05), while on the surface of lymphocytes CDld expression was higher than controls (P<0.05).3. Relation of CD1 isoforms expression with duration, BMI and age in patients CD1a and CD1c expression in monocytes and lymphocytes showed to be increased with duration in patients (P<0.05), and correlation between other CD1 isforms and duration was not found (P>0.05). CD1 isoforms expression in monocytes and lymphocytes showed no relation to BMI and age (P>0.05).4. Relation of CD1 isoforms expression with HbA1c in patients Correlation between CD1 isforms and HbA1c was not found in patients (P>0.05).5. Relation of CD1 isoforms expression with thyroid function in patients CD1d expression on the surface of monocytes was positively associated with FT4 levels (P<0.05). CDla expression on the surface of lymphocytes was positively related to FT4 levels (P<0.05). CD1c expression on the surface of lymphocytes showed to be increased with TSH levels (P0<.05). Correlation between other CD1 isoforms and thyroid function was not found on the surface of monocytes or lymphocytes (P>0.05).Conclusions1. CD1a and CD1c expression in monocytes and lymphocytes might associate with development of diabetes in juvenile patients. These observations give rise to a hypothesis about the pathogenesis of human autoimmune disease that diabetogenic T cells recognize self-lipid antigen ofβ3 cells, leading to destruction ofβcells. But the enhanced immune cells recognition of foreign or self lipid antigen due to microbe infection may also play a role.2. The increased CD1a expression on the surface of monocytes and lymphocytes with the development of diabetes in patients suggests disease progression induce exposure of lipid antigen.3. Some CD1 isoforms on surface of monocytes and lymphocytes positively associate with thyroid function. Recognition and attack target cells in thyroid tissues may involve lipid antigen presentation in juvenile diabetic patients.