Expression and Clinic Significance of PD-1/PD-L1 Costimulatory Molecules in Peripheral Blood of Rheumatoid Arthritis
|Keywords||Synergistic inhibition signal PD-1 PD-L1 Rheumatoid arthritis|
Background: Rheumatoid arthritis (rheumatoid arthritis, RA) is a synovitis, articular cartilage and bone destruction is characterized by autoimmune diseases, high morbidity, its pathogenesis has not yet been fully understood. Recent studies have found that a plurality of pairs of costimulatory molecules receptor - ligand molecule in the different periods of the immune response involved in the pathological process of autoimmune diseases, in a different manner. Programmed death ligand -1 (PD-1) belongs to a the CD28 superfamily members, programmed death receptor -1 (PD-L1) is one of the members of the B7 family, as a newly discovered negative costimulatory molecules been extensively studied in various autoimmune diseases. Therefore, the study of rheumatoid arthritis patients with peripheral blood in PD-1/PD-L1 expression characteristics, analyze its relationship with various indicators of clinical trials, and to explore the biological significance, help to elucidate the pathogenesis of RA may and provide a new therapeutic target for rheumatoid arthritis. Objective: To investigate the synergistic inhibition of the expression and clinical significance of molecular PD-1/PD-L1 in the peripheral blood of patients with rheumatoid arthritis. Methods: out-patient and in-patient hospital 56 cases of rheumatoid arthritis patients as the test group: 29 cases of active patients, 27 cases of patients in remission, the records of all patients with RA diagnostic indicators, such as rheumatoid factor (RF) anti-cyclic citrullinated peptide (CCP) antibodies, disease activity indicators such as swollen joint count, tender joint count and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and related clinical indicators, such as the patient's pain score (VAS), duration of morning stiffness, health questionnaire evaluation (HAQ), disease activity score (DAS); Another 20 cases of hospital outpatient healthy individuals as a control group. Isolated from peripheral blood mononuclear cells (PBMC) of 56 patients and 20 healthy persons, the application of flow cytometry (FCM) were used to detect PBMC on CD4 PD-1 to CD8 ~ PD-1 ~~, CD14-PD- L1 ~~, CD19 to PD-L1 to the percentage of double positive cells, and to analyze the correlation between the various related molecules and RA indicators. Results: (1) in the test group, 56 patients with RA in PBMC expression of PD-1 signal was (16.74 ± 6.67)%, significantly higher than that in the control group (13.25 ± 2.71)%, the difference was significant (P lt; 0.05). (2) in the test group, 56 patients with RA PBMC CD4 ~ PD-1 ~ cell expression was (9.80 ± 5.28)%, significantly higher than that in the control group (5.94 ± 1.41)%, the difference was statistically significant (P lt; 0.05); cells expressing both of CD14 to PD-L1 ~ rate (32.63 ± 16.08)%, (21.99 ± 6.68)%, the difference was significant resistance (P lt; 0.05). (3) in the test group, 29 patients with active RA group and 27 cases of patients with RA in remission CD4 PD-1, and CD8 to ~ PD-1, CD14 to PD-L1 ~, CD19-PD-L1 to the percentage of cells There was no significant difference between (P gt; 0.05). (4) test in peripheral blood of PD-1 expression in T cells with the RF and anti-CCP antibodies showed a significant positive correlation (r = 0.325, P lt; 0.05; r = 0.424, P lt; 0.05), with the patient's age, duration of disease, swelling joint count, duration of morning stiffness, DAS, VAS, HAQ score, ESR, CRP, were not correlated (P gt; 0.05). (5) PD-L1 expression on of CD14 ~ monocytes and CD19 ~ B lymphocytes with the patient's age, duration of disease, swelling joint count, duration of morning stiffness, DAS, VAS, HAQ, RF, anti-CCP, ESR, CRP were not related to sex (P gt; 0.05). Conclusions: PBMC from patients with rheumatoid arthritis CD4 T cells and CD14 ~ monocytes PD-1/PD-L1 molecule expression abnormally high levels, PD-1 is mainly expressed in CD4 ~ T lymphocytes, PD-L1 in CD14 ~ expression on monocytes, indicating PD-1/PD-L1 this costimulatory molecules may be involved in the pathogenesis of rheumatoid arthritis; and PD-1 expression in T lymphocytes and diagnostic indicators of the RF and anti-CCP antibodies are was a significant positive correlation with disease activity indicators such as ESR, CRP was no correlation between, suggesting that PD-1 signaling pathway may be throughout the course of RA disease always, PD-1 may be used as a diagnosis of RA immunological parameters, but can not be used to reflect the disease activity of RA.