A Study On The Changes And Significances Of CD35, CD55 And MPO On Neutrophil And The Ba In The Peripheral Blood And Urine From Patients With MPO-ANCA Associated Vasculitis

BACKGROUND MPO-ANCA associated vasculitis(MPO-AAV) was one of the most common small vasculitis in our country, it included Microscopic polyangiitis(MPA), Granulomatosis with polyangiitis(GPA) and Eosinophilic Granulomatosis with polyangiitis(EGPA). Because of hiding onset, diversity of clinical manifestations and rapid progression of the disease, the patients often failed to be diagnosed and treated in time, which might cause death. Based on the animal experiments, in vitro experiments and clinical researches in recent years, it was found that the activation of the alternative pathway of complement might play an important role in the pathogenesis and progression of MPO-AAV. Activation of the complement system was controlled by many factors, such as CD35, CD55. It was reported that CD35 and CD55 played an important role in the regulation of complement system in some autoimmune diseases including rheumatoid arthritis(RA). But study on the relationship between CD35, CD55 and complement activation in MPO-AAV had not been reported by now.OBJECTIVE To investigate the changes of neutrophil activity, the state of alternative complement pathway activation and regulation in MPO-AAV patients, and to detect the relationship between them and the clinical damages.METHODS Forty patients with active MPO-AAV, whose blood, sera, urine and clinical data including Birmingham Vasculitis Activity Score-version 3(BVAS-V3) were collected, were involved in this study. The same samples from health were also collected as controls. The expression of CD35, CD55, MPO on neutrophil were analyzed by flow cytometry(FCM), the Ba level in sera and urine were detected by enzyme-linked immunosorbent assay(ELISA).The relationships between CD35, CD55, MPO, Ba and the clinical damages were detected.RESULTS1. Compared with the control group, the expressions of CD35, CD55 on neutrophil from the of MPO-AAV patient group was significantly higher(t=3.339, p=0.001; t=2.180, p=0.033); the expression of MPO inside the neutrophil of MPO-AAV patient group was lower(t=-3.161, p=0.003); the Ba level in sera of MPO-AAV patient group was obviously higher(Z=-4.641, p<0.001).2. The mean fluorescent intensity(MFI) of CD35 on neutrophil of MPO-AAV patient group was positively associated with Ba level in sera and urine(r=0.336, p=0.034; r=0.324, p=0.041, respectively).3. The MFI of CD35 on neutrophil of MPO-AAV patient was positively associated with the age of patients(r=0.424, p=0.006), C reactive protein(CRP)(r=0.516, p=0.001), complement C3(r=0.494, p=0.020) and peripheral white blood cell count(r=0.433, p=0.005). The MFI of CD55 on neutrophil of MPO-AAV patient was positively associated with the patients age(r=0.514, p=0.001), the total BVAS(r=0.441, p=0.004), CRP(r=0.377, p=0.020), complement C4(r=0.445, p=0.038), peripheral white blood cell count(r=0.488, p=0.001) and the pulmonary BVAS(r=0.358, p=0.023). The MFI of MPO inside the neutrophi of MPO-AAV patient was positively associated with complement C4(r=0.572, p=0.021). The Ba level in urine of MPO-AAV patient group was positively associated with erythrocyte sedimentation rate(ESR)(r=0.373, p=0.025), CRP(r=0.399, p=0.013) and the pulmonary BVAS(r=0.318, p=0.046).4. Compared with the patients without pulmonary involvement, the patients with pulmonary involvement had higher MFI of CD35 and MPO(t=-2.373, p=0.023; t=-2.121, p=0.043, respectively). Compared with the patients without kidney involvement, the patients with kidney involvement had higher MFI of CD55(t=-2.412, p=0.021).CONCLUTION1. The expression of complement activation inhibitory factors CD35 and CD55 on neutrophil of patients with MPO-AAV were significantly enhanced, which might prevent the neutrophils from being destroyed by activated complement system, thus the inflammation related to the neutrophil should be aggravated.2. The lung of MPO-AAV patient who had high expression of CD35 on neutrophils might be more susceptibe to involve. The kidney of MPO-AAV patient who had high expression of CD55 on neutrophils might be more susceptibe to involve.3. Compared with the health controls, the MFI of MPO inside the neutrophil of the patients was significantly lower, which might indicated that MPO which released during neutrophil degranulation played a more important role in the pathogenesis and progression of MPO-AAV.4. Alternative complement pathway activation increased significantly of MPO-AAV patients, but the Ba level in sera had no obvious relationship with the severity of clinical damages of MPO-AAV patients. The detection of Ba in urine could be helpful for the clinical evaluation of the disease activity.