ABSTRACT
Objective:To investigate the possibility of establishing a new animal model of pulmonary arterial hypertension by immunizing rat with moesin, detecting the anti-moesin antibody and measuring the mean pulmonary arterial pressure ( mPAP ) . Methods:35 male SD rats were divided into 5 groups, namely, positive control group, blank control group, adjuvant control group, low-dose moesin(250 μg per time) immunized group and high-dose moesin(500 μg per time) immunized group.Each control group had 5 rats, while the 2 immunized groups had 10 rats respectively.The mPAP was measured and the pathological changes of the lung were studied at the endpoint of the study.Results:All the rats immunized by moesin produced anti-moesin antibody.At the endpoint, low-dose and high-dose immunized group had a significantly higher mPAP(20.6±2.9 mmHg, 20.7±2.3 mmHg, respectively) than blank control(15.5 ±0.6 mmHg, P=0.002, 0.001, respectively) and adjuvant control (17.2 ±1.6mmHg, P=0.03, 0.013, respectively).There was no difference between adjuvant and blank control(P=0.93).The mPAP of both immunized groups was not as high as the positive control(33.9±4.7 mmHg,P<0.001,P=0.001, respectively).Pathological study indicated that the immunized rats showed arterial wall thickening and muscularization, as well as inflammation around the vessel, which was similar to the positive control.Conclusion:Our pilot study showed moesin could induce rat to develop PAH.Moesin immunized rat could be a new animal model, which could mimic better the pathogenesis of connective tissue disease associated pulmonary arterial hypertension.
ABSTRACT
Objective To identify a novel auto-antibody in sera of systemic sclerosis (SSc) patients and to analyze its relevance with SSc-associated interstitial lung disease (ILD). Methods The anti-moesin antibody in the sera of 62 SSc patients, who had participated the European League Against Rheumatism's Scl eroderma Trial and Research Group (EUSTAR), were tested by enzyme linked immunosorbent assay (ELJSA). Patients were grouped by high resolution computerized tomography (HRCT) features, pulmonary function test (PFT) abnormalities, inflammatory markers and disease course. The prevalence and titer (Optical density value) of anti-moesin antibody were compared between groups with t and χ2 test. Results The titer of anti-moesin antibody was significantly higher in the SSc-ILD group than non-ILD group (0.156±0.062 vs 0.107± 0.026, P=0.005). Among SSc patients, the diagnostic sensitivity and specificity of the anti-moesin antibody for ILD was 44.0% and 91.7% respectively (Kappa=0.2, P=0.022). Anti-rnoesin antibody was more prevalent in SSc patients with HRCT features of honeycomb-like lesion, lobular septal thickening and mediastinal lymphadenopathy (P<0.05). SSc patients with deteriorated total lung volume (TLC %) had higher titer of anti-moesin antibody significantly (0.172±0.067 vs 0.133±0.039, P=0.011), as the same tendency in patients with decreased diffusing capacity of the lung for carbon monoxide (DLco% ) but without statistical significant difference (0.153±0.580 vs 0.120±0.340, P=0.089). The anti-moesin antibody was equally prevalent between abnormal ESR, C reactive protein, immunoglobulin and complements groups and their normal controls (P> 0.05). Group of patients who had SSc courses more than or less than 5 years demonstrated similar anti-moesin antibody titers (0.146±0.047 vs 0.164±0.077, P=0.272). However, patients with ILD courses less than 12 months had higher liter of the antibody than controls (0.182±0.073 vs 0.138±0.049, P=0.040). Conclusion This study suggests that the novel anti-moesin antibody has comparatively high specificity for SSc-associated ILD patients, which may contribute to further understanding the pathogenesis of ILD in SSc patients. Further investigations are deserved to evaluate the application of anti-moesin antibody in facilitating early screening and evaluation of ILD.