The Levels Of MMP-9,TIMP-1,TGF-β1 In Serum And Bronchoalveolar Lavage Fluid In Rheumatoid Arthritis Patients With Interstitial Lung Disease And Their Clinic Significances

OBJECTIVESRheumatoid arthritis (RA) is an autoimmune disease that mainly characterized by chronicinflammation of joints and the tissue around joints. Interstitial lung disease (ILD) is thecommon seen complication of it. This study aims to explore the clinical significance ofMatrix metalloproteinases (MMPs), The inhibitor of matrix metalloprotenases (TIMPs)and Transforming growth factor-β(TGF-β) by detecting them in the serum and alveolarlavage liquid of patients with RA and ILD.METHODSMaterials57 cases with complete clinical information and blood serum samples are collected anddivided into two groups, 29 with RA only as RA group and 28 with ILD as RA-ILD group.3 patients from RA group and 6 patients from RA-ILD group were performedbronchoalveolar lavage. Patients in RA-ILD group are divided into 2 more groupsaccording to chest CT and lung function tests, 16 in early RA-ILD group and 12 in lateRA-ILD group. 29 cases are selected from people taking physical examination in No. 1Hostpital as healthy control group. ELASA was used to detect the levels of MMP-9,TIMP-1, TGF—β1 in serum and bronchoalveolar lavage fluid of three groups, then processthe data.RESULTS1. Comparison the levels of MMP-9, TIMP-1 and TGF-β1 in serum among threegroups: TIMP-1 level of both RA-ILD and RA groups is significantly higher than that of control group(p＜0.01). The TGF-β1level of RA-ILD group is significantly higher than thecontrol group (P＜0.01) and RA group (P＜0.01). There is no difference on TIMP-1 levelbetween RA-ILD and RA groups, TGF-β1 level between control group and RA group,MMP-9 level among three groups.2. Comparison of MMP-9/TIMP-1 ratio among threegroups: The MMP-9/TIMP-1 ratio of late RA-ILD group is much lower than that of earlyRA-ILD group. There is no difference on MMP-9/TIMP-1 ratio between RA and RA-ILDgroups (p=0.116).3.Analysis of sub-groups: The TIMP-1 level in serum of late RA-ILDgroup is much higher than that of early RA-ILD group (p＜0.01). The TGF-β1 level inserum of late RA-ILD group is much higher than that of early RA-ILD group (p＜0.05).There is no statistic significance on MMP-9 level in serum between early and late RA-ILDgroups (p=0.175).4. Comparison of disease course, joint x-ray classification, PO₂, ESR,CRP, RF between RA early and late RA-ILD groups:Only the PO₂ of late RA-ILDgroup is much lower than that in early RA-ILD group (p＜0.01).5. Comparison ofMMP-9,TIMP-1,TGF-β1 and MMP-9/TIMP-1 ratio among bronehoalveolar lavagefluid of three groups: The TGF-β1 level in bronchoalveolar lavage fluid of RA-ILDgroup is much higher than that of control group and RA group (P＜0.05).6. Comparison ofcell count among bronchoalveolar lavage fluid of three groups: The white cell countand the percentage of polymorphonuclear neutrophils(PMNs) in bronchoalveolar lavagefluid of RA-ILD group is much higher than that of control and RA groups (p＜0.05). Thepercentage of macrophage in alveolar lavage fluid of RA-ILD group is much lower thanthat of control and RA groups (P＜0.05).CONCLUSION1.The TGF-β1 level of RA-ILD group is highly increased when comparing with controland RA groups. It is significantly higher in late RA-ILD group than early RA-ILD group. Itindicates that TGF-β1 can be used as a diagnostic index of ILD in RA patients and alsoreflect the pathological change of lung.2. The MMP-9/TIMP-1 ratio in late RA-ILD group is much lower than in early RA-ILDgroup while TIMP-1 is higher in late RA-ILD group than in early RA-I:D group. Itindicates that the decrease of MMP-9/TIMP-1 ratio in RA patients with ILD can reflect theseverity degree of lung pathological changes and be used to instruct therapy.3. There is no difference on MMP-9 level among RA, RA-ILD and control groups, as well as between early and late RA-ILD groups. It shows that MMP-9 can not be used as adiagnostic index of RA-ILD, either a determinant to evaluate the severity of ILD.4.The TGF—β1 level, white cell count, PMNs percentage in bronchoalveolar lavage fluidof RA-ILD group is much higher than those of both control and RA groups. However, itsmacrophage percentage is much lower than control and RA groups. It needs furtherresearch on its clinical significance since we do not have enough BAL samples.