| Background and 0bjective Rheumatoid arthritis(RA) is one of the systemic autoimmune disease, characterized by a variety of serum-autoantibodies and symmetrical peripheral joint erosion. The prevalence rate is about 0.5%~1%. In addition to symptoms of joint involvements, nearly 50% of patients may suffer fever, anemia, subcutaneous nodules, lymph nodes, iritis and other extra-articular manifestations, and the affected organs includ the skin, eyes, nervous system, heart and lungs, etc., with the lung being the common involved organ.Pleurisy,rheumatoid nodules,Caplan syndrome, bronchiectasis and interstitial lung disease are seen in RA patients, of which, ILD is the most common symptom. The incidence of ILD is about 1% to 40% in RA patients, and about 50% of the cases occured in the first three years of RA, with an approximate average survival period of 2.6 years. The early-diagnosis of RA with ILD easily missed for the non-typical symptoms. The exact etiology and pathogenesis of RA with ILD are unknown, and its clinical manifestations, pathology and prognosis are different from RA without ILD. The age of onset, duration, male, smoking, positive rheumatoid factor(Rheumatoid factor, RF) and history-use of immunosuppressant drug such as methotrexate and other factors are risk factor occurred of RA with ILD. Variety of inflammatory cells, cytokines and chemokines such as macrophage, neutrophils, tumor necrosis factor(TNF)-?, chemokine platelet growth factor(PDGF)-?, transforming growth factor(TGF)-?, interleukin(IL)-1?, interferon(IFN), CXCL5, CXCL58, CXCL12, CXCL13 and so on,which may play an important role in the formation of pulmonary fibrosis.There are different degrees of pulmonary inflammation in interstitial lung structure, alveolar pulmonary artery or peripheral airways and so on. The formation of pulmonary fibrosis often occured in the process of inflammation and repairment. Serum high-weight-molecular-carbohydrate antigen KL-6(Krebs von den Lungen-6, KL-6) usually expressed in type 2 alveolar-epithelial-cells,with the high levels can directly reflecting destruction and inflammation of alveolus. Anti-cyclic citrullinated antibody(ACPA) is a cyclic filaggrin polypeptide fragments, which mainly based on the Fc portion of Ig G autoantibodies.it is not only a sign antibodies of rheumatoid arthritis, and can directly stimulate cells to secrete a variety of inflammatory cytokines playing a role in pulmonary fibrosis. During clinical,we can find that serum of KL-6 or ACPA in all RA with ILD are not positive.The present study was designed to study the levels of serum KL-6 and the ACPA in RA with ILD, and the correlation between KL-6 levels, ACPA titers and scores of interstitial lung fibrosis,and to expolre the correlation between KL-6,ACPA and severity of interstitial lesions.Methods A retrospective analysis of RA with ILD was conducted,with inpatients who was enrolled in August 2015 to March 2016 coming from the First Affiliated Hospital of Zhengzhou University, division of Rheumatology. The 51 cases of RA with ILD patients in hospital and 51 cases of patients who were RA without ILD. RA was diagnosis by the 1987 ACR classification criteria for RA, and RA with ILD standard should meet the 2010 Bongartz T proposed RA mergered ILD classification criteria. Besides, the exclusion criteria are including that first,merger or previous diagnosis of other lung diseases such as lung infections, tuberculosis,chronic obstructive pulmonary disease,bronchiectasis and lung tumors,etc,and second,pneumoconiosis, caused by the inhalation of organic interstitial lung disease; and third,the presence of heart dysfunction and other connective tissue diseases. Collect and analyze the medical records of RA with ILD and simple RA patients, which including age, disease duration, sex, with or without a history of smoking, serum of white blood cells(WBC), hemoglobin(Hb), platelet(PLT), total protein(TP), white blood protein(ALB), globulin(GLB), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), rheumatoid factor(RF), ACPA titers, Total lung capacity(TLC), DLCO accounts predicted percentage(DLCO% predicted),etc,and the number of computing based on disease activity Rating DAS28(ESR), and analyze the correlation between KL-6,ACPA and scores of pulmonary fibrosis on HRCT.Results The total cases of enrolled RA of the study was 102, with a total of 40 men, accounting for 39.22%(40/102).In RA with ILD group,male people were 22, accounting for 43.14%(22/51), and mean-age were(59.76 ± 10.31) years, and duration average were(8.24 ± 6.88) years,with 18 smoking patients, accounting for 35.29%(18/51)in RA with ILD.While in RA without ILD,18 patients were male,accounting for 29.51%(18/51), and the mean-age were(57.84 ± 12.97) years, and duration average were(6.52 ± 3.52) years, with 10 smoking patients, which accounting for 19.60%(10/51). When compare RA with ILD group and RA without ILD group, there were prevalence of male patients, higher proportion of smokers, older age of disease-onset, longer disease-course, but the difference were not statistically significant(P> 0.05). In the group of RA with ILD,rheumatoid factor(IU/m L)were(489.04 ± 634.15), and DAS28(ESR) were(5.36±1.90), C-reactive protein(mg/L) were(58.60 ± 52.78), which were higher than the group of RA without ILD,with rheumatoid factor being(275.45 ± 410.34), DAS28(4.11 ± 0.97), C-reactive protein(mg/L)(39.57 ± 40.57),and the difference between the two groups were statistically significant(p <0.05). In RA with ILD group, erythrocytesedimentation-rate(mm/h)were(76.48±32.54),white-blood-cell-counts(×109/L)were(6.75±2.42),platelet-counts(×109/L) were(275.93±80.97), and in RA without ILD group,erythrocyte sedimentation rate were( 64.23 ± 30.57), white blood cells were(× 109/L)(5.89 ± 3.27), platelet-counts were(× 109/L)(257.68 ± 79.34). serum of albumin(g/L) were(39.83 ± 4.32) in RA with ILD, which was lower than albumin(g/L) being(41.22 ± 5.61) in RA without ILD, the difference between the two groups was not statistically significant(P> 0.05). The lung function of RA with ILD suggest the presence of restrictive ventilatory disorders and diffuse-ventilation-disorder. Serum concentrations of KL-6(U/m L) in RA with ILD group was(419.80 ± 322.59), and ACPA(IU / ml) was(418.24 ± 396.65), while in RA without ILD, KL-6 being(224.14 ± 152.86) and ACPC being(191.66 ± 168.72).Serum levels of KL-6 and ACPA elevated in RA with ILD group, and the difference was statistically significant(P <0.05). In the group of RA with ILD,there was positive correlation(r = 0.45, p <0.001) between serum-concentration of KL-6(U/m L) and visual scores of interstitial lung fibrosis showed in HRCT,while the correlation between concentration of ACPA(IU/m L) and visual scores were unclear(p> 0.443).Conclusions 1. When compared to RA without ILD,serum levels of Kl-6 in RA with ILD significantly were higher, and there was a positive correlation between KL-6 levels and the severity of interstitial lung lesions, and the elavated levels may reflect the increased severity of interstitial lung lesions. 2. When compared to RA without ILD,serum-levels of APCA were higher in RA with ILD,and the significant correlation between its concentration and the severity of interstitial lung lesions were unclear. |
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