In this study, the average age of onset of SLE-ILD patients was 43.19±12.07 years old, while the average age of onset of SLE-NILD patients was 36.51±13.08 years old. The difference in age of onset between the two groups is statistically significant (P<0.001). SLE-ILD on average occurs about 7 years after the diagnosis of SLE is established, which is consistent with the results of earlier studies. Toyoda et al. [8] retrospectively analyzed 69 SLE patients and found that SLE-ILD accounted for 29%, of which 70% were women. The average age of diagnosis of SLE-ILD in this study was 53.4 years old, which was significantly higher than the SLE-NILD in the study (38 years old), P = 0.003. Boddaert et al. [9] analyzed 714 late-onset SLE cases (diagnosed after the age of 50) and 47 early-onset cases and found that the incidence of ILD increased with age: early-onset cases 11.3% vs. late-onset cases 21.2%. Cervera et al. [10] reported that 3% of patients with ILD were diagnosed at the same time with SLE, and 7% of patients gradually developed ILD during the course of SLE. The study of Boddaert et al. [9] found that the age-related gender ratio decreased: female: male = 4.4:1 in late-onset patients vs. female: male = 10.6:1 in early-onset patients. In our study, there is no difference in gender and smoking history between the two groups (P>0.05), and they are more common in women and non-smokers.
There is no conclusion about the correlation between autoantibodies in SLE patients and ILD. Studies have shown that in autoimmune diseases, patients with ILD have a higher ANA positive rate than patients without ILD [11]. Our study found that there was a significant difference in the positive rate of ANA between the SLE-ILD group and the SLE-NILD group. That is, SLE-ILD patients have a higher ANA positive rate than SLE-NILD patients, and ANA can be recommended as a screening index for the onset of SLE-ILD. Lin Bing et al. [12] pointed out in a study of 100 SLE-ILD patients that compared with SLE-NILD patients, SLE-ILD patients had lower levels of anti-dsDNA antibody known as a lupus specific serum marker. While Hedgpeth M T [13] meaned that the severity of ILD was not affected by anti-dsDNA antibody, and was less affected by anti-SS-A antibody. Anti-Sm antibody is the hallmark antibody of SLE. Studies [14] have shown that anti-Sm antibody was related to ILD. Lian et al. [15] found that anti-SS-A antibody, anti-SS-B antibody, and anti-SCL70 antibody were all related to SLE-ILD through multiple regression analysis. However, our study only found a significant difference in the positive rate of ANA between the two groups, while the other 13 autoantibodies studied were not significantly different. Data from a large random trial are needed to further verify whether each autoantibody is compatible with SLE-ILD and to clarify the mechanism of each correlation at cellular and molecular levels.
In the study, the common clinical symptoms of SLE-ILD patients were fever, cough, sputum, chest tightness, dry cough, and shortness of breath. However, progressive dyspnea after activities was relatively rare. We consider the above atypical symptoms of interstitial lung damage ( Such as fever, cough and sputum) are mostly related to the long-term use of glucocorticoids, immunosuppressive drugs and other drugs after the diagnosis of SLE, which leads to the immune dysfunction and is likely to cause secondary infections.
The most common abnormal pulmonary auscultation sign in the SLE-ILD group was pulmonary rales. 76.92% of these patients had Velcro rales, typical of interstitial pneumonia. 75.28% of patients did not find positive pulmonary signs, suggesting that only relying on lung auscultation signs as the diagnostic basis for SLE with ILD may cause false negative and reduce the detection rate.
Lian et al. [15] reported that ground glass density shadow was the most common imaging change in SLE-ILD patients, accounting for about 84.4% and the remaining imaging changes are nodular shadows (21.1%), honeycomb shadows (15.6%) and traction bronchiectasis (12.8%). In this study, the common lung imaging abnormalities in SLE-ILD patients were grid-like shadows (48.31%), ground glass density shadows (46.07%), and interlobular thickening (17.98%). The lesions involving both lungs account for 84.27%. But SLE patients did not routinely undergo HRCT examination, the above mentioned data may be lower than the actual. In clinical work, we should not only pay attention to the typical imaging manifestations of interstitial pneumonia, but also not ignore some relatively rare abnormal manifestations such as subpleural line shadows, cellular changes, traction bronchiectasis, etc., especially cellular changes which often represent severe pulmonary fibrosis difficult to reverse. Previously report said that the most frequently observed change on HRCT in SLE-ILD patients was NSIP. Toyoda et al. [16] retrospectively analyzed 69 SLE patients, UIP accounting for 25% and NSIP accounting for 55% on HRCT. Long-term imaging follow-up showed that most patients' disease progressed slowly, and most of the lung function indexes could be maintained, and there was no significant difference in survival rate between ILD and NILD patients.
The abnormalities of pulmonary function in SLE-ILD patients were mainly restrictive ventilatory dysfunction and impaired diffusion function. Two independent sample t-tests found that the abnormal changes in pulmonary function in SLE-ILD patients were not affected by smoking history. That is, the effect of smoke on lung interstitial changes is far less than the effect of immune damage.
However, this study did not find a correlation between pulmonary function indexes (including ventilation function and diffusion function indexes) and autoantibodies in SLE-ILD patients. Considering the included study samples were only 28 cases, there may be selection bias affecting the analysis results. The receiver operating curve analysis found that ANA and Ro-52 were meaningful for the diagnosis of SLE-ILD. The diagnostic sensitivity of ANA is high to 97.8%, but the specificity is very low, only 3.2%. The diagnostic sensitivity of Ro-52 is 61.8%, specificity 52.9%. The results indicate that ANA and Ro-52 have a suggestive effect on the possibility of SLE-ILD, but differential diagnosis is still needed. Further binary Logistic regression analysis found that age, ANA, SM, and Ro-52 were independent risk factors for the onset of SLE-ILD. The above can provide certain guidance and decision-making significance for patients with clinically suspected SLE-ILD.
At present, there are few studies on the relationship between autoantibodies and SLE-ILD. In this study, the chi-square test of autoantibodies in SLE-ILD and SLE-NILD patients, the correlation analysis of pulmonary function indicators and autoantibodies in SLE-ILD patients, the receiver operating curve analysis of autoantibodies for the diagnosis of SLE-ILD and the binary Logistic regression analysis between autoantibodies and other factors and the onset of SLE-ILD reveal the value of some autoantibodies for the diagnosis and prognosis of SLE-ILD, which will definitely contribute to clinical work. However, due to the retrospective nature of this study, the implementation of HRCT and the acquisition of pulmonary function data have a strong passivity, it is impossible to further analyze and stratify the imaging data and pulmonary function, which affects subsequent statistics result and its accuracy.