In recent years, some studies have focused on new mechanisms affecting the innate and acquired immune systems in different stages of systemic lupus erythematosus. Cytokines play an important role in the pathogenesis of inflammation regulation and affect the severity of autoimmune diseases. Further analysis showed that thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine, which has been extensively studied in atopic and rheumatic diseases.The landscape of therapeutic agents that can modulate the bioactivity of TSLP and IL-7 ininflammation, autoimmunity and cancer is clearly very broad in terms of disease coverage and displays a strong focus on biologics. Considering the important role of both TSLP and IL-7 in the pathogenesis of RA simultaneous inhibition of both TSLP and IL-7R signaling in arthritis could serve aplausible the rapeutic rationale in arthritis.
Multiple studies have also shown that in human cells and animal models of Rheumatoid arthritis (RA) and Lupus nephritis (LN), overexpression of TSLP can induce T cell activation and pro-inflammatory cytokine production. Therefore, TSLP-IL17-a receptor axis has great potential for targeted therapy. Another important feature of TSLP is its ability to act as an initiator of allergic inflammation in both human and mouse[24, 25]. Elevated TSLP levels are found in affected skin and lung from patients of a topic dermatitis or allergic asthma,respectively. Consistent with this ,mice overexpressing TSLP or administered with recombinant TSLP exhibit severe Th2-polarlized inflammation in the sites.
However, as far as we know, there is no research report on TSLP and SLE. Here, we provide the first evidence that TSLP can be used as a biomarker for predicting SLE disease activity and monitoring treatment. In this study, we found that patients with systemic lupus erythematosus (SLE), regardless of the stable group, the active group, the lupus nephritis group, and the lupus-related interstitial lung disease group, had significantly higher serum TSLP levels than the healthy control group. It suggests that TSLP may be involved in the pathological process of systemic lupus erythematosus host immune response and provides a new perspective for identifying the disease activity of systemic lupus erythematosus. More importantly, our research results show that according to the SLEDAI-2K score, the TSLP level of patients with moderate and high activity SLE is significantly higher than that of patients with low activity SLE, indicating that the high activity of SLE has higher sensitivity and specificity. Therefore, TSLP can be used as a new and sensitive biomarker for SLE with moderate to high disease activity.
Significantly, lupus nephritis and interstitial lung disease are common comorbidities in patients with SLE, and the higher the cumulative disease activity, the higher the risk of comorbidities[32–34]. In our study, we found that the serum TSLP level of the SLE-ILD group was significantly higher than that of the SLE group without comorbidities. This means that high TSLP levels may be related to the severity of the disease, thereby predicting the poor prognosis of active SLE.
Certain biomarkers are more valuable than diagnostics in guiding treatment and prognosis. For example, several biomarkers such as TNF-α, IL-6, IL-33 and MMP-3 are used to evaluate the effect of clinical treatment[35–38]. Our current results show that after effective comprehensive treatment, the serum level of TSLP may decrease significantly. In addition, we also focused on the changes in clinical characteristics of SLE patients with moderate and high disease activity before and after treatment and their correlation with TSLP levels. Therefore, TSLP may become a potential marker for monitoring clinical efficacy.
However, some limitations of our research should be considered. On the one hand, there are relatively few samples of lupus-related interstitial lung disease, which need to be further verified in the expanded sample; on the other hand, the number of cases in the biologics treatment group is too small to represent the expression level of TSLP. In our study, most patients have long-term SLE, and disease activity is assessed at the time of admission, which may not represent all chronic inflammation in the entire course of the disease. In the future, a multicenter study based on long-term follow-up is still needed to further evaluate the patient's condition at the time of onset.
In summary, our research results indicate that TSLP may become a new sensitive biomarker for predicting the disease activity of SLE patients and monitoring the effect of treatment, helping to identify patients with higher activity early and to adjust treatment options timely. Therefore, this study provides new ideas for the study of SLE disease activity, but the potential immunopathological role of TSLP in SLE autoimmunity remains to be further studied.