Higher CD4+CD40+ T cells (Th40 cells) are associated with systemic lupus erythematosus activity

Studies have shown that non-autoimmune human subjects maintain peripheral levels of Th40 cells up to 30% of CD4⁺ T cell compartment^ten,14. Similar to an animal model of T1D, human subjects with T1D^ten and multiple sclerosis (MS)¹⁴ have an expansion of Th40 cells (up to 50% or more of CD4⁺ T cell compartment) in peripheral blood compared to controls. Subjects with T2DM, a chronic non-autoimmune disease, do not show this expansion^12,15,16. Expansion of Th40 cells is more predictive of T1D than the HLA-DR haplotype, and these cells are highly sensitive to T1D autoantigens¹². The same is true for Th40 cells in MS¹⁵. Th40 cells are pathogenic in T1D, EAE and MS but have not been evaluated in SLE.

In this study, we for the first time investigated the percentage of Th40 cells in Chinese patients with SLE. We demonstrated that Th40 cells in T cells from SLE patients with pathological activity are significantly higher than in healthy individuals. The percentage of Th40 cells in this study was lower than in other studies^12,15, which is probably due to the different races and species. We further investigated the role of Th40 cells in Chinese patients with SLE. The results demonstrated that Th40 cells in blood T cells from SLE patients with disease activity were significantly higher than those from healthy individuals. The percentage of Th40 cells was positively associated with SLEDAI-2000, and this was much higher if a patient with SLE had more than one organ involved. We found that higher SLEDAI-2000 scores resulted in higher percentages of Th40 cells. Thus, the percentage of Th40 cells was relative to SLE disease activity. We also found that the percentage of Th40 cells was negatively associated with C3 complement, and it is well known that C3 complement is negatively associated with SLE disease activity. This finding further confirms that the percentage of Th40 cells is positively associated with SLE disease activity. Therefore, Th40 can be used as an indicator to assess SLE disease activity. Moreover, we found that the percentage of Th40 cells in SLE patients with lupus serositis or lupus pneumonia was significantly higher than in patients without serositis or pneumonia. However, in this study, we could not test all types of SLE patients with different organs involved. Further research involving more samples and different organ involvement is needed to determine representative results. All patients with SLE accepted treatment with glucocorticoids, hydroxychloroquine and cyclophosphamide. We found that the percentage of Th40 cells of patients with SLE at the time of initial diagnosis decreased significantly after 4 weeks of treatment. SLEDAI-2000 also decreased significantly after 4 weeks of treatment and complement C3 was significantly elevated. Th40 cells (%) decreased significantly when SLE patients achieved remission or low disease activity after 1 month. Therefore, the percentage of Th40 cells can be used as an indicator to assess the effectiveness of disease treatment. Currently, few indicators are available to assess the severity of SLE. This study further demonstrated that the percentage of Th40 cells is associated with disease activity in SLE. It may be that the combination of Th40 cell percentage, SLEDAI-2000 and C3 complement can help predict SLE disease activity, distinguish its severity and predict treatment efficacy. We analyzed the levels of serum cytokines IL-2, IL-4, IL-6, IL-10, IFN-r and TNF-α in SLE. IL-6 is thought to play an important role in regulating the human immune system and plays an important role in autoimmune diseases¹⁷. However, the percentage of Th40 cells was not related to IL-6 and other cytokines. Further research involving more samples is needed to determine representative results. Th1/Th2-related cytokines include IL-2, IL-4, IL-6, IL-10, IFN-r and TNF-α. However, the percentage of Th40 cells was not related to these cytokines. Further research involving more samples, in vitro cell culture experiments, animal experiments are needed to determine representative results.

In conclusion, the percentage of Th40 cells was significantly positively correlated with SLEDAI-2000 and inversely correlated with C3 levels. Perhaps Th40 cells can be used as a predictor of disease activity, severity, and treatment efficacy. However, further research involving more samples is needed. It will be important to better understand the events leading to disease onset and to elucidate the contributions of Th40 cells.