Cytokine Expression Pattern Of Different Types Lupus Erythematosus And Their Clinical Relevance

Objective LE(lupus erythematosus) is a chronic, autoimmune disease. Skin involvement occurs in 70–85% of all patients with LE.According to the different clinical manifestation and laboratory examination indexes, LE can be classified as SLE erythematosus(systemic lupus erythematosus lupus) and CLE(cutaneous lupus erythematosus). Abnormal immune cellular and humoral responses play important roles in the development of the disease process, various factors induced the formation of the autoimmune inflammatory reaction, eventually lead to organ damage. The pathogenesis of CLE is multifactorial and incompletely understood. It involves UV(ultraviolet) light, keratinocyte apoptosis, cytokine release, B cell hyperactivity, and activation of T cells and dendritic cells. Cytokines and autoantibody directly or indirectly act on the target tissue and ultimately lead to injury.These cytokines all assume pivotal functions to orchestrate the differentiation, maturation and activation of various cell types, which would mediate local inflammatory process and tissue injury and play an important role in the pathogenesis of SLE and CLE. Their roles may be different in the various LE subtypes. In addition to the B cells, T cells and neutrophils, Mo/Mφ(monocytes/macrophages) is also an important source of a variety of cytokines, Numerous studies have improved our understanding of the diverse components of immune dysregulation in LE, however, the pathophysiologic role of Mo/M φ remains unclear. The knowledge on these cytokines not only fosters our understanding of difference between subtypes of LE, but also provides insights in devising biomarkers and targeted therapies. Therefore, the expression model of cytokines in different types of lupus erythematosus need to be evaluated, so that some relevance between the pathogenic cytokines and clinical indicators couled be find.Method A total of 96 patients with LE(15 patients with DLE, 34 patients with SCLE and 47 patients with SLE) and 24 healthy controls were studied. The clinical characteristics of all the patients were collected in a chart review. Serum from patients with lupus was detected using protein array which contain 20 cytokines from different types of immune cells such as B cell,T cell, Mo/Mφ,etc. The significant elevation cytokines were next validated using ELISA. The interaction between cytokines were analyzed by STRING(Search Tool for the Retrieval of Interacting Genes/Proteins). Using SPSS 17.0 to compare the differences of cytokine expression patterns between the four groups, and analysis the relevance between meaningful cytokines and common clinical indicators.Results1.We find there’s extremely significant correlation between the results from protein array and ELISA:IL18(R=0.702,p=0.000), MIF(R=0.522,p=0.000), MIP1α(R=0.824,p=0.000).2.Different clinical types of LE with different cytokines expression patterns. When compared with normal controls, The cytokine expression patterns of different types LE respectively as follows: for DLE patients, IL-18(p=0.005), MIF(p=0.000), IL-17(p=0.000) were significantly elevated, for SCLE patients, IL-6(p=0.004), IL-10(p=0.000),IL-18(p=0.000),MIF(p=0.000), IL-17(p=0.000), IL-23p19(p=0.001), TNF-a(p=0.006) were significantly elevated, for SLE patients, IL-6(p=0.006),IL-10(p=0.000),IL-18(p=0.000),IL-17(p=0.000),TNFα(p=0.006),MIF(p=0.000),MIP-1α(p=0.000), IL-23p19(0.000),IFN-γ(p=0.003), MDC(p=0.008),IFN-α(p=0.020) were significantly elevated.3.The differences of the inflammatory factors level between SLE, SCLE and DLE are significant, the inflammatory factors including IL-6(p=0.047), IL-18(p=0.002), MIF(p=0.002), MIP-1α(p=0.026).4.The level of IL-17 in SLE and SCLE are significantly higher than DLE, indicating that IL-17 participated in the inflammation of SLE, SCLE and DLE, and there is a speculation that IL-17 could be an potential marker for classification of CLE and Th17 cells could have an promoting effect on the transformation of DLE and SLE.5.The significant differences of Mo/Mφrelated cytokines level between DLE, SCLE, SLE have been validated by ELISA: MIF(p=0.001), IL18(p=0.005), MIP1-a(p=0.005),and SLE patients with higher level than the others. While there is no significant difference of MIF(p=0.001), IL18(p=0.005) between DLE and SCLE.6.We find that: compared with untreated SLE patients, IL-18 and MIF significantly decreased in the patients who have been treated with corticosteroids more than 3months(P≤0.05). In addition, SLE patients who with a larger amount of protein in the urine have a higher level of IL-18 in the serum(P<0.01).What’s more, the higher the titer of ANA or the score of SLEDAI, the higher level of IL-18 in the serum(P<0.05).And analysis of correlation find that there are significantly negative correlation between the level of IL-18 and the dose of corticosteroids been treated or the amount of C3 in the serum of SLE patients, the test value respectively is r=-0.375,p=0.024 and r=-0.465,p=0.002.Conclusion This study found that different types of LE with different cytokines expression patterns, degrees of the inflammatory response were gradually increased in accordance with the order of the DLE, SCLE, SLE. Among the 20 cytokines we detected, IL-6,IL-18,MIF,MIP-1αplay an important part in the pathogenesis of LE. IL-18,MIF simultaneously participated in the disease process of DLE, SCLE and SLE, while MIP-1αwas related with the pathogenesis of SLE solely. IL-17 participated in the inflammation of SLE, SCLE and DLE, and we speculate that IL-17 could be an potential marker for classification of CLE. The dose of corticosteroids was significantly correlated with the level of IL-18,thus we think that might be a novel marker of evaluation of the effect of corticosteroid therapy. Most of the significant cytokines are derived from the active macrophages, so that the active macrophages may play a more important part in the the pathogenesis of LE than the other immune cells such as B/T cells.