The Role Of Complement Activation And CD4~+ Helper T Lymphocyte In Liver Damage Of Patients With Drug Eruption

Background Drug eruption is a common clinical skin drug adverse reaction,drug enters the body through different ways and as a res?lt cause skin mucous membrane disease.With the change of purchasing medicine way,non-standard ways of using drugs,leading to the incidence of drug eruption rise year by year,and drug rash type and type of sensitization drugs also showed a trend of diversification.Severe drug eruption has a high case fatality rate and bring a serious economic burden to family and society.Therefore,the research of drug eruption mechanism and how to prevention of severe drug eruption is not only an important content in clinical work,but also a public health problem that deserves attention.Studies have shown that the activation of T lymphocytes and functions play an important role in drug eruption,and the dominant role of T lymphocyte subsets in different periods also have very big difference,CD4+ T cells and CD8+ T cells and CD4+T/CD8+T all play an important role in immune reg?lation.At the same time in trichloroethylene drug eruption dermatitis,we found that in animal models the proportion of Th17 and Th1 in CD4+ T cells and Th1 / Th2 imbalance may play an important role in its pathogenesis,and complement may be involved in the reg?lation of T cell subgroup.Th22 is one of the newly discovered CD4+ T cells in recent years,mainly related in the skin mucous membrane barrier system.There are so many studies in SLE,psoriasis,atopic dermatitis and other skin diseases,but only a few research in drug eruption.Previous research studies have found that there is a significant reduction in the serum C3,suggesting drug eruption may exist a phenomenon of complement activation.Studies have found that the levels of serum C3 drops in DMLT patients,and the levels of C3 is negatively correlated with liver injury.Previous research studies also found that a significant C3 reduction in patient with drug eruption,which is consistent with trichloroethylene drug eruption sample research of dermatitis,but the C3 falling is caused by the liver damage or due to consumption of complement activation C3,we do not understand.Therefore,on the basis of the study in the early stage,we further explore the changes and the role of immune related indicators in patients with drug eruption,the reason of C3 decline and different CD4+ helper T cell subgroup in drug eruption.Objective Analysis immune related changes of different degree liver damage in patients with drug eruption,detect serum complement protein level,T cells related inflammation factors and the change of T cell subgroups of drug eruption patients,to explore its possible role in patients with drug eruption.Methods 1 Collect information and medical records of patients with drug eruption in the first affiliated hospital of anhui medical university dermatological department from September 2014 to March 2016.Analyze all the basic information(sex,age,type of drug eruption,sensitization drugs,the incubation period,hospitalization days,hospitalization expenses,liver function,immune related indicators,etc.).2 In this study,we collect 35 cases of hospitalized patients with drug eruption and matched healthy controls during the study,detect the ALT and AST,and use enzymelinked immunosorbent assay to detect the serum IL – 22 and IL-13,and adopt the method of CBA to detect the serum IFN-?,IL-4,IL-2,IL – 17,IL-6,IL-10,TNF-?,use the FCAP Array and SPSS 16.0 software for data analysis.3 Collect 35 cases serum specimen of hospitalized patients with drug eruption before and after treat,using trace sample m?ltiple protein quantitative technology to detect the serum complement proteins C3 a,C4a,C5 a expression level,and use the FCAP Array and SPSS 16.0 software for data analysis.4 Collect 30 cases peripheral blood of hospitalized patients with drug eruption,use the method of flow cytometry to dectet the proportion of CD4+ T and CD8+ T cells and Th1,Th2,Th17,Th22 cells in the proportion of CD4+ T cells,use Flowjo 7.6 and SPSS 16.0 software for data analysis.Results 1 Basic information of 194 patients with drug eruption Among the 194 cases of patients with drug eruption,.84 patients are male(43.2%),110 of them are female(56.4%).According to K-S inspection,the distribution of age data obey normal distribution,from1 year old to 87,and the average age is 48.46.The hospitalization cost is from1462.75 yuan to 73727.6 yuan.;The hospital stays of is from 1 day to 52 days;the incubation period is from 2 days to 53 days.There have different types of drug eruption : rashes sample drug eruption type,urticaria of drug eruption,fixed type of drug eruption,erythrodermic drug eruption,m?ltiform erythema type of drug eruption,Steven.John syndrome type and so on.Penicillin,cephalosporin,antiepileptic drugs and gout drugs are the main allergic drugs.Accroding to the grade of liver injury,divided all cases into three groups,the normal group,moderate damage,severe injury group.Then analyze the difference of immune related indexes in the three groups.the correlation analysis found that lymphocytes,monocytes,eosinophils is correlated with ALT,the immune response may play an important role in the drug eruption liver damage.2 Serum complement protein level Compared with healthy controls,patients with drug eruption before treatment had elevated levels of serum complement protein C3 a,C4a and C5 a,the difference was statistically significant(t = 2.832,P = 0.008;t = 2.257,P = 0.031,t = 2.495,P = 0.018).Compared with patient before treatment,after treatment the complement protein C3 a,C4a,C5 a were significantly reduced(t = 3.213,P = 0.003;t = 2.728,P = 0.010,t = 4.772,P < 0.001),the difference was statistically significant.After treatment the expression level of C3 a,C4a,C5 a were higher than the healthy controls,but there was no statistically significant difference(t = 1.097,P = 0.280;t = 0.293,P = 0.771;t = 1.103,P = 0.278).The correlation analysis found that the expression level of C3 a and ALT were positively correlated,C3 reduction of patients with drug eruption,may be due to the consumption of complement activation,and complement activation may play an important role in drug eruption liver damage.3 The serum cytokines level The serum expression level of IL-22,IL-13 in drug eruption patients and healthy controls were detected by enzyme-linked immunosorbent(ELISA).The serum IL-22 and IL-13 of drug eruption patients were higher than that of healthy controls,the difference was statistically significant(t = 5.549,P < 0.001;t = 6.071,P < 0.001;).The serum IFN – ? were higher than healthy controls,the difference was statistically significant(Z = 2.992,P = 2.992).The serum IL-2 and IL-4 expression level slightly higher than the healthy controls,there was no statistically significant difference in the two groups(Z = 0.396,P =0.396;Z = 0.649,P = 0.649).The serum TNF – ?,IL-6,IL-10 and IL-17 were higher than healthy controls,the difference was statistically significant(Z = 4.349,P = 4.349;Z = 4.584,P = 4.584;Z = 4.171,P= 4.171;Z = 2.972,P = 2.972).4 The T cells subgroup analysis res?lts We collected 30 cases whole blood specimens of drug eruption patients and healthy controls to do flow analysis,The statistical analysis of this study showed that compared with healthy controls,the percentage of CD4+T cell decline in the patients peripheral blood with drug eruption,difference was statistically significant(t = 4.231,P = 0.001);The percentage of CD8+T cells have a slightly raised,but there was no statistically significant difference(t = 0.836;P = 0.418);The CD4+ T /CD8+T ratio is reduced,and the difference was statistically significant(t = 3.134,P = 0.008).The res?lts show that compared with healthy controls,the proportion of Th1 cells in CD4+T cells increased obviously,difference was statistically significant(t=4.648;P <0.001);the proportion of Th2 cells in CD4+T cells were similar,and there was no statistically significant difference(t = 0.424,P = 0.678);Th1 / Th2 rise obviously,difference was statistically significant(t = 2.79;P = 0.015);the proportion of Th17 cells CD4+T cells increased obviously,the difference was statistically significant(t = 2.866;P = 0.013);the proportion of Th22 cells in CD4+T cells increased obviously,the difference was statistically significant(t = 5.016;P <0.001).Conclusions 1 The change of the immune related parameters of drug eruption patients may play an important role in liver damage.2 There exists complement activation in the process of drug eruption and complement activation may play an important reg?lating role in drug eruption liver damage.3 Compared with healthy controls,patients with drug eruption have an imbalanced Th1/Th2 and CD4+/CD8+ T in the peripheral blood.and higher percentage of Th1,Th17,Th22 cells in CD4+ T cells,and also higher level of their characteristic cytokines,Which indicate that Th1,Th17,Th22 may play important roles in the process of drug eruption.