Expression Of Cosmc, T-synthase MRNA In Peripheral B Lymphocytes And The Level Of Galactose-deficient IgA1 In Serum Of HSP Patients

Henoch-Schonlein purpura(HSP) is a common systemic small-vessel vasculitis. It occurs mainly in school-age children, and boys are more than girls, while adult cases are relatively few. The major clinical features include cutaneous purpura,abdominal pain or gastrointestinal bleeding, arthritis, and nephritis. In addition, few cases involve of genital or nervous system.The incidence of renal injury in HSP may be up to 50%[1], which means the poor prognosis of the disease. Although previous research about HSP has made some progress, the exact etiology and pathogenesis of HSP are still not well known. Current studies consider that many factors may relate to the disease,such as infectious, humoral and cellular immunity disorders, inheritance, food or drug allergies, coagulation and fibrinolytic system abnormality. Humoral immunity takes an important role in the pathogenesis of HSP,which B lymphocytes were overproliferated and overactivated,with increased Ig A1 secretion. Studies have shown that Ig A1 deposited extensively in skin, glomerular, and gastrointestinal mucous membrane of HSP patients[2-4]. The cause of Ig A1 deposition is not only owe to the increased production,but also largely depends on aberrant O-linked galactosylation in the hinge region of Ig A1 molecules. Galactosylation of Ig A1 is catalysed by T-synthase(also known as core1β3-galactosyltransferase,C1GALT1) and molecular chaperone Cosmc is necessary to the activity of T-synthase in vivo[5].So Cosmc and galactose-deficient Ig A1(Gd-Ig Al) may play important role in HSP’s pathogenesis.Objective:By investigateing the expression of Cosmc and T-synthase m RNA in peripheral B lymphocytes from patients with HSP and Gd-Ig Al level in their serum, try to explore their roles in the pathogenesis of HSP.Methods:1 Research Objects:The cases group include 56 HSP patients that recruit from the second Hospital of Hebei Medical University. Among them,30 were male and 26 were female, the age was from 6 to 42.The average age was 16.84±8.27 years old.The course of disease was a period from 2 days to 2 months.All of them have no allergic or autoimmune diseases,no cancer or other serious systemic diseases. Neither glucocorticoid nor immunosuppressants had been used for 4 weeks. Both blood platelet count and coagulation function were normal. Patients were divided into 4 groups according to clinical symptoms and laboratory examination results:(1) skin type- 22 cases;(2) joint type- 9 cases;(3) abdominal type- 12 cases;(4) kidney type- 13 cases. 20 healthy donors were enrolled in control group, the differences of age and gender between patients and healthy were not statistically significant.2 Research Methods:The m RNA expression of Cosmc and T-synthase in peripheral B lymphocytes from HSP patients and normal controls were measured by RT-PCR. Serum Gd-Ig A1 levels were quantified by an HAA-lectin-based ELISA. The results were analyzed via statistical software.3 Statistical Methods:Data were analyzed by statistical software SPSS19.0, statistical difference was considered if P<0.05. Normally distributed data were expressed by mean±standard deviation( x ±s).Median(Interquartile range) [MD(IQR)] was used when data does not comply with the normal distribution. One-way ANOVA or Kruskal-Wallis H test was used for comparison of multipole independent samples and the following pairwise comparisons were performed by LSD test or Nemenyi test. The Spearman’s rank correlation coefficient test were applied to assess correlations.Results:1 The relative expression values(RQ) of Cosmc m RNA in different sub-groups of HSP(skin type,0.849±0.239; joint type,0.767±0.181; abdominal type,0.719±0.183; kidney type,0.459±0.121)were all significantly lower than the normal control(1.146±0.232)(P<0.01). The expression of Cosmc m RNA in kidney type was especially lower than skin type, joint type,and abdominal type(P<0.01),but there were no significantly differences among the last three groups(P>0.05).2 The RQ values of T-synthase m RNA in different sub-groups of HSP(skin type,2.249±0.707; joint type,1.987±0.637; abdominal type,2.182± 0.589; kidney type, 1.837±0.883) and the normal controls(2.310±0.764) did not shown significantly differences(F=1.05,P=0.388).3 Serum Gd-Ig Al levels in different sub-groups of HSP [pure skin type, 1161.79(774.50) U/ml; joint type, 1345.84(795.74) U/ml; abdominal type, 1223.41(982.31) U/ml;kidney type, 1835.02(1090.55) U/ml] were all significantly higher than the normal control [839.10(587.07) U/ml](P<0.05). What’s more, the serum Gd-Ig Al levels in kidney type was significantly higher than skin type, joint type, and abdominal type(P<0.05),but there were no significantly differences among the last three groups(P>0.05).4 Serum Gd-Ig Al level were negatively correlated with relative expression value(RQ) of Cosmc m RNA(R=-0.496,P<0.01).Conclusions:1 There were decreased expression of Cosmc m RNA in peripheral B lymphocytes and elevated serum Gd-Ig Al in HSP.The two facters are negative correlated meanwhile.However,the expression of T-synthase m RNA was normal in HSP patients. So the increased serum Gd-Ig Al finally resulting in HSP may be heavily attributed to the decrease of Cosmc expression.2 Compaired with other three types of HSP, the degree of decreased expression of Cosmc m RNA in peripheral B lymphocytes and elevated serum Gd-Ig Al in kidney type were more significant.It means that the two factors are associated with renal involvement.3 Correcting such abnormalities in expression of Cosmc and serum Gd-Ig Al level may help HSP patients to get recovery and improve their prognosis.