| Backgrounds and Aims:Immunoglobulin A nephropathy (IgAN) is an autoimmune disease and is very common form of primary glomerulonephritis. It occurs worldwide with different frequency from 2% to 52% of all renal diseases in different parts of the world. Cellular and humoral immune abnormalities with T-cell dysfunction and imbalance of Th1/Th2 cytokines are proposed to play an important role in the development of IgAN. Human T-cell Immunoglobulin Domain and Mucin (Tim) family represent relatively newly described immune regulators. The Tim family is located on chromosome 11B1.1 in mice and consists of four identified members (Tim-1,-2,-3, and -4) and four putative members (Tim-5,-6,-7, and -8). All are predicted to be type Ⅰ membrane proteins that share a characteristic immunoglobulin V (Ig V), mucin, transmembrane and cytoplasmic domain structure. Tim-3 is expressed on T helper type 1 (Th1) cells and implicated in the pathogenesis of Thl-driven auto- and allo-immune diseases in both mice and human.Many previous studies have demonstrated that Tim-3 influences chronic autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis. Some studies showed that the expression of Tim-3 and related cytokines in peripheral blood mononuclear cells (PBMC) from patients with IgAN, but so far, there is no report on the expression of Tim-3 in renal tissue from patients with IgAN and compared with normal renal tissue from patients without the disease.In recent years, there are few reports of the Tim protein and genes family in the development of IgAN. In the study, the researchers adopt the method of case-control study, from serology and pathology to explore the expression of Tim-3 in IgAN and without IgAN, and analysis the relationship between the serum and pathology level of Tim-3 and IgAN activity.Methods:Peripheral blood was obtained from patients including IgAN-group and control-group in the next morning after admission and fasting 8 hours to determine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). The count of red blood cell (RBC), count of white blood cell (WBC), count of platelet (Plt), proteinuria, the concentration of IgA in serum was also examined. Patients in IgAN-group were accepted percutaneous renal biopsy (PRB) after informed consent about the necessity and risk. In control-group, all selected candidates received renal hamartoma resection, which depended on pathological diagnosis, and normal kidney tissue next to hamartoma was selected, non-hamartoma in pathology, to detect expression of Tim-3. Histological examination of the renal tissues in both groups was carried out following PAS staining of paraffin embedded sections. We applied the semi-quantitative evaluation, an immunoreactivity-scoring system (IRS), to evaluate the expression of Tim-3 on renal tissue. We used the method to assess differences between the IgA-group and control-group.The study protocol was approved by the ethics committee of the hospital, and written informed consent was obtained from all patients after they reviewed a written summary of the study plan. All patients gave informed written consent for analysis of their tissue for research purposes.Results:1.Expression of Tim-3 in renal tissue of IgAN:Positive staining of Tim-3 protein was seen in 94.3% patients with IgA nephropathy (67 out of 71), but 84.6% negative staining in the cases without IgAN (11 out of 13), only 2 out of 13 patients in control-group were positive staining of Tim-3. When the expression of Tim-3 protein was further compared by semiquantitative immunoreactivity H-scoring, renal tissue in IgAN-group displayed a much higher Tim-3 score than control-group renal tissue (2.207 ± 0.613 vs 0.108 ± 0.001, P< 0.001).2.Relationship between pathology classes of IgAN and expression of Tim-3:The present study indicated that there was a nearly positive correlation between pathological manifestations of IgAN and expression degree of Tim-3.3.Expression of Tim-3 was correlated with serological parameters:We correlated the Tim-3 expression data to serological parameters such as ESR, CRP, RBC, WBC, Plt, proteinuria and the concentration of IgA in serum. The degree of expression for Tim-3 was found to be significantly correlated with serological parameters (P<0.001). High expression of Tim-3 was significantly correlated with concentration of ESR, CRP, proteinuria and IgA in serum.Conclusions:The expression of Tim-3 in renal tissue was detected in patients with IgAN, and was associated with the diseases’ activity. But there was almost no expression of Tim-3 in renal tissue from benign tumor. Whether there is a change for Tim-3 expression in IgAN after treatment requires further study. The results were valid using the anti-Tim-3 polyclonal antibody and that they should be confirmed using anti-Tim-3 monoclonal antibodies. We speculate that the high expression of Tim-3 was seen in other immune-related kidney diseases besides IgAN by using polyclonal antibody or/and monoclonal antibodies, because most kidney diseases were correlated with immune imbalanceBACKGROUND AND PURPOSE; SLE 巧ystemic Lupus Erythematosus, SL巧 is a multi-factor(genetics, hormones, environment, infections, drugs, various aspects of the immune response) specifically involved in autoimmune diseases. The development of SLE patients with up 化 60% of kidney involvement, namely the development of lupus nephritis(lupus nephritis, LN),LN incidence of racial differences exi巧 betwee打 the relevant Chi打的e experts found that the incidence of patients in China rate is relatively high. LN SLE is an important cause of death,but also the patients developed ESRD(end-stage kidney disease, ESRD) important reaso打s. Iimmmc-rdated diseases is mai打ly due to imimmc dysflmctio打,Tesulti打g in 江corresponding adjustment 巧ssue and organ damage caused by the disease,autoimmune disease refers to the body’s own immune response to antigens resulting巧ssue damage cau化d by their 出化ase. Numerous studies show that 汪 variety of immune regulatory molecules play an important role in 化6 pathogenesis of LN.Tim-3 is an important member of the Tim gene family, the family is located on human chromosome 5. Tim-3 specifically expr的sed on activated Thl cell surface.With further reisearch: it was found that 了iin-3 is curre打tly only expressed on activated Thl ceUs,also expressed i打 a variety of immune cells,C了L,DC and NK cells,江variety of immune-related infection, cancer and organ transplant rejection, such as after the play an important role in 化e 化化ase. Many studies have shown that 化e development of Tim-3 chronic autoimmune 出seases such as multiple sclerosis (Multiple Sclerosis), rheumatoid arthritis(Rheumatoid Arthritis). Some studio sugge巧 that, Tim-3 expression in immunoglobulin IgAN patients peripheral blood mononuclear cells associated cytokines(Peripheral 村ood mononuclear cdl-associated cytokines, PBMC) in. In recent years, at home and abroad about whether Tim genes and proteins involved in the development of LN rarely reported,in view of this,化is study wHl serological LN patients,kidney 巧ssue of Tim-3 expressio打,也e expre巧km of Tim-3 clinical LN 化 study the wlationship between the classification and the relationship between Tim-3 expression and serological parameters between patients wkh LN.Methods: In this study, 65 cases of LN patients as 化e study group(50 wome打 andl5 men,mean age 43.8±6.1 years old,were more than 18 years old),all patient visits 泣particular Nephrology three hospitals, treatment time between May 20111;o May2014, were enrolled in this study had been diagnosed with renal biopsy lupus nephritis,all patients GF民含90 mL / min 1.73 meters,moi"e than 18 years of age, be excluded and allergy-related diseases(such as asthma or allergic rliinkis) and treatment of immune modulation therapy, all selected objects without diabetes, liver dysfunction and abnormal hyperlipoproteinemia. Sale巧 the same time in 江 hospital urology hospital 19 patients(surgery and pathology of renal angiomyolipoma) as the control group(5 men and 14 women,mean age 42.1±5.7 years),all patients i打化e control group were aged over 18 years old, GFR>90 mL / min 1.73 meters, all enrolled in the control group who had no 姐abetes,a history of liver dysfimction,abnormal lipoprotein hyperlipidemia, asthma or allergic rhinitis and other allergic diseases. All patie打ts enrolled i打 the study,morning fasting peripheral blood,testing complement 3(C3),complement 4(C4),ES民,CRP,RBC, WBC,PLT,urine protein,anti-double stranded DNA antibody(anti-dsDNA), anti- Sm antibodies, anti-ANA antibodies. LN group signed the informed consent, underwent percutaneous renal biopsy. In the control group, all selected underwent resection of renal hamartoma, hamartoma take its adjacent histologically confirmed non-pathological 出agnosis of hamartoma normal renaUissue.Results: 1 reflects LN serological activity indicators were higher than noir-LN patients,and the 出fference between the two groups was significant. 2. Tim-3 protein was seen in 96.9% of LN patients(63/65), but 94.7% of the non-LN-negative patients(18/19) in the control group, only one cases of Tim-3 positive staining. Further semiquantitative immunoreactivity measwed H- score Tim-3 protein expression, LN Tim-3 group scored significantly higher, the difference was statistically significant.There was 过 positive correlation between the pathological manifestatio打5 and the level of Tim-3. 3. The severity of the symptoms and the expression of Tim-3 degree between were positively correlated. 4. High immune Ksponse Tim-3 and serological parameters(C3, C4, ESR,CRP,RB。WB。PLT,proteinuria^ dsDNA,anti-Sm and ANA) grading(P <0,001) were significantly associated in LN, and in the control group they had no significant correlation.Condusions: Systemic lupus erythematosus is an immune-related 出sease,we used anti-Tim-3 polyclonal antibody 化 study the Tim-3 expression in SLE group and the control group,and confirmed 化e detectio打 of renal tissue in patie扛ts with SLE 化 Tim-3 expression and the activity of the disease related. Because moist kidney diseases are associated with immune imbalance, we hypothesized that through the use of polyclonal and / or monoclonal antibodies,in other immune-related kidney disease can be detected with high expression of Tim-3. |
PDF Full Text Request