Myasthenia gravis (MG) is a common antibody mediated, cell-mediated, and complement dependent neuromuscular junction immune disease. The treatment mainly includes drug therapy (symptomatic therapy, non-specific immunosuppressive therapy, targeted immunotherapy), immune regulation (intravenous injection of human immunoglobulin and plasma exchange), and thymectomy. With the continuous deepening of research on MG treatment, targeted immune regulation of B cells, complement system, and neonatal Fc receptors has become a current research hotspot in the treatment of MG. Compared with traditional immunosuppressants, MG patients have better tolerance to new biological agents. This article elaborates on the research of MG targeted therapy related drugs and summarizes their efficacy and safety in MG treatment, aiming to find more treatment options.
ObjectiveTo observe the effect of complement receptor 1 (CR1) on barrier of cultured human retinal epithelial cells (hRPE) under complement-activated oxidative stress. MethodsThe third to fifth passage of hRPE cultured on Transwell insert were used to establish a stable hRPE monolayer barrier. The hRPE monolayer barrier was exposed to 500 μmol/L ten-butyl hydroperoxide and 10% normal human serum to establish the hRPE monolayer barrier model of complement-activated oxidative stress in vitro. hRPE monolayer barriers under complement-activated oxidative stress were divided into two groups including model group and CR1 treatment (1 μg/ml) group. Model group and CR1 treatment group were treated with 1 μl phosphate buffer solution (PBS) or CR1 for 4 hours. Normal hRPE monolayer barrier were used as control in transepithelial resistance (TER) measurement experiment. TER was measured to evaluate the barrier function of hRPE. The hRPE-secreted vascular endothelial growth factor (VEGF) and chemokine (C-C Motif) Ligand 2 (CCL2), together with complement bioactive fragments (C3a, C5a) and membrane-attack complex (MAC) in the supernatant were detected by enzyme-linked immune sorbent assay. ResultsStable hRPE monolayer barrier was established 3 weeks after hRPE seeded on Transwell insert. Complement-activated oxidative stress resulted in a sharp decrease of TER to 54.51% compared with normal hRPE barrier. CR1 treatment could significantly improve TER of barrier under complement-activated oxidative stress to 63.48% compared with normal hRPE barrier(t=21.60, P < 0.05). Compared with model group, CR1 treatment could significantly decrease the concentration of VEGF and CCL2 by 11.48% and 23.47% secreted by hRPE under complement-activated oxidative stress (t=3.26, 2.43; P < 0.05). Compared with model group, CR1 treatment could also decreased the concentration of C3a, C5a and MAC by 24.00%, 27.87%, 22.44%.The difference were statistically significant (t=9.86, 2.63, 6.94; P < 0.05). ConclusionsCR1 could protect the barrier function of hRPE cells against complement-activated oxidative stress. The underlying mechanism may involve inhibiting complement activation and down-regulating the expression of VEGF and CCL2.
ObjectiveTo explore the serum concentrations of complement C1q tumor necrosis factor related protein 5 (CTRP5) in patients with acute exacerbations and stable stage of chronic obstructive pulmonary disease (COPD), and analyze the correlation of CTRP5 with high sensitivity C-reactive protein (hs-CRP) and FEV1/FVC and FEV1%pred.MethodsThirty hospitalized patients with acute exacerbation of COPD and 30 outpatients with stable COPD according with diagnostic criteria and inclusive criteria were sampled successively. At the same time 30 healthy volunteers were selected as normal control. All subjects were measured the concentrations of CTRP5 and hs-CRP in serum and lung function test was performed.ResultsThe serum CTRP5 and hs-CRP concentrations of the acute exacerbation group was higher than those in the stable group and the control group. The serum CTRP5 and hs-CRP concentrations of the stable group was also higher than those of the control group. The FEV1/FVC of the acute exacerbation group was lower than those of the stable group and the control group; and the FEV1/FVC of the stable group was lower than that of the control group. The FEV1%pred of three groups by analysis indicated the difference was statistically significant. Further pairwise comparisons demonstrated that the FEV1%pred of two COPD groups were lower than that of the control group but the FEV1%pred of the acute exacerbation group and stable group was not significantly different. The correlation analysis of the acute exacerbation group and the stable group demonstrated that the levels of serum CTRP5 and hs-CRP were postively correlated and the level of serum CTRP5 was negatively correlated with FEV1/FVC and FEV1%pred.ConclusionsThe level of CTRP5 in serum of COPD patients is increased. No matter in acute exacerbation or stable phase, the level of serum CTRP5 is positively correlated with hs-CRP and negatively correlated with FEV1/FVC and FEV1%pred, which suggests that CTRP5 is involved in the pathogenesis of COPD but the exact mechanism needs further study.
Thirty patients with obstructive jaundice were investigated for serum complement-3 (C3) and plasma fibronectin (FN).The levels of C3 and FN of the juandiced patients were higher than that of thirty patients without obstructive jaundice (Ｐ＜0.01). As compared to pre-operation, the level of C3 of the jaundiced patients decreased obviously within two weeks after operation(Ｐ＜0.01), and recovered in the third week after operation. The level of FN of the juandice patients decreased evidently within one week(Ｐ＜0.01), and recovered in the second week after operation. However, the levels of C3 and FN of the patients without obstructive jaundice changed slightly after operation (Ｐ＜0.05). The high levels of C3 and FN of jaundiced patients may be relative to the latent infection. Consumption and immune imparing may be the reasons of C3 and FN to decrease.
摘要:目的:动态观察大鼠脑出血后血肿周围组织补体激活与细胞凋亡的规律。方法:用胶原酶注入到大鼠尾状核的方法制作脑出血模型。将大鼠分为脑出血、假手术组、正常组3组。采用苏木素伊红(HE) 染色、免疫组织化学染色及原位末端脱氧核苷酸转移酶介导的dUTP 缺口末端标记法(TUNEL)分别观察各组在脑出血后第6 h、12 h、24 h、48 h、72 h、5 d、7 d时血肿周围补体C3、促凋亡基因(Bax)、抑凋亡基因(Bclxl)及TUNEL的表达。结果补体C3的表达峰值在24~48 h;TUNEL、Bax蛋白表达术后12h增加,48~72 h达高峰,而Bclxl蛋白表达高峰在48h。结论:大鼠脑出血后血肿周围组织补体C3的表达增加与细胞凋亡的演变趋势一致,C3与凋亡有相关。Abstract: Objective: To study the complement activation and apoptosis regular genes changes in the tissues of the perihematoma of intracerebral hemorrhage (ICH) in rats. Methods: Intracerebral hemorrhage was induced in rats by injection of bacterial collagenase into the caudate nucleus. Histopathological changes were studied in 6 h,12 h, 24 h, 2 d, 3 d, 5 d, 7 d after the injection. The immunohistochemistry and TUNEL analysis were performed. The expression of complement factor C3, the TUNELpositive cells, the proapoptotic gene expression (Bax) and the antiapoptotic gene (Bclxl) were examined. Results: The expression of C3 increased to its maximum between 2448 h. The TUNELpositive cells and Bax protein expression increased gradually and reached the peak level between 4872 h. The Bclxl protein reached the peak level at 48 h. The correlation analysis showed that the quantity of C3 was positively related to that of the TUNELpositive cells, but the bax protein was not related to Bclxl protein. Conclusion: The expression of complement factor C3 may contributes to the nerve injury after cerebral hemorrhage and relate to the apotosis in the tissues surrounding the hametoma in rats.
Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
ObjectiveTo understand the role of complement system in the immune mechanism of hepatocellular carcinoma (HCC) and its potential therapy value. MethodThe national and international literature relavant researches of complement system in the HCC was reviewed. ResultsBased on HCC as an immunogenic cancer and the complement system as a part of the innate immune system, it had potential application value in immunotherapy. Eight complement components (complement intrinsic components C1q, C3, and mannose binding lectin, soluble regulatory proteins complement factor H and C4b, and membrane regulatory proteins CD46 and CD59, as well as complement receptor C5aR1) were closely associated with HCC. The activation of the complement system could participate in the occurrence and development of HCC through various mechanisms. The complement inhibitor, it could regulate the activity of complement related activation pathways, enhance anti-tumor ability, and provide a potential new strategy for immunotherapy of HCC. ConclusionsAt present, only a few complement components have been found in HCC research. Although it has been found that multiple complement components play a role in regulating the immune mechanism of HCC, there is still no definite or recognized theoretical basis. In the future, further exploration of the protective or pathogenic mechanisms of complement components in HCC immunity is needed to objectively evaluate the risks and benefits of complement related inhibitor therapy and in combination with other anti-tumor immune therapies.