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Shu-Fen Zhou,
Ji Ma,
Hui-Ting Qu,
Zong-Tang Liu,
Wei-Dong He,
Juan-Dong Wang,
Ai-Xia Dou,
Ni Zhang,
Jun-Li Liu,
Cheng-Shan Guo,
Yan Shi,
Ming Hou, Jun Peng
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ABSTRACT: PURPOSE: In view of the numerous clinical observations and laboratory studies that suggest a critical role for the spleen in immune thrombocytopenia (ITP) pathophysiology, we aimed to characterize Th1-associated chemokine receptors CXCR3 and CCR5 and Th2-associated chemokine receptor CCR3 in spleens of ITP patients and assess the significance of their differential expression in the clinical setting. METHODS: The histopathology of spleens was observed using hematoxylin-eosin staining (HE), and the positive rate of CXCR3, CCR5 and CCR3 expression in spleens of 24 ITP patients and 12 patients with traumatic splenic rupture as normal controls was detected by immunohistochemistry using the SP method. CXCR3, CCR5 and CCR3 protein expression was analyzed by Western blot and mRNA levels were investigated by real-time polymerase chain reaction (RT-PCR). RESULTS: Reactive hyperplasia could be seen in follicles of the white pulp, the germinal central zone was enlarged and the marginal zone was thickened, the central arteries were thickened and fibrotic, and the density of the capillary vessel was increased in ITP patients. ITP group displayed a higher rate of expression of Th1-associated chemokine receptors CXCR3 and CCR5 (83.3 % vs. 75 %, 100 % vs. 83.3 %) but lower rate of expression of Th2-associated chemokine receptor CCR3 (50 % vs. 66.7 %) compared with the controls (P < 0.05, respectively). Western blot analysis revealed that CXCR3 and CCR5 protein expression was significantly increased in ITP patients while CCR3 was significantly reduced (P < 0.05, respectively). Meanwhile, ITP patients displayed increased mRNA levels of CXCR3 and CCR5 but decreased gene expression of CCR3 (P < 0.05, respectively). CONCLUSION: The data suggested that the abnormal expression of Th1/Th2 chemokine receptors may participate in splenic immune disorder in patients with ITP. Using corresponding inhibitors may inhibit Th1-dominant expression and mitigate the progress of the disease.
Journal of Clinical Immunology 03/2013; · 3.08 Impact Factor
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Hui-Zhen Du,
Qian Wang,
Jian Ji,
Bao-Ming Shen,
Shao-Chun Wei,
Li-Juan Liu,
Juan Ding,
Dao-Xin Ma,
Wen Wang, Jun Peng,
Ming Hou
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ABSTRACT: BACKGROUND: Aplastic anemia (AA) is an autoimmune disease and interleukin-27 (IL-27) is an important cytokine involved in the pathogenesis of autoimmune diseases. To date there have been no reports concerning the intrinsic association among IL-27 and Thelper (Th) 1 and Th17 cells in AA. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) to assay IL-27, interferon gamma (IFN-γ) and IL-17 levels, flow cytometry to measure the percentages of Th1 and Th17 cells among peripheral blood mononuclear cells (PBMCs), real-time reverse transcriptase polymerase chain reaction (PCR) for the mRNA levels of IL-27, IFN-γ, T-bet and IL-17 and retinoid related orphan receptor gamma (RORγt) in PBMCs were performed. In addition, the effect of exogenous rhIL-27 on the differentiation of T cells into Th1 and Th17 cells was investigated in vitro. RESULTS: Plasma and mRNA levels of IL-27 in PBMCs from AA patients were significantly higher than those in healthy controls. A positive correlation was found between plasma levels of IL27 and IFN-γ. The proportions of Th1 and Th17 cells accompanied by the mRNA expression of RORγt and T-bet were significantly higher in AA patients than in healthy controls. Plasma levels of IL-27 correlated positively with frequencies of Th1 cells in AA patients. Exogenous rhIL-27 could significantly upregulate the frequency of Th1 cells and the mRNA levels of T-bet and IFN-γ and the application of rhIL-27 in vitro could inhibit the expression of RORγt mRNA. CONCLUSION: The upregulation of IL-27 might cause Th1 differentiation and immune disorders in AA patients. Blocking the expression of IL-27 could therefore be a reasonable therapeutic strategy for AA.
Journal of Clinical Immunology 09/2012; · 3.08 Impact Factor
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Yu Hu,
Haiyan Li,
Lei Zhang,
Baozhong Shan,
Xingfang Xu,
Hong Li,
Xinguang Liu,
Shuqian Xu,
Shuang Yu,
Daoxin Ma, Jun Peng,
Ming Hou
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ABSTRACT: T-helper (Th) 22 and Th17 cells are implicated in the pathogenesis of autoimmune diseases. However, the role of Th22 cells in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Th22, Th17 and Th1 cells in both ITP patients and healthy controls were examined by flow cytometry. Plasma interleukin-22 (IL-22) level was measured by enzyme linked immunosorbent assay (ELISA). Signal transducers and activators of transcription 3 (STAT-3) and transcription factor RAR-related organ receptor C (RORC) messenger RNA (mRNA) expressions were examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Th22 cells, Th17 cells, Th1 cells and plasma IL-22 were significantly higher in ITP patients than in healthy controls. Moreover, Th22 cells showed a positive correlation with the levels of plasma IL-22 as well as Th17 and Th1 cells in ITP patients. Significant up-regulations of both STAT-3 and RORC transcription factors were also observed. Additionally, the percentage of Th22 cells was higher in autoantibody-negative ITP patients than in autoantibody-positive patients. Our results demonstrate a possible role of Th22 cells in ITP, and thus, the blockade of IL-22 may be a reasonable therapeutic strategy for ITP.
Human immunology 04/2012; 73(6):629-35. · 2.55 Impact Factor
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Shu-Qian Xu,
Chun-Yan Wang,
Xiao-Juan Zhu,
Xiao-Yuan Dong,
Yan Shi, Jun Peng,
Ping Qin,
Jian-Zhi Sun,
Chengshan Guo,
Heyu Ni,
Ming Hou
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ABSTRACT: Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) can induce or maintain peripheral immune tolerance. Impaired IDO-mediated tryptophan catabolism has been observed in autoimmune diseases. In order to investigate the effects of IDO-mediated tryptophan catabolism and IDO-expressing DCs in immune thrombocytopenia, the concentrations of kynurenine were detected by high-pressure liquid chromatography. The expressions of IDO were analyzed by flow cytometry and western blot analysis. The effects of IDO(+) DCs stimulated with CTLA-4-Ig on T cells proliferation and activation, lymphocyte apoptosis, and Tregs were measured by flow cytometry. We found that the expression of IDO in DCs of immune thrombocytopenia (ITP) patients was significantly decreased. CTLA-4-Ig significantly increased the expression of functional IDO in DCs of ITP patients. IDO(+) DCs stimulated with CTLA-4-Ig suppressed T cells proliferation and activation, promoted lymphocyte apoptosis, and increased the percentage of Tregs. These results suggest that decreased IDO expression in DCs may play a critical role in ITP. CTLA-4-Ig successfully corrected the disorder of IDO expression in ITP. IDO(+) DCs stimulated with CTLA-4-Ig inhibited immune responses by an IDO-dependent mechanism. Increasing the expression and activity of IDO in DCs might be a promising therapeutic approach for ITP.
Annals of Hematology 04/2012; 91(10):1623-31. · 2.62 Impact Factor
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Qianqian Shao,
Hao Ning,
Jiaju Lv,
Yanguo Liu,
Xin Zhao,
Guangwen Ren,
Alei Feng,
Qi Xie,
Jintang Sun,
Bingfeng Song,
Yongmei Yang,
Wenjuan Gao,
Kejia Ding,
Meixiang Yang,
Ming Hou, Jun Peng,
Xun Qu
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ABSTRACT: Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder-primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.
Blood 03/2012; 119(20):4636-44. · 9.90 Impact Factor
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ABSTRACT: Supraglottic jet ventilation (SJV) via the "jet endotracheal tube" (JET) designed by Wei (WEI JET; Wei Medical LLC, Cherry Hill, NJ) provides adequate oxygenation and ventilation during direct laryngoscopy and tracheal intubation in animals. It has facilitated intubation in apneic pigs with a simulated difficult airway.
To report on the first clinical study to examine the efficacy of using SJV via the WEI JET, in combination with end-tidal CO(2) pressure (PetCO(2)) monitoring during SJV, in maintaining oxygenation during direct laryngoscopy, and in facilitating placement of the WEI JET, and comparing it to the standard intubation technique using a conventional endotracheal tube. The relative safety of using SJV via the WEI JET in airway management was also addressed to provide the foundation for a larger-scale clinical study using the WEI JET, to be carried out in the future.
Patients in the control group were intubated with a conventional endotracheal tube, and patients in the experimental group were intubated with a WEI JET. The effectiveness of SJV through a WEI JET in maintaining proper oxygenation, and the use of PetCO(2) monitoring to facilitate intubation, were studied and compared to the control group. Complications such as sore throat, laryngospasm, and barotrauma were recorded during the study and 24 h after extubation.
In the WEI JET group, pulse oxygen saturation (SpO(2)) was 100% in all patients during intubation. No serious complications were detected, and the incidence of minor complications was comparable to the control group. Under PetCO(2) guidance, 100% of patients in the WEI JET group were intubated on the first attempt, compared to 30% of Grade III view patients in the control group, who required two attempts.
Using the WEI JET with SJV provides adequate oxygenation during tracheal intubation in apneic patients for a prolonged period of time, with no difference in complications compared to the standard intubation technique. PetCO(2) monitoring facilitated intubation in patients with a Grade III glottis view.
Journal of Emergency Medicine 03/2012; 43(2):382-90. · 1.31 Impact Factor
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ABSTRACT: Carbon monoxide (CO) exposure at high concentrations results in overt neurotoxicity. Exposure to low CO concentrations occurs commonly yet is usually sub-clinical. Infants are uniquely vulnerable to a variety of toxins, however, the effects of postnatal sub-clinical CO exposure on the developing brain are unknown. Apoptosis occurs normally within the brain during development and is critical for synaptogenesis. Here we demonstrate that brief, postnatal sub-clinical CO exposure inhibits developmental neuroapoptosis resulting in impaired learning, memory, and social behavior. Three hour exposure to 5 ppm or 100 ppm CO impaired cytochrome c release, caspase-3 activation, and apoptosis in neocortex and hippocampus of 10 day old CD-1 mice. CO increased NeuN protein, neuronal numbers, and resulted in megalencephaly. CO-exposed mice demonstrated impaired memory and learning and reduced socialization following exposure. Thus, CO-mediated inhibition of neuroapoptosis might represent an important etiology of acquired neurocognitive impairment and behavioral disorders in children.
PLoS ONE 01/2012; 7(2):e32029. · 4.09 Impact Factor
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Lin-Lin Shao,
Lei Zhang,
Yu Hou,
Shuang Yu,
Xin-Guang Liu,
Xiao-Yang Huang,
Yuan-Xin Sun,
Tian Tian,
Na He,
Dao-Xin Ma, Jun Peng,
Ming Hou
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ABSTRACT: Immunological mechanisms are increasingly recognized in the progression of myelodysplastic syndrome (MDS). Early-stage MDS (E-MDS) is characterized by autoimmune-mediated myelosuppression whereas late-stage MDS (L-MDS) involves immune evasion, giving dysplastic cells growth potential to progress into acute myeloid leukemia. T-helper (Th) 22 is involved in the pathogenesis of inflammatory autoimmunity and tumorigenesis. The roles of Th22 cells in the pathophysiology of E-MDS and L-MDS remain unsettled.
We studied 37 MDS patients (E-MDS, n = 17; L-MDS, n = 20) and 20 healthy controls to characterize their peripheral blood (PB), as well as 25 MDS patients and 10 healthy controls to characterize their bone marrow(BM). The expression of Interleukin-22 (IL-22), IL-17 or interferon gamma (IFN-γ) was examined in E-MDS, L-MDS patients and controls by flow cytometry. The mRNA expression levels of RAR-related orphan receptor C (RORC), IL-6, tumor necrosis factor alpha (TNF-α) and IL-23 in peripheral blood mononuclear cells (PBMCs) were determined by real-time quantitative polymerase chain reaction. The levels of IL-22 and IL-17 both in PB and BM plasma were examined by enzyme-linked immunosorbent assay.
In E-MDS, peripheral Th17 cells were significantly elevated and correlated with peripheral Th22 cells compared with healthy controls and L-MDS. Significantly higher levels of peripheral Th22 expansion, mRNA expression of IL-6, TNF-α and lower level of RORC mRNA expression were observed in L-MDS compared with E-MDS. No statistical difference was found in IL-23 mRNA expression or plasma IL-22, IL-17 levels among E-MDS, L-MDS and controls.
Our data demonstrated that L-MDS cohort had increased frequencies of peripheral Th22 cells and higher mRNA expression levels of IL-6 and TNF-α, indicating that Th22 cells along with Th17 cells or not are involved in the dynamic immune responses of MDS.
PLoS ONE 01/2012; 7(12):e51339. · 4.09 Impact Factor
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Annals of Hematology 05/2011; 90(5):599-600. · 2.62 Impact Factor
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ABSTRACT: Indoleamine 2,3-dioxygenase (IDO) can promote peripheral immune tolerance and control autoimmune responses through tryptophan catabolism. Tryptophanyl-tRNA synthetase (TTS) can protect T cells from IDO-mediated cell injury. Impaired IDO-mediated tryptophan catabolism has been observed in some autoimmune diseases.
The concentrations of plasma kynurenine and tryptophan were detected by high-pressure liquid chromatography. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry.
Compared with healthy controls, the PBMCs of patients with immune thrombocytopenia (ITP) had significantly increased expressions of IDO and TTS, especially IDO. However, the plasma tryptophan concentration was significantly elevated, and kynurenine concentration was significantly reduced in ITP patients. In CD4(+) and CD8(+) T cells of the ITP patients, IDO expressions were significantly lower than those in healthy controls, but in CD19(+) and CD14(+) cells, IDO expression significantly increased. Conversely, TTS expressions in CD4(+) and CD8(+) T cells of the ITP patients were significantly higher than those in healthy controls, but there was no difference either in CD19(+) or CD14(+) cells.
These results suggest that the activity of IDO enzyme is insufficient in ITP patients. Increased TTS expressions from CD4(+) and CD8(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in ITP patients.
Journal of Clinical Immunology 04/2011; 31(4):643-9. · 3.08 Impact Factor
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ABSTRACT: T helper 1 cell (Th1) polarization persists in the autoimmune response found in immune thrombocytopenia (ITP). Toll-like receptor 7 (TLR7) expression, which also plays an important role in autoimmune diseases, was verified to increase in ITP. However, the exact role of TLR7 in ITP is not well elucidated. Here, we explored the hypothesis that TLR7 participates in the pathophysiology of ITP by affecting Th1 polarization.
Twenty-two ITP patients and twenty-one controls were enrolled in this study. We examined the cytokine secretion of macrophages in ITP patients and controls using both TLR7 agonist (imiquimod) and antagonist (IRS 661). The influence of macrophage secretion from these groups and its effects on Th1/Th2 differentiation were subsequently studied. Effects of TLR7 on Th1/Th2 balance and platelet counts were also studied in vivo using a thrombocytopenic mouse model.
In in vitro assays, imiquimod enhanced interleukin (IL)-12 secretion in macrophages from ITP patients inducing Th1 differentiation. However, IRS 661 had the exact opposite effect and skewed Th differentiation towards the Th2 subset in ITP. Results from our in vivo studies indicated that injection of imiquimod in ITP mice resulted in elevated plasma levels of IFN-γ and decreased platelet counts. Nevertheless, injection of IRS 661 resulted in elevated plasma levels of IL-4 and platelet counts.
These findings indicate that TLR7 promotes Th1 polarization and may contribute thus in the pathogenesis of ITP.
Thrombosis Research 03/2011; 128(3):237-42. · 2.44 Impact Factor
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Xin-guang Liu,
Juan Ren,
Yuan Yu,
Lin Sun,
Yan Shi,
Ping Qin,
Lei Yang,
Shi-hui Ma,
Xiao-yuan Dong,
Dao-xin Ma,
Xun Qu,
Cheng-shan Guo,
Chun-yan Chen,
Ming Hou, Jun Peng
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ABSTRACT: Primary immune thrombocytopenia (ITP) is an immune-mediated disorder in which disturbed cytokine profiles have been found. Interleukin-27 (IL27) has been shown to bear both proinflammatory and anti-inflammtory effects. In the present study, plasma levels of IL27, interferon gamma (IFNG), IL4, and IL17A were determined by enzyme-linked immunosorbent assay in 23 active ITP patients, 20 patients in remission and 20 healthy controls. mRNA expression levels of IL27, EBI3, IL27 receptor (IL27RA), IL17A and RAR-related orphan receptor C (RORC) were determined by real-time quantitative polymerase chain reaction. Significantly lower levels of plasma IL27, IL4, mRNA expression of IL27, EBI3 and higher levels of plasma IFNG as well as mRNA expression of IL17A, RORC were observed in active ITP patients compared with healthy controls or patients in remission. No statistical difference was found in IL27RA mRNA expression or plasma IL17A levels among active ITP patients and controls. A negative correlation was found between the IL27 and RORC mRNA expression levels in active ITP patients. Our data demonstrated that active ITP patients had decreased plasma and mRNA expression levels of IL27, suggesting that it might be involved in the pathophysiological process of ITP.
British Journal of Haematology 03/2011; 153(2):259-67. · 4.94 Impact Factor
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Xin-guang Liu,
Shi-hui Ma,
Jian-zhi Sun,
Juan Ren,
Yan Shi,
Lin Sun,
Xiao-yuan Dong,
Ping Qin,
Cheng-shan Guo,
Ming Hou, Jun Peng
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ABSTRACT: The human Fcγ receptor (FcγR) system is composed of 2 opposing families, the activating FcγRs (FcγRI, FcγRIIa, and FcγRIII) and the inhibitory FcγR (FcγRIIb). The disturbed balance of the activating and inhibitory FcγRs has been implicated in the pathogenesis of many autoimmune diseases. In this study, the expression of FcγRs on monocytes was determined in 23 patients with primary immune thrombocytopenia (ITP) before and after high-dose dexamethasone (HD-DXM) treatment. The FcγRI expression was significantly higher in ITP patients and decreased after HD-DXM treatment. The ratio of FcγRIIa/IIb mRNA expression on monocytes was significantly higher in untreated patients than in healthy controls. After HD-DXM therapy, the ratio decreased and the increased expression of FcγRIIb mRNA and protein coincided with a remarkable decrease in the expression of FcγRIIa, FcγRI, and monocyte phagocytic capacity. There was no significant difference in FcγRIII expression on monocytes between patients and controls. In vitro cell-culture experiments showed that DXM could induce FcγRIIa and FcγRIIb expression in monocytes from ITP patients, with FcγRIIb at higher amplitudes. These findings suggested that the disturbed FcγR balance might play a role in the pathogenesis of ITP, and that HD-DXM therapy could shift monocyte FcγR balance toward the inhibitory FcγRIIb in patients with ITP.
Blood 02/2011; 117(6):2061-9. · 9.90 Impact Factor
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ABSTRACT: Taking spatial information technology application in Xinjiang Production and Construction Corps (XPCC) as background, and considering special management features of XPCC, we propose a spatial information management and service model based on Web services and SOA architecture. We design the architecture and logical structure of XPCC-oriented distributed spatial information management and service platform, and put forward the special business system operating mode based on SOA architecture and fusion mechanism for spatial information resources and products. We implement the platform system and various special business systems based on ESRI product development framework, and validated the model system, which provides an application case for design and implementation of region-oriented distributed spatial information resource management and sharing service system.
Computational and Information Sciences (ICCIS), 2010 International Conference on; 01/2011
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ABSTRACT: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by anti-platelet autoantibody-mediated platelet destruction. Antigen-presenting cell (APC) dysfunction is considered to play crucial roles in ITP. However, how APC affects autoreactive B cells in ITP is still unknown. Using a mouse model of immune thrombocytopenia, we demonstrated an increase in levels of TLR7 in splenic mononuclear cells (SMCs). Using both TLR7 agonist and TLR7 silencing lentivirus, we found stimulation of TLR7 decreased platelet counts and increased levels of platelet-associated IgG (PAIgG) in ITP mice, which correlates TLR7 with platelet destruction by autoantibodies. Levels of serum BAFF increased significantly in ITP mice and stimulation of TLR7 promoted secretion of BAFF. Among the three BAFF receptors, only BAFF receptor (BAFF-R) increased in ITP mice. However, activation of TLR7 showed no effect on the expression of BAFF receptors. These findings indicate that upregulation of TLR7 may augment BAFF secretion by APC and through ligation of BAFF-R promote autoreactive B cell survival and thus anti-platelet autoantibody production. The pathway of TLR7/BAFF/BAFF-R provides us with an explanation of how activation of APC affects autoantibody production by B cells in ITP and thus might provide a reasonable therapeutic strategy for ITP.
PLoS ONE 01/2011; 6(7):e22708. · 4.09 Impact Factor
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ABSTRACT: To investigate the role of IL-18 and IL-18BP balance in the spleens of patients with primary immune thrombocytopenia (ITP).
A total of 12 active ITP patients and 10 normal controls were recruited. Their expressions of IL-18 and IL-18BP were measured by immunohistochemistry (IHC) and immunofluorescence. The mRNA expressions of IL-18, IL-18BP, IFN-γ and IL-4 were studied by reverse transcription-polymerase chain reaction (RT-PCR) in all subjects.
The positive rate of IL-18 was higher in the ITP patients than that of the normal control group (100% vs 90.0%). And the positive rate of IL-18BP was higher in the ITP patients than that of the normal control spleen (83.3% vs 60.0%). The relative amount of mRNA gene expression of IL-18 was increased 6.0-fold in active patients compared to controls (P<0.05). But the elevated mRNA content of IL-18BP failed to compensate for the sharply elevated content of IL-18. As compared with the normal control group, the expression level of IFN-γ mRNA expression was significantly increased 10.2-fold in ITP patients (P<0.05). The decrease observed in IL-4 was 41.7% in active patients compared to controls (P<0.05).
The IL-18/IL-18BP imbalance plays an important role in pathogenesis of ITP and its correction may become a potential therapeutic target for ITP.
Zhonghua yi xue za zhi 01/2011; 91(4):239-42.
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Xin-Guang Liu,
Jin-Lin Li,
Ping Qin,
Juan Ren,
Shi-Hui Ma,
Lin Sun,
Yan Shi,
Xue-Bin Ji,
Yuan-Yuan Zhu,
Dao-Xin Ma,
Cheng-Shan Guo,
Xin Du,
Ming Hou, Jun Peng
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ABSTRACT: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by premature platelet destruction induced by autoantibodies directed against platelet glycoproteins (GPs). Despite being a clinically important disorder, ITP lacks a feasible diagnostic assay for routine clinical use. This study was meant to evaluate a newly developed flow cytometric immunobead assay for determination of platelet-bound GP-specific autoantibodies in comparison with indirect monoclonal antibody-specific immobilization of platelet antigen (MAIPA) in the diagnosis of ITP.
Platelet-bound and plasma GPIIb/IIIa and GPIb/IX autoantibodies were determined by flow cytometric immunobead assay and indirect modified MAIPA, respectively. The average fluorescence level for platelet-bound, GP-specific autoantibodies was given as a ratio to three normal controls tested simultaneously.
The median value of platelet-bound GPIIb/IIIa and GPIb/IX autoantibodies in ITP group were 3.09 (range 0.78, 30.2) and 3.09 (range 0.72, 19.2), respectively, which were significantly higher than non-ITP group [1.01 (0.67, 5.59) and 1.01 (0.79, 5.56), respectively, P<0.001] and normal controls [1.02 (0.72, 1.76) and 1.03 (0.79, 1.73), respectively, P<0.001]. The receiver-operating characteristics curve analysis showed an area under the curve of 0.895 for GPIIb/IIIa autoantibody and 0.859 for GPIb/IX autoantibody, respectively. Combined detection of GPIIb/IIIa or GPIb/IX autoantibodies by flow cytometric immunobead assay showed a sensitivity of 82.11% for ITP diagnosis.
This study demonstrated that determination of platelet-bound, GP-specific autoantibodies by flow cytometric immunobead assay was a convenient, sensitive, and specific test for the differential diagnosis of thrombocytopenic patients.
European Journal Of Haematology 01/2011; 86(4):339-46. · 2.61 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate the clinical significance of MAIPA test in diagnosis of idiopathic thrombocytopenic purpura (ITP) and in the differential diagnosis of antoimmune thrombocytopenias from nonimmune thrombocytopenias. METHODS: A total of 321 thrombocytopenic patients (118 males, 203 females) from 14 centers were studied. A modified monoclonal antibody immobilization of platelet antigen (MAIPA) method was used to detect the platelet glycoprotein-specific autoantibodies (anti-GP IIb/IIIa, anti-GPIb/IX) to double-blindly evaluate its sensitivity and specificity for the diagnosis of ITP and to investigate the impact of the antibodies on platelet count. RESULTS: The results showed that for the diagnosis of ITP, anti-GPIIb/IIIa, anti-GPIb/IX and both of them had the sensitivity of 39.75%, 32.64% and 55.23%; the specificity of 97.56%, 93.94% and 92.68%; the positive predictive value of 97.94%, 93.98% and 95.65%; the negative predictive value of 35.71%, 32.35% and 41.53%; and the total efficiency of 54.51%, 48.29% and 64.80%, respectively. The positivity of the autoantibodies in immune thrombocytopenias was incredibly higher than that in nonimmune thrombocytopenias. The platelet counts in the immune thrombocytopenias with autoantibody positivities were significantly lower than those without the autoantibodies. The platelet counts were negatively correlated with the concentration of the autoantibodies. The levels of anti-GPIIb/IIIa or anti-GPIb/IX or both of them dropped or disappeared in patients being responsive to steroid therapy. CONCLUSION: MAIPA assay is proved to be of great value for the diagnosis of ITP and for differential diagnosis of immune thrombocytopenias from nonimmune thrombocytopenias.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 09/2010; 31(9):581-585.
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ABSTRACT: To investigate the change of B-cell activating factor of the TNF family (BAFF) and regulatory T-cells (Tregs) before and after high-dose dexamethasone(HD-DXM) therapy and assess the effect of BAFF on Treg cells in immune thrombocytopenic purpura (ITP).
The plasma BAFF concentration was measured by ELISA, and Treg cell numbers by flow cytometry.
The plasma BAFF level \[(599.70 +/- 199.40) pg/ml\] was significantly increased (P < 0.05), and the percentage of Treg cells \[(1.56 +/- 0.73)%\] was significantly decreased (P < 0.01) in ITP patients before treatment as compared with that in controls \[(454.5 +/- 132.5) pg/ml and (4.08 +/- 1.08)%, respectively\]. After treatment with HD-DXM, the plasma BAFF level \[(296.9 +/- 119.7) pg/ml\] was significantly decreased (P < 0.01), and the percentage of Treg cells \[(5.94 +/- 2.22)%\] was significantly increased (P < 0.01). The BAFF level and Treg proportion had no significant correlation with platelets count (P > 0.05). In in vitro assays, no difference was found in the number of Treg cells between rhBAFF0 group and rhBAFF20 group \[(1.53 +/- 0.69)%, (1.49 +/- 0.67)%, P = 0.89)\].
BAFF level was increased and Treg cells decreased in ITP patients. HD-DXM might play a role in ITP treatment by down-regulating BAFF expression and up-regulating Treg cells number. BAFF had no influence on the number of Treg cells.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2010; 31(3):164-7.
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ABSTRACT: Interleukin-21 (IL-21) is critical in the development of autoimmune diseases. The role of IL-21 in the pathogenesis of immune thrombocytopenia (ITP) remains unknown.
We examined the expression of IL-21, IL-17, and interferon (IFN)-gamma in ITP patients and controls by enzyme-linked immunosorbent assay and flow cytometry. Detection of specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies was measured by modified monoclonal antibody specific immobilization of platelet antigens.
IL-21 was expressed on both CD3(+)CD8(-) T cells and CD3(+)CD8(+) T cells by flow cytometry. Plasma IL-21 level and the percentage of CD3(+)CD8(-)IL-21(+) T cells and CD3(+)CD8(+)IL-21(+) T cells were significantly elevated in ITP patients compared to controls. The percentage of CD3(+)CD8(-)IL-17(+) T (Th17), CD3(+)CD8(-)IFN-gamma(+) T (Th1), and CD3(+)CD8(+)IFN-gamma(+) T (Tc1) cells also significantly increased in ITP patients. Moreover, we found a significant positive correlation between CD3(+)CD8(-)IL-21(+) T cells and Th17 cells. In addition, a positive correlation between CD3(+)CD8(-)IL-21(+) T cells and Th1 cells was also found.
Together, our results indicated a possible role of IL-21 in ITP patients correlated to Th17 and Th1 cells, and blockade of IL-21 may be a reasonable therapeutic strategy for ITP especially those with active disease.
Journal of Clinical Immunology 12/2009; 30(2):253-9. · 3.08 Impact Factor
