-
[show abstract]
[hide abstract]
ABSTRACT: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by autoantibody-mediated platelet destruction. Multiple factors have been implicated in ITP pathogenesis, including T-lymphocyte dysfunctions. The protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene encodes lymphoid-specific phosphatase (LYP), a critical negative regulator of T cell activation. Single nucleotide polymorphisms (SNPs) of PTPN22 have been broadly associated with susceptibilities to various autoimmune disorders. Here we conducted a case-control study investigating whether the PTPN22 -1123G > C SNP contributes to the risk of ITP in Chinese population. The study included 191 ITP cases and 216 ethnically matched normal controls. Genotyping of -1123G > C SNP was performed using a single-base extension (SBE) and mass spectrometry method. Allelic and genotypic frequencies were compared between the case-control groups by the chi-square test. We observed significant overrepresentation of -1123G allele (p = 0.034, odds ratio (OR) = 1.374, 95% confidence interval (CI) [1.024-1.843]) and GG genotype (P = 0.038, OR = 1.951, 95% CI [1.031-3.694]) in the patients compared with the controls. Stratified analysis by gender and age of disease onset revealed comparable observations in both male and adult ITP cohorts. These data suggest a moderate association of PTPN22 -1123G > C SNP with susceptibility to ITP. Together with previous reports, our finding provides further evidence for PTPN22 being a general autoimmunity gene.
Platelets 10/2012; · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the efficacy of two different regimens of low doses rituximab for the treatment of adult patients with immune thrombocytopenia (ITP).
Fifty-one patients were enrolled in this study and was non-randomly assigned to receive 100 mg rituximab weekly for 4 weeks (group A, 31 cases) or a single dose of 375 mg/m2 rituximab (group B, 20 cases).
For group A: Overall and complete response (OR and CR) rates were 58% and 29% , respectively. In responders, the median time to response was 42 (10 -101) days, with a median follow-up time of 15 (10 - 16) months, 3 of 18 responders (17%) relapsed. For group B: OR and CR rates were 50% and 35% , respectively. In responders, the median time to response was 35 (18 - 108) days, with a median follow-up time of 13 (6 -17) months, 1 of 9 responders (11%) relapsed. No significant difference in the OR, CR, the relapse rate and relapse free survival was observed in patients between the two groups.
The low dose rituximab regimen (100 mg weekly for 4 weeks or a single close of 375 mg/m2) may be a useful alternative therapy in patients with ITP.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 09/2011; 32(9):583-6.
-
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 07/2011; 32(7):487-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Idiopathic thrombocytopenic purpura (ITP) is an acquired organ-specific autoimmune hemorrhagic disease with many immune dysfunctions. Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T-lymphocyte surface molecule that can down modulate and terminate immune responses. Recently, several studies have confirmed that some polymorphisms of this gene can influence its expression level, therefore speculating that they might be associated with autoimmune diseases. In order to investigate the role of the CTLA-4 gene in ITP, we investigated -318 and CT60 polymorphisms of the CTLA-4 gene in 186 ITP patients and 162 healthy controls through polymerase chain reaction (PCR)-restriction fragment length polymorphism. No significant differences were revealed in genotypes and allele distributions between the patients with ITP and the controls in both sites. Similar results were observed between the two groups when stratified by first onset age and disease course including acute childhood, chronic childhood, acute adult, and chronic adult. In the conclusion, these two single-nucleotide polymorphisms in CTLA-4 are not associated with susceptibility to ITP in a Chinese population.
Platelets 10/2010; 22(1):39-44. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hemophilia A (HA) is a common X-linked recessive bleeding disease caused by mutations in FVIII gene. The identification of mutation in HA subjects can lead to more accurate diagnosis and contribute to the genetic counseling/prenatal diagnosis.
Our objective is to identify the FVIII defects in 148 unrelated Chinese HA subjects and to analyze the potential consequence of novel mutations.
FVIII: C was assayed using one-stage method, and FVIII inhibitor was tested using Bethesda method. Intron 22 and 1 inversions were identified by PCR technique. Non-inversion mutations of FVIII gene were identified by direct sequencing. Novel mutations were further analyzed based on a B-domain deleted FVIII crystallographic structure and bioinformatics tools.
The intron 22 and 1 inversions affected 57 and three severe subjects, respectively. Sixty-seven different mutations were identified in non-inversion subjects including 35 novel mutations that were not reported previously. Novel mutations include five nonsense mutations, 15 missense mutations, three insertions, eight small deletions, two splice site mutations and two partial gene deletions. The potential deleterious effects of these novel missense mutations include disruption of the protein core, impairment of inter-domain interaction and FVIII binding with other proteins.
Similar to other races, intron 22 and one inversions are also recurrent mutation in severe HA subjects monitored in our centre. Sixty-seven mutations (52% novel reported) among 88 non-inversion subjects represent the high degree of heterogeneity of FVIII gene mutations causing HA. Characteristic of HA FVIII gene mutations extend our insight into structure-function relationship of the FVIII molecule.
European Journal Of Haematology 09/2010; 85(3):264-72. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pseudotumor is an uncommon but severe complication in patients with hemophilia. To our knowledge, although China has large population of persons with hemophilia, there is rare information on the incidence, clinical feature, image finding, and management of pseudotumor among Chinese patients. This study aimed at improving our knowledge on clinical diagnosis and management of hemophiliac pseudotumor. In this retrospective study, the medical records of 1248 patients with hemophilia diagnosed between January 1983 and October 2004 at our hospital were reviewed. The clinical feature, imaging finding, management, and outcome of 14 patients with pseudotumor among these patients with hemophilia were analyzed. All patients have hemophilia A (8 severe cases and 6 moderate cases). Eight patients sustained an injury prior to the development of pseudotumor. Main image findings included osteolysis lesion, soft tissue swelling, or lump. Surgical therapy was carried out in 7 patients and 6 achieved remission, with fistula formation remaining in 1. One patient underwent radiotherapy together with replacement therapy achieved remission. Three patients accepted replacement therapy as only management and only 1 patient achieved improvement of swelling. Our study showed that the incidence of pseudotumor in our enrolled patients with hemophilia is 1.12%. Hemophilic history of patients can contribute to the right diagnosis of pseudotumor. Surgical therapy together with sufficient replacement therapy is safe and effective.
Clinical and Applied Thrombosis/Hemostasis 06/2010; 17(3):279-82. · 1.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the effectiveness, safety as well as the immunological change (peripheral T cell subpopulation) in patients with idiopathic thrombocytopenic purpura (ITP) treated with lower dose rituximab.
Twenty-six patients with refractory ITP which were unresponsive to or relapse after steriod and IVIG treatment were treated with rituximab (100 mg per week for four weeks) and intravenous immunoglobulin (IVIG) treatment. Whole blood cell count, serum concentrations of IgG, IgM and IgA, platelet associated (PA)-IgG, PAIgA and PAIgM, peripheral T cell subpopulations, and B cells of CD19(+)/CD20(+) were detected before and after rituximab therapy.
Complete response (CR) was achieved in 6 patients (23.1%), response (R) in 10 (38.5%), and non-response (NR) in 10 (38.5%). One patient relapsed after R. The median follow-up time was 5.5 (0.8 - 8) months. The median response and CR time were 27 (1 - 104) and 41 (4 - 109) days, respectively. After the therapy, the serum concentrations of IgG, IgA, IgM, T cells of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD56(+), CD4(+)CD25(+) and CD4(+)CD25(+)FOXP3(+) were not changed, the number of CD4(+)CD25(+)FOXP3(-) T cells decreased (P < 0.05) and CD19(+)CD20(+) B cells significantly decreased (P < 0.01). PAIgG was lower after treatment compared with that before treatment (P < 0.05). There were no severe adverse effects during rituximab therapy.
Lower dose rituximab may be an effective and safe modality for patients with ITP.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2010; 31(3):161-3.
-
Dongsheng Gu,
Zhenping Chen,
Haifeng Zhao,
Weiting Du,
Feng Xue,
Jing Ge, Tao Sui,
Hao Wu,
Bin Liu,
Shihong Lu,
Lei Zhang,
Renchi Yang
[show abstract]
[hide abstract]
ABSTRACT: Immune thrombocytopenia (ITP) is an acquired organ-specific autoimmune disease with a polarization of T(h)1. Both the T(h)1 chemokine CXCL10 and T(h)2 chemokine CCL2 have been studied in several autoimmune diseases, but the status of these chemokines in ITP is still unknown. The aims of this study were to determine the expression of CXCL10 and CCL2 and their receptors, CXCR3 and CCR2, in ITP patients, and to conduct a preliminary study of the pathogenic roles of these factors in ITP. Plasma samples from 49 patients with ITP and 24 normal healthy subjects were assayed for CXCL10 and CCL2 plasma concentration by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction was performed to determine the mRNA expression of these chemokines and their receptors in the PBMNC of 24 normal controls and 28 active ITP patients as well as splenocytes of nine ITP patients. The CXCL10 levels in the plasma samples from patients with active ITP were significantly higher than those from healthy controls (p = 0.007) and decreased to normal levels in patients with remission ITP. In contrast, CCL2 levels were similar in patients with active disease, patients in remission, and control subjects. PBMNC of patients with active disease expressed more CXCL10 mRNA (p = 0.031) but less CCR2 mRNA (p = 0.005). Lower peripheral platelet count correlated with higher CXCL10 levels and CXCL10/CCL2 ratios. Our study demonstrated that plasma levels of CXCL10 and CXC10/CCL2 ratio were higher in patients with active ITP than in healthy donors, and had an association with platelet counts of the patients. CXCL10 might be a pathogenic factor of this disorder.
Human immunology 02/2010; 71(6):586-91. · 2.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epigenetics might contribute to autoimmune diseases including immune thrombocytopenic purpura (ITP). Methyl-CpG binding domain protein 4 (MBD4) plays an important role in DNA methylation and transcriptional regulation of gene expression. The polymorphism of the MBD4 gene may influence MBD4 activity on gene expression profiles, thereby influencing individual susceptibility to ITP. To verify this hypothesis, we investigated the association between the MBD4 polymorphism and the risk for ITP in the Chinese population. The polymorphism of MBD4 rs140693 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In this study, there was no significant difference in genotype and alleles distribution between the ITP patients and the controls. Similar results were observed between the two groups when stratified by age and disease course including acute childhood, chronic childhood, acute adult and chronic adult. In the conclusion, MBD4 polymorphism may not be a stratification marker to predict the susceptibility to ITP, at least in Chinese population.
Platelets 01/2010; 21(2):132-6. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Combined deficiency of factor V and VIII (F5F8D) is a rare, autosomal recessive disorder caused by mutations of either lman1 or mcfd2. To identify mutations of these two genes in a Chinese F5F8D family, the samples of peripheral blood were collected from the proband and her parents. Coagulation tests were carried out, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and coagulate activity of FV, FVIII (FV:C, FVIII:C). The genomic DNA was extracted, then all the exons and intron/exon boundaries of these two genes were amplified by polymerase chain reaction (PCR). The products were finally analyzed by direct sequencing. The results showed that the proband's APTT, PT, TT, Fg, FV:C and FVIII:C were 82.2 sec, 19.6 sec, 18.6 sec, 2.9 g/L, 7.1% and 18.7% respectively, while those parameters of the parents were all within the normal range. Two pathogenic mutations were identified in lman1 gene of the proband: one was the heterozygous c.912_913insA in exon 8 resulting in a frameshift of p.Glu305fsX20; the other was the heterozygous c.1366C > T in exon 11 resulting in p.Arg456X. The proband's father and mother were heterozygous for c.1366C > T and c.912_913insA respectively. It is concluded that F5F8D of the proband is caused by a novel compound heterozygous mutation of the lman1 gene, which has never been reported.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2010; 18(1):185-90.
-
[show abstract]
[hide abstract]
ABSTRACT: Epigenetics may influence the expression of numerous genes, which might contribute to autoimmune diseases. DNA methylation is mediated by DNA methyltransferases, especially DNA methyltransferase 3B (DNMT3B). Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between DNMT3B 579G>T and the risk for idiopathic thrombocytopenic purpura (ITP). The DNMT3B 579G>T polymorphisms were analyzed by PCR-RFLP. There was no significant difference in genotype and allele distribution between the ITP patient and the controls (p = 0.722 and 0.667, respectively). Similar results were observed between the 2 groups when stratified by age and disease course, including acute in childhood, chronic in childhood, acute in adult and chronic in adult. Importantly, this study showed a statistical difference in the distribution of SNP of DNMT3B between Chinese and Koreans or Americans. It is shown that the SNP of DNMT3B 579G>T may not be used on its own as a marker to predict the susceptibility to ITP in a Chinese population and that DNMT3B 579G>T promoter SNP varies from one ethnic population to another.
Acta Haematologica 08/2009; 122(1):31-5. · 1.35 Impact Factor
