Association of Interleukin-18 Gene Polymorphism with Severity of Chronic Immune Thrombocytopenia (ITP).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3693-3693
Author(s):  
Takayuki Saitoh ◽  
Norihiko Moriyama ◽  
Tomonori Takani ◽  
Takeki Mitsui ◽  
Takumi Hoshino ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Initial Diagnosis ◽  
Severe Thrombocytopenia ◽  
Interleukin 18 ◽  
Single Nucleotide ◽  
Chronic Itp ◽  
Significant Difference ◽  
Haplotype Frequencies ◽  
And Control

Abstract Abstract 3693 Introduction: Immune thrombocytopenia (ITP) is a chronic acquired organ-specific autoimmune disorder characterized by the production of antibodies against antigens on the membranes of platelets. Several cytokine studies have shown Th1 polarization in ITP patients. Interleukin-18 (IL-18) plays an important role in Th1 and Th2 immune response. Recent studies showed that single-nucleotide promoter polymorphisms influence the transcriptions of IL-18 mRNA. IL-18 polymorphism has been implicated in autoimmunity, including Crohn's disease, rheumatoid arthritis, and asthma. We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL-18 genes in patients with ITP, and analyzed the relationship between IL-18 SNPs and clinical features. Patients and Methods: One hundred patients (male/female; 22/78, median age; 54.5) diagnosed as chronic ITP and 151 healthy controls were included. Chronic ITP was defined as thrombocytopenia (platelet count < 100×109/L) persisting greater than 12 months, normal or increased marrow megakaryocytes, and no secondary immune or non-immune abnormality that could account for the thrombocytopenic state. ITP with severe thrombocytopenia was defined as thrombocytopenia (platelet count < 10×109/L) at presentation of ITP. The response criteria of the ITP International Working Group was used. A complete response (CR) is defined as any platelet count of at least 100×109/L, and a response (R) was defined as any platelet count between 30 and 100×109/L and at least doubling of the baseline count. Allparticipants gave written informed consent about the study. Genomic DNA was isolated from peripheral blood using the DNA Kit (QIAGEN, Hilden, Germany). An allele-specific polymerase chain reaction was used to analyze polymorphism in IL-18 –607A/C and -137G/C. Genotype and allele frequencies were compared between the study groups using Χ2-test. The characteristics and laboratory features of the ITP patients with each IL-10 promoter polymorphism were compared using X2-tests and student t-tests. Probability values <0.05 were considered statistically significant. Results: The platelet count was at an initial diagnosis ranged from 1×109/L to 98 ×109/L, with a median of platelet count of 15×109/L. Thirty-five patients (35%) had severe thrombocytopenia. Steroid treatment was given to 68 patients (68%), while splenectomy was used in 11 patients (11%).The frequencies of the genotypes were as follows: AA (34%), AC (57%), and CC (9%) for -607; GG (77%), GC (21%), and CC (2%) for -137 loci. The frequencies of each haplotype were as follows: C-G/C-G haplotype (9%), A-G/C-G haplotype (47%), A-C/C-G haplotype (10%), A-G/A-G haplotype (21%), A-G/A-C haplotype (11%) and A-C/A-C haplotype (2%). No significant differences in the genotype or haplotype frequencies demonstrated between chronic ITP patients and control group. However, patients with -137CC genotypes showed severe thrombocytopenia at initial diagnosis compared to those with -137GG/GC genotypes (5×109/L vs. 22×109/L, p=0.002). Furthermore, patients with A-C/A-C haplotype showed severe thrombocytopenic state (5×109/L vs. 22×109/L, p=0.002) compared to those without A-C/A-C haplotype. No significant difference of treatment response was observed according to IL-18 polymorphism. Conclusion: No significant differences in the genotype or haplotype frequencies demonstrated between chronic ITP patients and control. However, -137CC genotypes or AA/CC haplotype was associated with severity of chronic ITP. Our data suggest that the group with low IL-18 inducibility (i.e. -137CC genotype, A-C/A-C haplotype) may have more severe thrombocytopenia. Disclosures: No relevant conflicts of interest to declare.

The Influence of Polymorphisms of Interleukin-17F Genes on the Susceptibility and Clinical Significanse of Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3428-3428
Author(s):  
Takayuki Saitoh ◽  
Tetsuhiro Kasamatsu ◽  
Akihiko Yokohama ◽  
Hiroshi Handa ◽  
Norifumi Tsukamoto ◽  
...  
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Initial Diagnosis ◽  
Severe Thrombocytopenia ◽  
Single Nucleotide ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
And Control

Abstract Introduction: Recent several cytokine studies have shown Th1 polarization of the immune response in idiopathic thrombocytopenic purpura (ITP) patients. Interleukin-17 F(IL-17F) is a relatively new cytokine that regulates the adaptive and innate immune systems. In vivo studies in murine disease indicate that the Th17 lineage plays a pathogenic role in autoimmune disease. IL-17 polymorphism has been implicated in autoimmunity, including ulcerative colitis and asthma. Polymorphisms were studied, including the coding-region sequence variant single nucleotide polymorphism rs763780 (7488T/C), which causes a His-to-Arg substitution at amino acid 161 (H161R). We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL-17 genes in patients with ITP, and analyzed the relationship between IL-17 SNPs and clinical features. Patients and methods: Seventy-eight patients (male/female; 19/59, median age; 59.4) diagnosed as chronic ITP and 202 healthy controls were included. ITP with severe thrombocytopenia was defined as thrombocytopenia (platelet count < 10X109/L) at initial diagnosis of ITP. ALL patients gave written informed consent about the study. The platelet count was ranged from 1X109/L to 100X109/L at an initial diagnosis. Genomic DNA was isolated from peripheral blood using the DNA Kit (QIAGEN, Hilden, Germany). Genotyping in IL-17F was determined by PCR based technique. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of the ITP patients with each IL-10 promoter polymorphism were compared using χ2- tests and student t-tests. Probability values <0.05 were considered statistically significant. Results: The frequencies of the genotypes were as follows: TT (72%), TC (12%), and CC (16%). No significant differences in the genotype frequencies demonstrated between chronic ITP patients and control group. However, patients with TT/TC genotypes showed severe thrombocytopenic state at initial diagnosis compared to those with CC genotypes (42.2% vs. 23.1%, p<0.05). No significant difference was observed in treatment response according to IL-17 polymorphism. Conclusion: No significant differences in the genotype frequencies demonstrated between chronic ITP patients and control. However, homozygosity of the H161R variant was inversely associated with severity of chronic ITP. Thus, these findings suggest that IL-17 polymorphism reflect the severity of chronic ITP.

Interleukin-10 Gene Polymorphism Reflects the Severity of Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2111-2111
Author(s):  
Takayuki Saitoh ◽  
Tetsuhiro Kasamatsu ◽  
Madoka Inoue ◽  
W.H.S. Al-ma’Quol ◽  
Akihiko Yokohama ◽  
...  
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Response Rate ◽  
Initial Diagnosis ◽  
Control Group ◽  
Severe Thrombocytopenia ◽  
Bleeding Tendency ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Significant Difference

Abstract Introduction: Recent several cytokine studies have shown Th1 polarization of the immune response in Idiopathic thrombocytopenic purpura (ITP) patients. IL–10 is most important factor regulating Th1 and Th2 cytokine synthesis and IL–10 polymorphism has been implicated in autoimmunity and tumorigenesis. We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL–10 genes in patients with ITP, and analyzed the relationship between IL–10 SNPs and clinical features. Patients and methods: Seventy-eight patients (male/female; 19/59, median age; 59.4) diagnosed as chronic ITP and 202 healthy controls were included. ITP with severe thrombocytopenia was defined as thrombocytopenia (platelet count &lt; 10×109/L) at initial diagnosis of ITP. ALL patients gave written informed consent about the study. The platelet count was ranged from 1×109/L to 100×109/L at an initial diagnosis. In addition, 53 patients (67.9%) had bleeding tendency, and 20 patients (25.6%) had severe thrombocytopenia. Steroid treatment was given to 48 patients (61.5%), while splenectomy was applied to only 9 patients (11.5%). Genotyping in IL-10-1082G/A, -819C/T, −592A/C was determined by PCR based technique. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of the ITP patients with each IL-10 promoter polymorphism were compared using X2-tests and student t-tests. Probability values &lt;0.05 were considered statistically significant. Results: The frequencies of the genotypes were as follows: GG (0%), GA (6%), and AA (94%) for −1082; CC (12%), CT (51%), and TT (37%) for −812; CC (12%), CA (51%), and AA (37%) for −592 loci. The frequencies of each haplotype were as follows: ATA/ATA haplotype in 31 patients (40%), ATA/ACC haplotype in 35 patients (45%), ACC/ACC haplotype in 7 patients (9%). No significant differences in the genotype or haplotype frequencies demonstrated between chronic ITP patients and control group. However, patients with −592AA genotypes showed severe thrombocytopenic state at initial diagnosis compared to those with −592CA/CC genotypes (41.4% vs. 16.3%, p=0.01). Furthermore, patients with ATA/ATA haplotype showed severe thrombocytopenic state (38.7% vs. 17%, p=0.03) compared to those without ATA/ATA haplotype. In patients treated with steroids, the overall response rate was 71% with complete response rate of 23.2% and partial response rate of 47.8%. No significant difference was observed in treatment response according to IL-10 polymorphism. Conclusion: In previous investigations, −592AA genotype or ATA/ATA haplotype have been reported to be associated with the lower levels of IL-10 expression. Our data suggest that the group with low IL-10 inducibility (i.e. −592AA genotype, ATA/ATA haplotype) may have more severe thrombocytopenia compared to those with high IL-10 inducibility. It is also reported that low IL-10 inducibility type enhances Th1-type polarization in ITP. Furthermore, Panitsas et al. revealed that higher Th1/Th2 ratio in ITP patients correlate with lower platelet count. Thus, these findings suggest that IL-10 polymorphism reflect the severity of chronic ITP.

The Cytokine Polymorphisms Affect the Severity of Thrombocytopenia at Diagnosis in Chronic Immune Thrombocytopenia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2194-2194
Author(s):  
Takayuki Saitoh ◽  
Chiaki Ushie ◽  
Atsushi Iwasaki ◽  
Norihiko Moriyama ◽  
Tomonori Takani ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Platelet Count ◽  
Clinical Features ◽  
Immune Thrombocytopenia ◽  
Steroid Treatment ◽  
Severe Thrombocytopenia ◽  
Bleeding Tendency ◽  
Chain Reaction ◽  
Chronic Itp ◽  
Polymerase Chain

Abstract Abstract 2194 Introduction: The severity of immune thrombocytopenia (ITP) depends on the degree of the thrombocytopenia and the extent of bleeding. Some investigators have reported the association between the thrombocytopenia and cytokine dysregulation in ITP. We investigated the association between the severity of thrombocytopenia at diagnosis in ITP patients and several cytokine polymorphisms, including IL-10-1082A/G, -819T/C, -592A/C, IL-17F-7488T/C and IL-18-607A/C, −137G/C. Patients and methods: We examined 102 patients (male/female, 24/78; median age, 42) diagnosed with chronic ITP. The definition, response criteria, including complete response (CR)and response (R), loss of CR,and “corticosteroid-dependence” were assessed according to the criteria of the ITP International Working Group. ITP with severe thrombocytopenia (ST group)was defined as thrombocytopenia (platelet count < 10×109/L) at the initial diagnosis of ITP. Genotyping of IL-10 (rs1800870 − 1082 A/G, rs1800871 − 819 T/C, and rs1800872 − 592 A/C) and IL-17F (rs763780, 7488 T/C) polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the genotyping of the IL-18 polymorphism (rs187238 −137G/C and rs1946518−607 A/C) was determined by the allelic specific polymerase chain reaction technique. To confirm the accuracy of the assay, amplification products of several individuals were sequenced using an ABI Prism Genetic Analyzer. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of ITP patients with each polymorphisms were compared using χ2-tests and student t-tests. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated for each study. All patients were provided written information about the study. This study was approved by the Institutional Research Board of Gunma University Hospital. Results: Clinical features of chronic ITP: The platelet count ranged from 1×109/L to 98×109/L with a mean of platelet count of 32×109/L at the initial diagnosis. Fifty seven patients (49%) had bleeding tendency. Steroid treatment was given to 68 patients (66.7%) and eradication of Helicobacter pylori (H. pylori) was performed in 32 patients (31.4%), while splenectomy was performed in only 11 patients (10.8%). Clinical features of ST group vs. non-ST group in chronic ITP: Of these 102 patients, 17 (16.7%) had severe thrombocytopenia (platelet count < 10×109/L) (ST group). ST group were significantly older (ST group: median 59 years vs. non-ST group: 41 years, p<0.01) and had more severe bleeding tendency (ST group: 100% vs. non-ST group: 54%, p<0.0001). Steroid treatment was frequently given to ST group than to non-ST group (ST group: 100% vs. non-ST group: 59.5%, p<0.001). Though the response to corticosteroids treatment was not significantly different between ST group and non-ST group (CR rate, ST group: 50% vs. non-ST group: 51.0%, p=0.94), corticosteroid-dependent patients in ST group was significantly higher than in non-ST group (76.9% vs. 25.3%, p<0.005). Polymorphism study of ST group vs. non-ST group in chronic ITP: The frequencies of genotypes of cytokines in patients with chronic ITP according to the definition of criteria of ST were as follows: AA (93.3% vs. 97.1%) and AG (6.7% vs. 2.9%, p=0.48) for IL-10–1082; TT (46.7% vs. 33.3%), TC (33.3% vs.55 %) and CC (20% vs. 11.7%) for IL-10–819; AA (46.7% vs. 33.3%), AC (33.3% vs.55 %) and CC (12.2% vs. 11.5%) for IL-10–592; TT (100% vs. 81%) and TC (0% vs. 19%) for IL-17F; GG (82.4% vs. 74.4%), GC (17.6% vs. 23.2%) and CC (0% vs. 2.4%) for IL-18–137; AA (35.3% vs. 34.1%), AC (58.8% vs. 53.7%) and CC (5.9% vs 12.2%) for IL-18–607 loci (ST group vs. non-ST group, respectively). No significant difference was observed between ST group and non-ST group according to IL-10–1082A/G, −819T/C, −592A/C, and IL-18–607A/C, −137G/C polymorphism. However, the numbers of IL-17F 7488TT genotype (higher function type) in ST group were significantly higher than in non-ST group (ST group: 100% vs. non-ST group: 81% p<0.05). Conclusion: These findings suggest that severe thrombocytopenia at diagnosis have an impact of bleeding tendency and corticosteroid-dependency of chronic ITP. Furthermore, IL-17F polymorphism may affect the severity of thrombocytopenia of chronic ITP. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic evaluation of immune thrombocytopenia outcomes in Egyptian children: a retrospective single-center experience

2021 ◽  
Vol 20 (3) ◽  
pp. 26-30
Author(s):  
Aliaa Mohammed Diab ◽  
AlRawhaa Ahmed Abouamer ◽  
Ghada Saad Abdel Motaleb ◽  
Khaled Abdelaziem Eid ◽  
Heba Ismaiel Abdelnaiem
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Laboratory Data ◽  
Lactate Dehydrogenase Level ◽  
Female Gender ◽  
University Hospitals ◽  
Female Ratio ◽  
Chronic Itp ◽  
Egyptian Children ◽  
Significant Difference

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children. This retrospective study was designed to analyze presenting features of ITP cases in Benha, evaluate outcomes in children and determine prognostic factors. This research was accepted by Research Ethics Committee (REC) of Faculty of Medicine, Benha University (chairman: Prof. Nermeen Adly Mahmoud). Ethics comittee refrence number MS 40-3/2019. Records of 308 children with ITP in Benha University Hospitals and Benha Children Hospital haematology clinics between May 2014 and January 2021 were retrospectively analyzed. Socio-demographic, clinical, and laboratory data of the studied children such as age, gender, the type of residence, the date of diagnosis, complaints at presentation, preceding vaccination or infection, the type of bleeding, initial platelet count, LDH (lactate dehydrogenase) level, initial treatment, and outcomes were recorded. A total of 308 children diagnosed with ITP were included, clinical courses were determined as newly diagnosed and chronic in 71.4% and 28.6%, respectively. The median age of patients at diagnosis was 5 ± 3.4 years. The male/female ratio was 1.14. The median age at diagnosis was significantly higher in chronic ITP patients (p < 0.001); patients ≥ 10 years were more likely to develop chronic ITP than younger ones (p = 0.029). Regarding residency, seasonality, type of bleeding and history of preceding infection or vaccination, the difference was not statistically significant. Initial platelet counts > 20 × 109 were significantly more prevalent in chronic ITP (p < 0.001). LDH level at presentation was significantly higher in chronic cases (p = 0.046). Initial lines of treatment were the following: steroids, IVIG, and IVIG with steroids (in 88%, 5.2%, and 2.9% of the cases, respectively). A total of 3.9% of the children did not receive any treatment. There was no significant difference in the outcomes between the initial lines of treatment (p = 0.105). In our study, age > 10 years, female gender, higher platelet count and high LDH level at presentation were found to increase the probability of chronic ITP.

scholarly journals A Comparative Prospective Observational Study of Children and Adults with Immune Thrombocytopenia: 2-Year Follow-up

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3741-3741 ◽  
Author(s):  
Thomas Kuehne ◽  
Alexandra Schifferli
Keyword(s):  
Platelet Count ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Initial Diagnosis ◽  
Diagnostic Methods ◽  
Newly Diagnosed ◽  
Time Points ◽  
Platelet Counts ◽  
Chronic Itp

Abstract Introduction It is widely accepted that immune thrombocytopenia (ITP) of children differs from that of adults in the clinical course, such as the rate of spontaneous remission, the bleeding risk and the need of treatment. However, this assumption is limited by incongruity of study populations and divergences of collected information, definitions, study objectives and end-points. Surprisingly, data of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) at initial diagnosis demonstrated far less differences in clinical and laboratory findings between children and adults than expected (Kühne et al. Haematologica 2011). This suggests that newly diagnosed ITP may be driven by similar pathophysiological mechanisms. Differences may occur in the ability of restoring tolerance. We analyzed 6-, 12-, and 24-month follow-up data of children and adults recorded in the PARC-ITP Registry. Design and Methods PARC-ITP is an international multi-center registry designed to collect data prospectively of children and adults with newly diagnosed ITP, and was opened in May 2004. Demographic information, diagnostic methods, clinical data, and efficacy and safety of management are continuously registered at the time of diagnosis, 6 and 12months and then yearly. Patients younger than 3 months (n=167) and those with a platelet count of >100x109/l were excluded from the analysis. Patients with missing follow-up data at certain time-points were not excluded. Remission of ITP was defined as a platelet count of >100x109/l at any time point and regardless of therapy. Platelet counts of chronic ITP were defined as being <100x109/l at 12 or 24 months. The data were analyzed with descriptive statistics. Results A total of 3'780 evaluable patients with the initial diagnosis of primary ITP were recorded in the PARC-ITP database between 2004 and 2015. There were 3360 children (3 months - 16 years) and 420 adults (≥16 years). The pediatric female: male ratio was 1:1.09, and that of adults was 1:0.54. Follow-up information was available for 67% of children at the 6-month, 49% at the 12-month and 31 % at the 24-month evaluation and in adults in 77%, 64%, and 47%, respectively. In children remission was seen at 6, 12 and 24 months in 70%, 70%, and 71%, and in adults in 45%, 49%, and 56%, respectively. Of the patients with a platelet count of <100x109/l at 6 months, 212/590 children (36%) and 42/152 adults (28%) achieved again a remission at 12-months. The platelet counts of children and adults with chronic ITP at 12 months were 46±30x109/l and 51 ±26x109/l. Adults with a diagnosis of chronic ITP at 12 and 24 months reported having no bleeding in 69% and 65% for the last follow-up period, children in 37% at both time-points. Children with thrombocytopenia at 6, 12 and 24-months received platelet-enhancing drugs in 58%, 46% and 47% and adults in 58%, 52% and 40%, respectively. The diagnosis of secondary ITP and other causes of thrombocytopenia was reported for 123 children, i.e. 3.5%, 1.9% and 1.3% at 6, 12 and 24 months, respectively and 21 adults, i.e. 3.7%, 2.3% and 1.7% at 6, 12 and 24 months, respectively. The reported cause was an infectious disease in both children (49%) and adults (52%). Discussion The PARC-ITP Registry is the first cohort of ITP patients including a mixed pediatric and adult population. Limitations include the variety of participating centers (n=74), data registration on a voluntary basis, a high percentage of loss of follow-up and an unbalanced number of children and adults. Preliminary analyses of follow-up data demonstrate similarities between children and adults in much more areas, than previously assumed. Differences in remission rates where confirmed but in a smaller extent than expected. Treatment requirement in patients with active disease was very similar in both age groups. Surprisingly, adults with a diagnosis of chronic disease exhibited a greater number of a non-bleeding phenotype than children. Conclusion Understanding differences or similarities among children and adults with ITP may guide in finding immune modulatory strategies with the goal of achieving early sustained responses. Disclosures Kuehne: Amgen: Research Funding; UCB Biosciences GmbH: Consultancy. Schifferli:Amgen: Research Funding.

Efficacy Of Helicobacter Pylori Eradication For The First Line Treatment Of Immune Thrombocytopenia Patients With Moderate Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2324-2324
Author(s):  
Hyo Jung Kim ◽  
Won Sik Lee ◽  
Hawk Kim ◽  
Jung-Hee Lee ◽  
Sang Min Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Base Line ◽  
Line Treatment ◽  
First Line ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Significant Difference ◽  
H Pylori ◽  
First Line Treatment

Abstract Background Since the first case report of Gimaz et al., several investigators have reported that the secondary immune thrombocytopenia (ITP) can occur in patients with Helicobactor pylori (H. pylori) infection. Eradication of H. pylori has been shown to result in improvement in thrombocytopenia. In one systematic review of 696 patients with H. pylori infection it showed 50.3% overall response (platelet count >= 30 X 109/L and at least a doubling of the base line count) after H. pylori eradication. Under these results, ASH 2011 guidelines for ITP recommended that eradication therapy be administered in adult patients who are found to have H. pylori infection (grade 1b). But also they recommended that treatment be administered for newly diagnosed patients with a platelet count < 30 X 109/L. To the best of our knowledge, there was no prospective study to evaluate the efficacy of H. pylori eradication for ITP patient with moderate thrombocytopenia and positive H. pylori. In Korea, the prevalence of H. pylori was reported as high as 60 – 65% in general adult population. The response rate and price of 1st line triple regimen for H. pylori eradication were known to be 70 - 80% and around 100 US dollars in Korea. With these circumstances, tolerable treatment like H. pylori eradication for ITP patients with platelet count >=30 X 109/L is challengeable. Thus, we performed the prospective multicenter phase II study to evaluate the efficacy of H. pylori eradication for the 1st line treatment of persistent or chronic ITP patients with moderate thrombocytopenia. Methods We enrolled patients with persistent (3 to 12 months from diagnosis) or chronic (lasting for more than 12 months) ITP defined by international working group. The platelet counts of patients were between 30 X 109/L and 70 X 109/L. And all patients had positive result of C13-urea breath test (UBT) and had never been treated for ITP or H. pylori. Patients with other secondary ITP could not be enrolled. Patients received lansoprazole 30mg twice daily, amoxicillin 1000mg twice daily and clarithromycin 500mg, twice daily for one week. Eradication of H. pylori was evaluated at eighth week after treatment by UBT. Platelet counts were monitored at 2 weeks and after then at every month for a year. Complete response (CR) was defined as a platelet count >= 100 X 109/L. Partial response (PR) was defined as a platelet increase of >= 30 X 109/L and at least a doubling of the base line count. The primary endpoint was CR rate at 3 months after treatment. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT01255332). Results Twenty-six patients were enrolled between November 2010 and May 2013 from 6 medical centers in Korea. Two patients with HCV infection and one patient with more than 70 X 109/L of platelet counts were excluded from analysis. The mean initial platelet counts of 23 patients (7 males, 16 females, median age 43 years and range 19 - 58 years) was 52.7 ± 9.5 X 109/L (range 39 – 68 X 109/L). All patients except one checked UBT after treatment and H. pylori eradication was achieved in 86.3% (19/22) of patients. CR was obtained in 13 of 23 patients (56.5%) within 3 months after treatment. And no PR was found until this time point. The median time to CR after initiating treatment was 4 weeks (range 2 – 8 weeks). CR rate of the patients who achieved H. pylori eradication was 63.2% (12/19). Unlike other reports, there was no significant difference on initial platelet counts among CR group and non-responder group and no significant correlation on the platelet levels between baseline and initial 3 months (Fig 1). Only 2 of 26 patients could not continue medication due to nausea and diarrhea, respectively. There was no other significant adverse event. Conclusion The eradication of H. pylori is an effective first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high CR rate and rapid onset. And it has acceptable toxicity and relatively low cost. This study supports routine detection and eradication of H. pylori infection in ITP patients especially in populations with a high prevalence of this infection. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Investigation of TAGAP gene polymorphism (rs1738074) in Turkish pediatric celiac patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Melek Pehlivan ◽  
Tülay K. Ayna ◽  
Maşallah Baran ◽  
Mustafa Soyöz ◽  
Aslı Ö. Koçyiğit ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Disease Risk ◽  
Polymerase Chain Reaction Method ◽  
Control Group ◽  
Healthy Children ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Allele Specific ◽  
And Control

Abstract Objectives There are several hypotheses on the effects of the rs1738074 T/C single nucleotide polymorphism in the TAGAP gene; however, there has been no study on Turkish pediatric patients. We aimed to investigate the association of celiac disease (CD) and type 1 diabetes mellitus (T1DM) comorbidity with the polymorphism in the TAGAP gene of Turkish pediatric patients. Methods Totally, 127 pediatric CD patients and 100 healthy children were included. We determined the polymorphism by the allele-specific polymerase chain reaction method. We used IBM SPSS Statistics version 25.0 and Arlequin 3.5.2 for the statistical analyses. The authors have no conflict of interest. Results It was determined that 72% (n=154) of only CD patients had C allele, whereas 28% (n=60) had T allele. Of the patients with celiac and T1DM, 42.5% (n=17) and 57.5% (n=23) had T and C alleles, respectively. Of the individuals in control group, 67% (n=134) had C allele, whereas 33% (n=66) had T allele. Conclusions There was no significant difference in the genotype and allele frequencies between the patient and control groups (p>0.05). There was no significant association between the disease risk and the polymorphism in our study group.

scholarly journals Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 177-185 ◽  
Author(s):  
L Corash ◽  
HY Chen ◽  
J Levin ◽  
G Baker ◽  
H Lu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Temporal Relationship ◽  
Recovery Phase ◽  
Severe Thrombocytopenia ◽  
Detectable Change ◽  
Platelet Volume ◽  
Murine Bone Marrow ◽  
Ploidy Class

Abstract We have established a murine model and techniques with which to serially study thrombocytopoiesis after induction of experimental immune thrombocytopenia of variable severity and duration. Bone marrow megakaryocyte ploidy distribution was determined by using unfractionated bone marrow, a polyclonal megakaryocyte-specific probe, and two-color, fluorescence-activated flow cytometry. With these techniques, the modal megakaryocyte ploidy class in normal murine bone marrow was 16N. Serial studies of bone marrow megakaryocyte ploidy after the induction of acute, severe thrombocytopenia (platelet count, less than 0.05 X 10(6) microL) demonstrated no detectable change in the ploidy distribution at 12, 24, and 36 hours after the onset of thrombocytopenia. At 48 hours, the modal ploidy class shifted from 16N to 32N, and the 64N class increased significantly (P less than .001). The ploidy distribution returned to normal 120 hours after the onset of thrombocytopenia. A lesser degree of thrombocytopenia (platelet count reduction to 0.100 to 0.200 X 10(6)/microL) delayed the modal ploidy class shift from 16N to 32N until 72 hours after the onset of thrombocytopenia. Chronic, severe thrombocytopenia (platelet count, less than 0.05 X 10(6)/microL for seven days) resulted in a modal ploidy class shift from 16N to 32N during the thrombocytopenic phase and an enhanced increase in the 64N megakaryocyte class during the recovery phase. Mean platelet volume (MPV) was simultaneously measured on isolated total platelet populations after induction of thrombocytopenia. MPV was significantly increased (P less than .001) as early as eight hours after the onset of acute, severe thrombocytopenia, 40 hours before a shift in the ploidy distribution. Mild thrombocytopenia (platelet count reduction to 0.400 X 10(6)/microL) was not associated with a ploidy shift but did result in a significantly increased MPV (P less than .001). These studies demonstrate that the temporal relationship and magnitude of the effects of thrombocytopenia upon megakaryocyte ploidy distribution are dependent upon the degree and the duration of the thrombocytopenic stimulus and that the effects of experimental thrombocytopenia on platelet volume and megakaryocyte ploidy are dissociated.

scholarly journals Association of rs780094 polymorphism of glucokinase regulatory protein with non-alcoholic fatty liver disease

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Saba Mohammadi ◽  
Safar Farajnia ◽  
Masoud Shadmand ◽  
Fatemeh Mohseni ◽  
Roghayyeh Baghban
Keyword(s):  
Regulatory Protein ◽  
Single Nucleotide ◽  
Alcoholic Fatty Liver ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Study Population ◽  
Northwest Of Iran ◽  
And Control ◽  
The Relationship ◽  
Tabriz City

Abstract Objective GCK rs780094 polymorphism is a single nucleotide polymorphism that has been associated with obesity, type II diabetes and dyslipidemia in some populations, conditions that highly related to NAFL etiology. The present study aimed to evaluate the relationship between NAFLD and rs780094 polymorphism in patients with NAFLD in Tabriz city, northwest of Iran. The rs780094 polymorphism was determined in 74 patients with NAFLD by PCR–RFLP technique. Demographic information was collected using a questionnaire and biochemical analysis was performed using standard laboratory methods. Results There was a significant difference between case and control subjects for alanine aminotransferase, aspartate aminotransferase, HDL-C and triglycerides (P < 0.05). Analysis by PCR–RFLP method revealed that there were no significant differences between NAFLD and healthy subjects for rs780094 polymorphism in the study population. The results of this study indicated that rs780094 polymorphism is not associated with NAFLD in subjects from Tabriz city.

Interferon Gamma +874A/T Polymorphism in Children with Idiopathic Thrombocytopenic Purpura

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4539-4539
Author(s):  
Fatih Demircioglu ◽  
Hale Ören ◽  
Sefa Kizildag ◽  
Sebnem Yilmaz ◽  
Berna Atabay ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Interferon Gamma ◽  
Gene Polymorphisms ◽  
Statistical Difference ◽  
Control Group ◽  
Blood Samples ◽  
Chronic Itp ◽  
Significant Difference ◽  
Acute Itp ◽  
And Control

Abstract A recent study showed that expression of Toll-like receptor and interferon-gamma associated genes is significantly increased in patients with chronic ITP. Interferon-gamma is an important protein which takes place in immunoregulation. +874A/T polymorphism in the first introne of interferon gamma gene is found to be associated with the development and clinical phenotype of some autoimmune diseases such as diabetes mellitus, thyroiditis, multiple sclerosis, and SLE. The aim of our study was to investigate whether interferon gamma +874A/T polymorphism is a risk factor for the development of ITP and whether it affects the clinical course and response to the treatment. Thirty five children with acute ITP and 40 children with chronic ITP who were followed for at least 6 months were included. Control group consisted 90 healthy children. Two millilitres of blood sample was taken into sterile tubes containing 0.1% EDTA from each child and all blood samples were stored at −20 until analysis. DNA was isolated from blood samples and interferon gamma +874A/T polymorphism was studied with real-time PCR and LightCycler TM. Twenty one patients had AA, 35 patients had AT, and 19 patients had TT genotype. In the control group, 47 children had AA, 36 children had AT, and 7 children had TT genotype. There was a statistical difference between ITP and control group regarding the genotype (p=0.001). The frequency of A and T alleles in ITP group was 52% and 48%, respectively. The frequency of A and T alleles in control group was 72.7% and 27.8%, respectively. The frequency of allele distribution was statistically different between the ITP and control groups (p&lt;0.0001). There was a statistical significant difference between acute ITP and control group regarding the frequency of AA, AT, and TT gene polymorphisms and allele frequency (p=0.002, p=0.002). Similarly, there was a statistical significant difference between chronic ITP and control group regarding the frequency of AA, AT, and TT gene polymorphisms and allele frequency (p=0.008, p=0.002). The frequency of AA, AT, and TT gene polymorphisms and allele frequency showed no statistical difference between acute and chronic ITP groups (p=0.285, p=0.896). There was no correlation between interferon gamma +874A/T polymorphism and severity of bleeding (mild, moderate and severe) (p=0.09). There was no correlation between interferon gamma +874A/T polymorphism and response to long term treatment in patients with chronic ITP (p=0.568). In conclusion, there was a significant difference between patients with ITP and children in control group regarding interferon gamma +874A/T polymorphism and in the light of recent data involving other autoimmune disorders, we think that interferon gamma +874A/T polymorphism may be a risk factor for ITP.

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