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 ◽  
...  

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.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3693-3693
Author(s):  
Takayuki Saitoh ◽  
Norihiko Moriyama ◽  
Tomonori Takani ◽  
Takeki Mitsui ◽  
Takumi Hoshino ◽  
...  

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.


2021 ◽  
Author(s):  
Qiong Wu ◽  
Yu-Lin Zhou ◽  
Hui Kong ◽  
Yun-Sheng GE ◽  
Yan-Yan Shen ◽  
...  

Abstract Background Individuals with rare cytogenetic variants have contributed to our understanding of the genetics of sex chromosome and its disorders. Here, we report on a 23 years old man with a de novo 47,XX,+mar.ish der(Y)neo(Y)(pter-->p11.2::q11.23-->neo-->q11.23-->qter)(DYZ3-,SRY+,WCPY+) chromosome complement, accompanying with azoospermia and some of other clinical features suggestive of Klinefelter's Syndrome. The constitution of the patient was verified by GTG-banding, QFQ-banding, Fluorescence in Situ Hybridization and Polymerase Chain Reaction. Accordingly, we report the finding of a structurally abnormal chromosome Y with no detectable DYZ3 centromeric sequence and with no detection of AZF a, AZF b and AZF c, with clinical features suggestive of Klinefelter's Syndrome. This is the first reported case of Klinefelter's Syndrome involving a neocentromic Y among previously described cases with a neocentromere. Case presentation we report on a 23 years old man with a de novo 47,XX,+mar.ish der(Y)neo(Y)(pter-->p11.2::q11.23-->neo-->q11.23-->qter)(DYZ3-,SRY+,WCPY+) chromosome complement, accompanying with azoospermia and some of other clinical features suggestive of Klinefelter's Syndrome. The constitution of the patient was verified by GTG-banding, QFQ-banding, Fluorescence in Situ Hybridization FISH and Polymerase Chain Reaction PCR. Conclusions It can be inferred that a neocentromic Y is formed by identification of FISH, PCR and the fact that this markerof Y chromosome is present in 100% of peripheral blood cells and has been efficiently retained through cell divisions despite the absence of the endogenous cen­tromere region. To our knowledge, this is the first reported case of Klinefelter's Syndrome involving a neocentromic Y among previously described cases with a neocentromere, which adds to the catalog of chromosomal aberrations. The present study not only improves the understanding of karyotype/phenotype relationships between neocentric marker Y chromosomes and KFS male infertility, but also supports the hypothesis that the combined application of molecular cytogenetic analysis might help to identify breakpoints, origins, and the constitution of the marker chromosomes.


2021 ◽  
Vol 2 (1) ◽  
pp. 15-20
Author(s):  
Li Xu ◽  

We report the laboratory results of conjunctival RT-PCR tests and some clinical features of these patients infected with COVID 19 in Shenyang, China


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Mingkwan Lumyongsatien ◽  
Pimkwan Jaru-ampornpan ◽  
Mongkol Uiprasertkul ◽  
Dinesh Selva

Orbital mucormycosis caused by Saksenaea vasiformis is extremely rare. Herein, we report an immunocompetent 22-year-old Thai female who presented with two months of progressive right upper eyelid mass, associated with swelling, redness, and ptosis. She failed to improve despite multiple courses of antibiotic and steroid treatment. Computed tomography (CT) scan showed infiltration involving the upper eyelid and lacrimal gland. Fungal hyphae were revealed by histopathological study. Polymerase chain reaction (PCR) was positive for Saksenaea vasiformis (GenBank: accession number FR687327.1). The patient was successfully treated with surgical debridement, amphotericin B, and oral posaconazole.


2012 ◽  
Vol 94 (6) ◽  
pp. 596-602 ◽  
Author(s):  
Niels V. Rekers ◽  
Ingeborg M. Bajema ◽  
Marko J.K. Mallat ◽  
Kim Zuidwijk ◽  
Jacqueline D.H. Anholts ◽  
...  

2019 ◽  
Author(s):  
Yu-Ting Hsiao ◽  
Ming-Tse Kuo ◽  
Wei-Yu Chiang ◽  
Tsai-Ling Chao ◽  
Hsi-Kung Kuo

Abstract Background To report the epidemiology and clinical features of viral anterior uveitis in patients in southern Taiwan. Methods A retrospective, case series study. HLA-B27 negative anterior uveitis patients with increased intraocular pressure or corneal edema seen at Kaohsiung Chang Gung Memorial Hospital from January 1, 2007 to January 31, 2018 had their aqueous sent for polymerase chain reaction analysis. Their records were reviewed for demographic data, ocular findings, and laboratory results. Results In the aqueous samples obtained from 102 eligible eyes, 42 eyes were herpesviridae-positive, which included 9 with herpes simplex virus (8.8%), 5 with varicella-zoster virus (4.9%), 27 with cytomegalovirus (26.5%), and 1 with Epstein-Barr virus (1%). Herpesviridae-positive patients were more likely to be male, and have glaucoma. Glaucoma and pseudophakic eyes were significantly associated with CMV-positive eyes. Conclusion PCR analysis of the anterior chamber fluid is important for the confirmation of the diagnosis of viral anterior uveitis. Cytomegalovirus anterior uveitis is not uncommon in patients in southern Taiwan, and it may follow an uneventful cataract extraction in immunocompetent patients.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2111-2111
Author(s):  
Takayuki Saitoh ◽  
Tetsuhiro Kasamatsu ◽  
Madoka Inoue ◽  
W.H.S. Al-ma’Quol ◽  
Akihiko Yokohama ◽  
...  

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.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3739-3739
Author(s):  
Yuya Kitamura ◽  
Takayuki Saitoh ◽  
Rumi Ino ◽  
Kazuki Honma ◽  
Tomomi Nagashima ◽  
...  

Abstract [Introduction] Immune thrombocytopenia (ITP) is an autoimmune disorder showing T helper type1 (Th1) cytokine polarization. Second-line treatment for ITP is generally used for patients with persistent thrombocytopenia and bleeding tendency after steroid treatment. We have recently shown Th1/Th2 cytokine polymorphisms affect the risk of chronic ITP. However, no previous study has demonstrated the association between Th1/Th2 cytokine polymorphisms and treatment response for chronic ITP. We explored the influence of Th1/Th2 cytokine polymorphisms to the clinical features and treatment response in patients with chronic ITP. [Patients and Methods] The present study included 126 Japanese patients (92 female and 34 male, median age: 47.7, range: 2.4-82.3 years) diagnosed with chronic ITP according to the criteria of ITP International Working Group. The patient characteristics were summarized in Table1. We examined Th1/Th2 cytokine polymorphisms: INF-g +874T/A, INF-gR -611G/A, IL-4 -590C/T, IL-4Ra Q576R, IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E using by PCR based method and direct sequencing. Clinical characteristics, including age, gender, platelet number, bleeding tendency, treatment response were also investigated. Second-line treatment was defined as additional therapy after steroid treatment. This study was approved by the Institutional Review Board of Gunma University Hospital. [Results] We divided chronic ITP patients (n=126) into 2 groups: the patients who received second-line treatment (SL group, n=36) and the patients who did not receive second-line treatment (non-SL group, n=90). In SL-group, the splenectomy was performed in 19 patients (51.4%) and thrombopoietin receptor agonists were given in only 7 patients (19.4%). The clinical characteristics and Th1/Th2 cytokine genotype frequencies of SL group and non-SL group were shown in Table1. The patients in SL group showed severer thrombocytopenia at diagnosis (SL group: median 12.0~109/L vs. non-SL group: median 31.0~109/L, p value=0.001). However, no significant difference was observed between SL group and non-SL group in gender, age, or bleeding tendency. As compared to non-SL group, SL group had significantly higher frequencies of IL-4 -590 CC genotype (low expression type) (SL group: 25.0% vs. non-SL group: 8.9%, p=0.02) and IL-10RB K47E non-EE genotype (low expression type) (SL group: 86.1% vs. non-SL group: 66.7%, p=0.03). Multivariate analysis of requirement for second-line treatment showed an independent significance of IL-4 -590C/T CC genotype (p=0.01) and severe thrombocytopenia (p<0.05). Furthermore, IL-10RB K47E non-EE genotype was associated with thrombocytopenia during the clinical course and requirement for second-line treatments in all patients with ITP. [Conclusion] Our data suggest that Th2 cytokine polymorphisms, IL-4 -590 CC genotype and IL-10RB K47E, increase the requirement of second-line treatment for chronic ITP. Disclosures No relevant conflicts of interest to declare.


2010 ◽  
Vol 55 (1) ◽  
Author(s):  
Anupkumar Anvikar ◽  
Dinesh Singh ◽  
Ruchi Singh ◽  
Aditya Dash ◽  
Neena Valecha

AbstractA patient was admitted with fever, vomiting, restlessness and convulsions. He was febrile and unconscious. Laboratory tests showed a low platelet count and ruled out enteric fever and dengue. His peripheral blood smear was positive for Plasmodium vivax. The presence of P. vivax monoinfection was confirmed by polymerase chain reaction and DNA sequencing. The report highlights the importance of considering the possibility of complications even in P. vivax malaria and formulation of strategies accordingly.


2019 ◽  
Author(s):  
Yu-Ting Hsiao ◽  
Ming-Tse Kuo ◽  
Wei-Yu Chiang ◽  
Tsai-Ling Chao ◽  
Hsi-Kung Kuo

Abstract Background To report the epidemiology and clinical features of viral anterior uveitis in patients in southern Taiwan. Methods A retrospective, case series study. HLA-B27 negative anterior uveitis patients with increased intraocular pressure or corneal edema seen at Kaohsiung Chang Gung Memorial Hospital from January 1, 2007 to January 31, 2018 had their aqueous sent for polymerase chain reaction analysis. Their records were reviewed for demographic data, ocular findings, and laboratory results. Results In the aqueous samples obtained from 102 eligible eyes, 42 eyes were herpesviridae-positive, which included 9 with herpes simplex virus (8.8%), 5 with varicella-zoster virus (4.9%), 27 with cytomegalovirus (26.5%), and 1 with Epstein-Barr virus (1%). Herpesviridae-positive patients were more likely to be male, and have glaucoma. Glaucoma and pseudophakic eyes were significantly associated with CMV-positive eyes. Conclusion PCR analysis of the anterior chamber fluid is important for the confirmation of the diagnosis of viral anterior uveitis. Cytomegalovirus anterior uveitis is not uncommon in patients in southern Taiwan, and it may follow an uneventful cataract extraction in immunocompetent patients.


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