scholarly journals Chronic Refractory Immune Thrombocytopenia Is Associated With Variants in Immune Genes

2021 ◽  
Vol 27 ◽  
pp. 107602962110598
Author(s):  
Shasha Zhao ◽  
Jingyao Ma ◽  
Xiaojing Zhu ◽  
Jialu Zhang ◽  
Runhui Wu

The pathogenesis of chronic refractory immune thrombocytopenia (C/RITP) is mechanistically complex and considerably varies across patients. Few studies have focused on the genetic characteristics of C/RITP in children. The aim of this study was to analyze and summarize the clinical manifestations and genetic characteristics of C/RITP children with mutations in immune-related genes. In the study, 51 children with variants in immune-related genes (mutation group) and 103 children with no abnormal mutations (control group) were enrolled. Children in the mutation group showed severity of hemorrhage, a higher incidence of abnormal immunological indices, and an increased expression of SLE biomarkers. The number of peripheral T and B lymphocytes in the mutation group significantly increased. Nine patients (17.6%) had probable pathogenic variant genes associated with primary immunodeficiencies ( TNFRSF13B, CARD11, CBL, and RAG2), and 42 patients (82.4%) had variants of uncertain significance in 23 genes. C/RITP patients with variants in immune-related genes had more severe bleeding, abnormal immunological indices, and an increased expression of SLE biomarker. Next-generation sequenciong (NGS) might be a useful way to differentiate those patients from C/RITP.

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4782-4782 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Bamedi Taregh ◽  
...  

Background FXIII deficiency is one of the rare bleeding disorder (RBD) that has a highest incidence in Sistan and Baluchistan province around the world. This disorder represents with different clinical manifestations ranging from mild to severe bleeding tendency including CNS bleeding. The aim of this study is to evaluate the role of PAI-14G/5Gpolymorphism in central nervous bleeding (intra and extracranial hemorrhage) system in factor XIII deficiency. Methods In this case control study was studied 32 FXIII deficient patients with CNS bleeding and also 32 patients with factor XIII deficiency without history of CNS bleeding as control group. Initially both groups were evaluated for the previously reported polymorphism of factor XIII (Trp187Argpolymorphism) in order to confirm their disorder. Then all patients were assessed for PAI-14G/5G polymorphism. Eventually obtained data was analyzed by SPSS software. Results The result of this study revealed that all study patients were homozygote for Trp187Arg polymorphism. We also found that the equal numbers of patients (4 individuals) in case and control groups were heterozygote for PAI-14G/5G polymorphism and none of patients were homozygote for this polymorphism. All heterozygote patients had intracranial hemorrhage and patients with extracranial hemorrhage had no mutation of PAI-14G/5G. Intraparenchymal was the most common site of hemorrhage and was observed in 26 patients (92.8%).We also observed subdural and epidural hemorrhage in two patients (7.1%).Anatomic regions in patients with intraparenchymal hemorrhage, were temporal in nine (32.2%), occipital in eight (28.6%), diffused intraparenchymal hemorrhage in seven (25%), tempro-occipital in two (7.1%) and subdural with temporal in two (7.1%) patients. Conclusion: It seems that PAI-14G/5G polymorphism did not any effect on occurrence of intra and extracranial hemorrhage in patients with factor XIII deficiency. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Iskander I. Zaidullin ◽  
Denis O. Karimov ◽  
Lilija K. Karimova ◽  
Milyausha F. Kabirova ◽  
Rasima R. Galimova ◽  
...  

The susceptibility to the development and progression of inflammatory periodontal diseases, which depends on genetic and external factors (smoking, stress, oral hygiene), varies widely. In the development of these diseases, an important role is played not only by the presence of periodontal pathogenic microorganisms, but also by the presence of congenital or acquired immunodeficiency, immunoregulatory defects. The immune system plays a key role in the physiological and pathological processes of periodontal tissues. In this regard, IL17, produced by CD4+ Th cells, which has both Pro-inflammatory and protective activity, is of particular interest in the pathogenesis of periodontitis. The aim of study was to identify the relationship between polymorphic loci of the IL-17A (rs2275913) and MMP-1 (rs1799750) genes and clinical manifestations of chronic periodontitis in petrochemical workers. Dental examination was performed in 92 ethylene oxide production workers with chronic periodontitis and 74 patients with chronic periodontitis who did not come into contact with chemical factors (control group). Genotyping of polymorphisms rs2275913 of the IL17A gene and rs1799750 of the MMP1 gene was performed by allele-specific real-time polymerase chain reaction (PCR). Hygienic assessment of the degree of air pollution of the working area with harmful substances was carried out by gas chromatography according to the guidelines for the determination of harmful substances in the air № 5098-89, № 3119-84. When comparing the results of studies of both groups, there were no statistically significant differences in the frequency distributions of allelic variants and genotypes of the IL-17A and MMP-1 genes. The AA/AG genotypes of the IL-17A gene were associated with an increased risk of severe disease compared to the GG genotype in workers in the main group (OR=6.1; 95% CI 1.33-28.5; p=0.021) and in the control group (OR=7.26; 95% CI 1.34-39.25; p=0.016). Carriers of the A allele in the control group increased the risk of severe chronic periodontitis by 2.4 times compared to carriers of the G allele (OR=2.41; 95% CI 1.19-4.87; p=0.014). During the dental examination of employees of the ethylene oxide plant, the clinical course of periodontal diseases was more severe in comparison with the control group, and the number of patients with severe periodontitis was twice as high. It was found that the AA/AG genotypes of the IL-17A gene and the carrier of the A allele are associated with increased susceptibility to the development of severe chronic periodontitis. The association between the MMP-1 gene polymorphism and the risk of severe forms of chronic periodontitis has not been established. A risk factor for the development of inflammatory periodontal diseases in employees of the petrochemical complex is a complex of harmful production factors.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.


Nephron ◽  
2021 ◽  
pp. 1-13
Author(s):  
Minfang Zhang ◽  
Wenyan Zhou ◽  
Shaojun Liu ◽  
Liyin Zhang ◽  
Zhaohui Ni ◽  
...  

Introduction: IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of IRGN, which needs to be distinguished from IgA nephropathy (IgAN), due to overlapping clinical and pathological features. The key factor in the pathogenesis of IgAN is galactose-deficient IgA1 (Gd-IgA1). However, the mechanism of glomerular IgA deposition in patients with IgA-IRGN is unclear. Therefore, we evaluated whether Gd-IgA1 could be a useful biomarker to distinguish between these 2 diseases. Methods: A case-control study was conducted to analyze the clinical and pathological characteristics of 12 patients with IgA-IRGN. The intensity and distribution of glomerular Gd-IgA1 (KM55) staining in renal biopsies were assessed. The control group consisted of 15 patients diagnosed with IgAN and an additional 17 patients with glomerulopathy involving IgA deposition. Results: The main clinical manifestations of patients with IgA-IRGN were nephrotic-range proteinuria, hematuria, acute renal injury, and hypocomplementemia. Active lesions were the leading pathological feature, while focal segmental sclerosis was rare. Half of the patients exhibited hump-shaped subepithelial deposits. Glomerular KM55 staining was negative in 7 patients, trace in 4 patients, and 2+ in 1 patient. The median intensity of KM55 staining in IgA-IRGN patients was 0 (range 0∼2+), which was significantly lower than that of primary IgAN patients (median 2+, range 1+∼3+). The receiver operating characteristic analysis demonstrated that the optimal cutoff level to identify these 2 diseases was 0.5+. Conclusions: Glomerular KM55 staining intensity might be helpful to distinguish IgA-IRGN from primary IgAN. Weak or negative staining may favor IgA-IRGN. In addition, integrated analysis including clinical data, pathological findings, and prognostic information would further improve the differential diagnosis.


2021 ◽  
pp. jim-2021-001788
Author(s):  
Xiumei Liu ◽  
Xueming Wang ◽  
Xiaoling Zhang ◽  
Ai hua Cao

Tic disorders (TD) are childhood-onset neurological disorders. Immune system dysregulation has been postulated to play a role in TD, and its mechanisms likely involve dysfunctional neural-immune cross-talk, which ultimately leads to altered maturation of the brain pathways that control different TD clinical manifestations and behavioral and emotional damages. Clinical studies have demonstrated an association between TD and allergies and overactive immune responses at a systemic level. In this study, the Yale Global Tic Severity Scale was taken as a global measure of tic severity. Compared with the control group, the group of children with TD plus allergic diseases displayed significantly increased Yale total scores (p<0.05), which suggests that children with TD plus allergic diseases have heavier tic symptoms. Both motor and vocal tic scores are higher in the group of children with TD plus allergy compared with the control group. We counted immune cell subpopulations using FACS. T lymphocyte subset comparison of CD3, CD4, CD8, and CD4:CD8 expression ratios revealed that the level of CD3, CD4, and CD4:CD8 in children with TD plus allergic diseases was significantly lower than those of children with TD without allergic diseases. These differences were statistically significant (p<0.05) and suggest that children with TD plus allergic diseases have imbalanced T lymphocyte subsets. We concluded that allergy increased the severity of TD through an imbalance in cellular immunity. Studies need to be done to show whether treatment of allergic symptoms leads to a decrease in TD manifestations.


2016 ◽  
Vol 56 (3) ◽  
pp. 129
Author(s):  
Nadya Arafuri ◽  
Pudjo Hagung Widjajanto ◽  
Ekawaty L. Haksari

Background Albumin transfusion for the treatment of neonatal hypoalbuminemia may reduce morbidity. In conditions with disrupted endothelial integrity (e.g., sepsis and critical illness), the administered albumin may leak into the interstitial space, hence, serum albumin levels may fall below expected levels after transfusion. To date, few studies have been done to evaluate the risk factors for failure to achieve normal neonatal albumin levels after transfusion.Objectives To determine the risk factors for failure to achieve normal neonatal albumin levels after transfusion.Methods We performed a case-control study in the Neonatal Ward of Dr. Sardjito Hospital from 2007 to 2012. Normal albumin level was defined as above 3 g/dL. The case group included neonates with post-transfusion albumin levels <3 g/dL and the control group included those with post-transfusion albumin ≥3 g/dL. Subjects received intravenous transfusions of 25% or 20% albumin according to the clinical standard of the Neonatal Ward of Dr. Sardjito Hospital. Neonates with very low birth weight, severe birth trauma, burn injuries, severe bleeding, or incomplete medical records were excluded. The data were analyzed with logistic regression test.Results From January 2007 to December 2012, 124 neonates were enrolled in the study. Multivariate analysis showed that low albumin levels before transfusion (OR 12.27; 95%CI 2.17 to 69.30), presence of critical illness (OR 4.01; 95%CI 1.49 to 10.79), diagnosis of sepsis (OR 3.56; 95%CI 1.36 to 9.32), and the >24-hour interval between albumin examination and transfusion (OR 0.06; 95%CI 0.01 to 0.37) were significant risk factors affecting the failure to achieve normal albumin levels.Conclusions Failure to achieve normal albumin levels after transfusion in neonates was significantly associated with low albumin level prior to transfusion, critical illness, sepsis, and >24-hour interval between transfusion and post-transfusion albumin examination.[Paediatr Indones. 2016;56:129-33.].


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jiaming Li ◽  
Zhaoyue Wang ◽  
Lan Dai ◽  
Lijuan Cao ◽  
Jian Su ◽  
...  

We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP). Eighty-eight patients were separated into the control (cyclosporine A plus prednisone) and experimental (rapamycin plus prednisone) groups. The CD4+CD25+CD127lowregulatory T (Treg) cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR) was similar in both groups (experimental group versus control group: 58% versus 62%,P=0.70). However, sustained response (SR) was more pronounced in the experimental group than in the control group (68% versus 39%,P<0.05). Both groups showed similar incidence of adverse events (7% versus 11%,P=0.51). As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P<0.001); however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.


2011 ◽  
Vol 4 (6) ◽  
pp. 338-343 ◽  
Author(s):  
Elias Armenis ◽  
Nikolaos Pefanis ◽  
Georgios Tsiganos ◽  
Panagiotis Karagounis ◽  
Panagiotis Baltopoulos

Sports activities cause increased loads in elite athletes’ joints. Current scientific knowledge highlights the importance of applied mechanical loads on the physiology and pathophysiology of the articular cartilage. Thus, it is possible that sporting activity has a role in the development of osteoarthritis (OA), a painful and damaging joint disease. The aim of the present study was to investigate and record osteoarthritic alterations in the ankle and foot complex in former Greek soccer players and also compare them with those in the general population. The study sample consisted of 170 male, former elite soccer players, aged between 42 and 55 years (mean = 49.8 years, standard deviation [SD] = 7.4). A control group of 132 men, aged between 42 and 55 years (mean, 50.7 years, SD = 9.9), with no regular athletic activity were examined. The development of osteoarthritic alterations was recorded through a questionnaire and clinical and radiological examination. Radiographic analysis of the images in former athletes group showed not only more signs of cartilage degeneration in comparison with the control group (P < .05) but also similar clinical manifestations (pain and impaired mobility; P > .05). Osteophyte formation is a frequent disease among former soccer players—with variations on radiographic images—but it does not appear in their clinical picture. However, it is likely that both spurs and subchondral sclerosis (main findings) are preclinical manifestations of OA. Levels of Evidence: Prognostic, Level II


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 47.2-47
Author(s):  
C. Gioia ◽  
B. Lucchino ◽  
C. Iannuccelli ◽  
G. Dolcini ◽  
M. DI Franco

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D’Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declared


2020 ◽  
pp. 8-14
Author(s):  
R. M. Mallaeva ◽  
A. N. Makhinko ◽  
M. B. Uzdenov

The purpose of the study is to improve rehabilitation treatment of patients with chronic pancreatitis (CP) at inpatient stage by strengthening pharmacological potential of drug therapy due to inclusion of therapeutic physical factors (TPF) in therapeutic programs. Materials and methods. 159 patients with acute CP were observed. By simple randomization, 4 groups were formed: the control group (MG, 39 people) received standard drug therapy; 1st comparison group (GC1; 38 people) additionally received TPF; GC2 (40 people) in addition to treatment in GC1 had drinking mineral water «Slavyanovskaya»; in main group (42 people) in addition to the treatment in GC2 got preformed peloidotherapy on the cervical-collar zone. All the patients underwent the evaluation of clinical score and quality of life before and after medical rehabilitation. Results. In MG, clinical symptomatology leveling was by 78,2% (p<0,01), in GC1 — by 71,5% (p<0,01), GC2 — by 62,3% (p<0,01), CG — by 57,2% (p<0,01) on average immediately after the treatment, which was in a clear correlation with indicators of quality of life. In the long term (in 6 and 12 months), the advantage of combination therapy was noted with the same validity, the preservation of the achieved positive result was mostly noted in the MG: after 6 months the improvement in physical health compared to the initial values was noted by 34,4% (p<0,01), after 12 months — by 24,0% (p<0,05); mental — by 32,3% (p<0,01) and 22,5% (p<0,05), respectively. In both comparison groups, positive dynamics was 10–12% lower, and in the control group, after 6 months, there was only a tendency to improve quality of life indicators. Conclusion. The inclusion of TPF in the programs of the inpatient stage of medical rehabilitation of patients with chronic pancreatitis by strengthening the pharmacological potential of drug therapy contributes to the leveling of clinical manifestations (abdominal pain, dyspepsia and diarrhea), the result of which is an improvement in the quality of life of this category of patients.


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