FC gamma receptor polymorphisms in patients with immune thrombocytopenia

Pavkovic, Marica; Petlichkovski, Aleksandar; Каранфилски, Оливер; Čevreska, Lidija; Stojanović, Aleksandar

doi:10.1080/10245332.2017.1377902

Cited by 15 publications

(15 citation statements)

References 42 publications

(53 reference statements)

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“…In a recent study, Pavkovic et al examined the association of FCG gene mutation (FCGR2A) with chronic ITP expression in 120 adult ITP patients, where a significant association between polymorphism in this gene and chronic ITP was observed. However, these researchers recommended conducting a study with a larger sample size [15]. On the other hand, our study there did not demonstrate a relationship of the type of FCG genotype and the history of infection with chronic disease.…”

Section: Discussioncontrasting

confidence: 67%

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

Bahoush

Ghasemi

Razavi

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which autoantibodies react with platelet surface antigens and results in mild to severe thrombocytopenia due to decreased platelet count or inhibition of platelet production. Given the relatively high prevalence of ITP among children and the lack of standard diagnostic testing for the diagnosis of chronic disease, this study evaluated the predictive value of risk factors for chronic ITP in hospitalized patients. METHODS: This prospective cohort study was performed on 65 children with ITP who referred to Ali Asghar and Rasool Akram Hospitals in Tehran, Iran, during the years 2017 and 2018. Relationships between different risk factors, including age of diagnosis, gender, white cell count, primary platelet count, mean platelet volume (MPV), history and type of the previous patient infection, FCG gene mutation, and type of FCG mutation with a chronic disease incidence were investigated using multiple logistic regression model. RESULTS: Of 65 patients, 31 (47.69%) were male and 34 (52.31%) were female included in the study. Twenty-eight patients (43.08%) had acute ITP and 37 (56.92%) had chronic ITP. Frequency of FCG gene mutation in patients with chronic and acute type ITP was 16.36% and 7.27%, respectively (p = 0.51). No association was found between the history of the previous infection and its type with the chronic incidence of ITP. The multiple logistic regression model showed that three factors, including the absolute number of lymphocytes, age of diagnosis, and primary white blood cells (WBC) count were directly linked to chronic ITP. Furthermore, three factors of platelet, sex, and MPV were indirectly related to chronic ITP. In addition, the absolute number of lymphocytes, age of diagnosis and primary WBC count were significantly associated with chronic ITP. The receiver operating characteristic analysis showed that the cutoff rate of these factors was 0.31. Further analysis of these risk factors in comparison with the gold standard demonstrated that the diagnostic sensitivity and specificity of these risk factors for chronic ITP were 73.08% and their specificity was 88.57%, indicating the high importance and predictive power of these risk factors. CONCLUSIONS: According to the results of this study, for the first time in Iran, six risk factors, including the absolute number of lymphocytes, age at diagnosis, sex, MPV level, platelet level at time of diagnosis, and primary WBC count were considered as the most important risk factors affecting the incidence of chronic ITP. Of course, more comprehensive studies can definitely lead to more comprehensive models.

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Section: Discussioncontrasting

confidence: 67%

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

Bahoush

Ghasemi

Razavi

et al. 2020

Open Access Maced J Med Sci

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“…This association was confirmed in a GWAS (45). Finally, concerning immune thrombocytopenia, a meta-analysis ascertained an association between FCGR2A -p.166His and susceptibility to childhood ITP, but not adult ITP (46, 75, 141, 142). Taking the genetic associations into account, it may be speculated that a reduced function of FcγRIIA with the p.166Arg variant is associated with a failure to clear circulating immune complexes, which is a hallmark of SLE.…”

Section: Genetic Variation In Fcgr2/3 Genes: Associations With Diseasementioning

confidence: 99%

“…Considering ulcerative colitis, there is a small increased susceptibility to develop the disease with the p.176Val allele (77). Finally, several studies have associated the FCGR3A -p.176Val/Val genotype with increased susceptibility for ITP (19, 75, 141, 142).…”

Section: Genetic Variation In Fcgr2/3 Genes: Associations With Diseasementioning

confidence: 99%

Genetic Variation in Low-To-Medium-Affinity Fcγ Receptors: Functional Consequences, Disease Associations, and Opportunities for Personalized Medicine

et al. 2019

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Fc-gamma receptors (FcγR) are the cellular receptors for Immunoglobulin G (IgG). Upon binding of complexed IgG, FcγRs can trigger various cellular immune effector functions, thereby linking the adaptive and innate immune systems. In humans, six classic FcγRs are known: one high-affinity receptor (FcγRI) and five low-to-medium-affinity FcγRs (FcγRIIA, -B and -C, FcγRIIIA and -B). In this review we describe the five genes encoding the low-to-medium -affinity FcγRs (FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B), including well-characterized functionally relevant single nucleotide polymorphisms (SNPs), haplotypes as well as copy number variants (CNVs), which occur in distinct copy number regions across the locus. The evolution of the locus is also discussed. Importantly, we recommend a consistent nomenclature of genetic variants in the FCGR2/3 locus. Next, we focus on the relevance of genetic variation in the FCGR2/3 locus in auto-immune and auto-inflammatory diseases, highlighting pathophysiological insights that are informed by genetic association studies. Finally, we illustrate how specific FcγR variants relate to variation in treatment responses and prognosis amongst autoimmune diseases, cancer and transplant immunology, suggesting novel opportunities for personalized medicine.

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“…There are several points worth noting about this meta‐analysis. Firstly, the investigated polymorphisms were all missense mutations, and the nucleotide substitutions caused by mutant alleles of these polymorphisms could impact the binding of Fc gamma receptors with Ig, which might subsequently lead to immune dysfunction and give rise to multiple immunological disorders including ITP . Secondly, FcγRIIa is the only class of Fc gamma receptors expressed on platelets, and engagement of this receptor on platelets by immune complexes triggers intracellular signalling events that lead to platelet activation and aggregation .…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, it is possible that functional genetic polymorphisms of Fc gamma receptors ( FCGR ) may alter the binding affinities of Fc gamma receptors and impact individual susceptibility to ITP. Recently, several studies already explored potential associations of FCGR2A H131R , FCGR2B I232T and FCGR3A F158V polymorphisms with ITP in diverse populations, with inconsistent results . Therefore, we conducted a meta‐analysis of all relevant studies to better analyse the effects of FCGR polymorphisms on individual susceptibility to ITP.…”

Section: Introductionmentioning

confidence: 99%

Associations between FCGR polymorphisms and immune thrombocytopenia: A meta‐analysis

Chen

Gao

et al. 2019

Scand J Immunol

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Several studies already explored associations between Fc gamma receptor (FCGR) polymorphisms and immune thrombocytopenia (ITP), but the results of these studies were not consistent. Consequently, we conducted a meta-analysis of relevant studies to better analyse the effects of FCGR polymorphisms on individual susceptibility to ITP. PubMed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Totally 17 studies were eligible for analyses (1200 cases and 1723 controls). Significant associations with ITP were observed for FCGR3A F158V polymorphism in dominant (P < 0.0001, OR = 0.47, 95% CI 0.39-0.57), recessive (P < 0.0001, OR = 2.03, 95% CI 1.58-2.61), overdominant (P < 0.0001, OR = 1.42, 95% CI 1.19-1.69) and allele (P < 0.0001, OR = 0.58, 95% CI 0.51-0.65) models in overall analyses. But we did not observe any significant associations with ITP for FCGR2A H131R and FCGR2B I232T polymorphisms in overall analyses. Subgroup analyses by ethnicity yielded similar positive results for FCGR3A F158V polymorphism in both Asians and Caucasians. Furthermore, subgroup analyses by type of disease revealed that FCGR2A H131R polymorphism was significantly associated with childhood-onset ITP, and FCGR3A F158V polymorphism was significantly associated with both childhood-onset and adult-onset ITP. In summary, our findings suggested that FCGR2A H131R polymorphism may serve as a potential genetic biomarker of childhood-onset ITP, while FCGR3A F158V polymorphism may serve as a potential genetic biomarker of both childhood-onset and adult-onset ITP.

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FC gamma receptor polymorphisms in patients with immune thrombocytopenia

Abstract: Our results suggest possible role of FCGR3A polymorphism in the etiology, development and clinical outcome of ITP, but larger prospective studies are needed to confirm these results.

Cited by 15 publications

References 42 publications

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

Genetic Variation in Low-To-Medium-Affinity Fcγ Receptors: Functional Consequences, Disease Associations, and Opportunities for Personalized Medicine

Associations between FCGR polymorphisms and immune thrombocytopenia: A meta‐analysis

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