Refractory immune thrombocytopenia: Lessons from immune dysregulation disorders

Costagliola, Giorgio; Consolini, Rita

doi:10.3389/fmed.2022.986260

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Additional knowledge in these areas is important because specific management strategies not typically used in rITP have been employed successfully in m-IC disorders, including mTOR inhibitors in pES, IPEX, TFATC1, PRKCD and PASLI; sirolimus and mycophenylate in autoimmune lymphoproliferative syndrome; abatacept in CTLA4 and LRBA deficiencies; etanercept in ADA2, ruxolitinib in JAK1-and JAK2-related disorders, JAK inhibitors and anti-IL6 antibody in STAT3 gain of function syndromes and trametinib and selumetinib in RAS-associated leukoproliferative disorders, among others (reviewed in Refs [24,26]).…”

Section: Ge N Etic S a N D 'Sy N Drom Ic ' Itpmentioning

confidence: 99%

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Pathogenesis of refractory ITP: Overview

Cines

2023

Br J Haematol

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SummaryA subset of individuals with ‘primary’ or ‘idiopathic’ immune thrombocytopenia (ITP) who fail to respond to conventional first‐ and second‐line agents or who lose responsiveness are considered to have ‘refractory’ disease (rITP), placing them at increased risk of bleeding and complications of intensive treatment. However, the criteria used to define the refractory state vary among studies, which complicates research and clinical investigation. Moreover, it is unclear whether rITP is simply ‘more severe’ ITP, or if there are specific pathogenic pathways that are more likely to result in refractory disease, and whether the presence or development of rITP can be established or anticipated based on these differences. This paper reviews potential biological features that may be associated with rITP, including genetic and epigenetic risk factors, dysregulation of T cells and cytokine networks, antibody affinity and specificity, activation of complement, impaired platelet production and alterations in platelet viability and clearance. These findings indicate the need for longitudinal studies using novel clinically available methodologies to identify and monitor pathogenic T cells, platelet antibodies and other clues to the development of refractory disease.

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Section: Ge N Etic S a N D 'Sy N Drom Ic ' Itpmentioning

confidence: 99%

“…25 However, the relevance of these findings to the development of rITP needs further investigation (reviewed in Ref. [26]). Polymorphisms in immune receptors, cytokines, chemokines, transcription factors and micro RNAs have also been reported in patients with ITP.…”

Section: Ge N Etic S a N D 'Sy N Drom Ic ' Itpmentioning

confidence: 99%

Pathogenesis of refractory ITP: Overview

Cines

2023

Br J Haematol

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Evaluating the prevalence of inborn errors of immunity in adults with chronic immune thrombocytopenia or Evans syndrome

Jiang,

Rosenlind,

Baxter

et al. 2023

Blood Advances

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Inborn errors of immunity (IEI) are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Autoimmune cytopenias such as immune thrombocytopenia (ITP) and Evans syndrome (combination of ITP and autoimmune hemolytic anemia) are increasingly recognized phenotypes of IEI. While recent findings suggest that IEI may commonly underlie pediatric ITP and Evans syndrome, its prevalence in adult patients with these disorders remains undefined. This study sought to estimate the prevalence of underlying IEI among adults with persistent or chronic ITP or Evans syndrome using a next generation sequencing panel encompassing 370+ genes implicated in IEI. Forty-four subjects were enrolled from an outpatient adult hematology clinic at a tertiary referral center in the U.S., with a median age of 49 years (range, 20 to 83). Fourteen subjects (31.8%) had secondary ITP, including 8 (18.2%) with Evans syndrome. No cases of IEI were identified despite a high representation of subjects with personal history of autoimmunity (45.5%) and early onset of disease (median age at diagnosis of 40 years [range, 2 to 77]), including 20.5% who were initially diagnosed as children. Eight subjects (18.2%) were found to be carriers of pathogenic IEI variants, which in the heterozygous state are not disease-causing. One case of TUBB1-related congenital thrombocytopenia was identified. While systematic screening for IEI has been proposed for pediatric patients with Evans syndrome, findings from this real-world study suggest that inclusion of genetic testing for IEI in the routine work-up of adults with ITP and Evans syndrome has low diagnostic yield.

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