Interstitial lung disease (ILD) and severe ITP

Fontana, Vincenzo; Horstman, Lawrence L.; Donna, Elio; Dudkiewicz, Pamela; Ahn, Eugene; Ahn, Yeon S.

doi:10.1080/10245330600938281

Cited by 11 publications

(10 citation statements)

References 10 publications

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“…Activation of acute phase response with connection to the complement and coagulation systems have been suggested as key processes in acute ILD events following blood transfusions (transfusion related acute lung injury; TRALI) [26] and in patients with idiopathic thrombocytopenic purpura (ITP) [27]. Acute phase responses can be induced by bronchoscopy with bronchoalveolar lavage [28].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

et al. 2011

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Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control.

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Section: Discussionmentioning

confidence: 99%

Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

et al. 2011

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“…In fact as the lung vasculature is the main portal system in the body, it is highly exposed to the activity of circulating inflammatory humoral and cellular mediators (including platelets) and thus it constitutes the ideal setting for the complete expression of some of the most characteristic pathogenic features of SSc, i.e., vascular dysfunction and subsequent aberrant vessel and tissue remodeling. Moreover, as suggested by the pathogenesis of transfusion-related acute lung injury (TRALI; Nurden, 2011), by clinical reports of non-SSc interstitial lung disease after the onset of severe idiopathic thrombocytopenic purpura (ITP; Fontana et al, 2007) and finally by detection of platelet activation markers in bronchoalveolar lavages of SSc patients with active pulmonary involvement (Kowal-Bielecka et al, 2005), lungs constitute a preferential target for platelet-induced inflammatory injury.…”

Section: Platelet Activation and Pathogenesis Of Sscmentioning

confidence: 99%

The role of platelets in the pathogenesis of systemic sclerosis

et al. 2012

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Systemic sclerosis (SSc) is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients’ quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity, and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including SSc. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

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“…However, ITP can also induce inflammation through platelet dysfunction. Recent research revealed that the acute phase of platelet destruction in severe ITP may trigger inflammation in the lung, which may induce interstitial lung disease (9). Furthermore, platelets mediate inflammation and immune-mediated disorders through multiple mechanisms, such as release of pro-inflammatory mediators, surface inflammation-related molecules, and interaction with leukocytes and endothelial cells (10, 11).…”

Section: Introductionmentioning

confidence: 99%

Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia

Shao

et al. 2017

Front. Immunol.

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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP. We recruited 312 ITP inpatients and 154 healthy participants in this case–control study. Inflammation-related SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. The expression of TNFAIP3 mRNA was determined by quantitative real-time RT-PCR. All SNPs in healthy controls were consistent with Hardy–Weinberg equilibrium. Statistical analysis revealed that rs10499194 in TNFAIP3 was significantly associated with a decreased risk of ITP after Bonferroni multiple correction (codominant, CT vs. CC, OR = 0.431, 95% CI = 0.262–0.711, p = 0.001; dominant, TT/CT vs. CC, OR = 0.249, 95% CI = 0.141–0.440, p = 0.000). Besides, TNFAIP3 expression was significantly higher in patients with CT and pooled CT/TT genotypes compared with CC genotype (p = 0.001; p = 0.001). Interestingly, rs10499194 was also associated with corticosteroid-sensitivity (codominant, CT vs. CC, OR = 0.092, 95% CI = 0.021–0.398, p = 0.001; dominant, TT/CT vs. CC, OR = 0.086, 95% CI = 0.020–0.369, p = 0.001; allelic, T vs. C, OR = 0.088, 95% CI = 0.021–0.372, p = 0.001). Furthermore, no significant association was found between inflammation-related SNPs and the severity or refractoriness of ITP after Bonferroni multiple correction. Our findings suggest that rs10499194 may be a protective factor for susceptibility and corticosteroid sensitivity in ITP patients.

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Interstitial lung disease (ILD) and severe ITP

Abstract: We report an association of ILD with severe refractory ITP. ILD was detected in acute phase of platelet destruction, suggesting that platelet destruction may have triggered inflammation in the lung, leading to ILD.

Cited by 11 publications

References 10 publications

Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

The role of platelets in the pathogenesis of systemic sclerosis

Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia

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