Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation

Seo, Kang Suk; Kim, D H; Sohn, Sang Kyun; Lee, N Y; Chang, Hyun‐Ha; Kim, S W; Jeon, Soeun; Baek, Jin Ho; Kim, J G; Suh, Jang Soo; Lee, K B

doi:10.1038/sj.bmt.1705181

Cited by 96 publications

(70 citation statements)

References 28 publications

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“…Immunocompetent IL-10-deficient animals were similarly resistant to infection when given intravenous conidia (43). Consistent with this, the presence of a human IL-10 promoter polymorphism resulting in reduced IL-10 expression levels in recipients of allogeneic bone marrow transplantation was associated with a reduced incidence of invasive aspergillosis (147,153). IL-6 deficiency in both immunocompetent mice and animals treated with corticosteroids resulted in greater lung fungal contents and reduced survival associated with the impaired conidiocidal activity of lung phagocytes, which was restored after the addition of recombinant IL-6 (35).…”

Section: Cytokines In Innate Leukocyte Activationsupporting

confidence: 55%

Innate Immunity toAspergillusSpecies

Park¹,

2009

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SUMMARY All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.

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Section: Cytokines In Innate Leukocyte Activationsupporting

confidence: 55%

Innate Immunity toAspergillusSpecies

Park¹,

2009

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“…22 Furthermore, it was shown that patients with ATA haplotypes required more prolonged immunosuppression due to increased incidence of cGVHD and were more susceptible to pulmonary aspergillosis, whereas the ACC haplotype reduced the risk of pulmonary aspergillosis ninefold. 23,24 Various factors alone or in combination may account for the differences in findings among previous studies, including sample size, study power, population heterogeneity (i.e. age, ethnicity, diagnosis and disease stage) and transplant characteristics.…”

Section: Discussionmentioning

confidence: 99%

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

et al. 2011

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Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-a) and interferon gamma (IFN-c) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)50.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P50.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR50.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P50.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P50.02, HR50.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.

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“…4 In contrast, alleles with a protective role in the pathogenesis of IA were discovered in the promoter region of IL10. 5 …”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 epression in monocyte-derived dendritic cells

Mezger

Steffens

Beyer

et al. 2008

Blood

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Patients after allogeneic stem-cell transplantation (alloSCT) have an increased risk for invasive aspergillosis (IA). Here, recipients of an allograft with IA (n ‫؍‬ 81) or without IA (n ‫؍‬ 58) were screened for 84 single nucleotide polymorphisms in 18 immune relevant genes. We found 3 markers in chemokine (C-X-C motif) ligand 10 (CXCL10, 4q21, 11 101 C > T, P ‫؍‬ .007; 1642 C < G, P ‫؍‬ .003; ؊1101A < G, P ‫؍‬ .001) significantly associated with an increased risk of developing IA. Furthermore, immature dendritic cells (iDCs) exposed to Aspergillus fumigatus germlings showed markedly higher CXCL10 expression, if carrying the wild type genotype, compared with the "CGAG" high risk haplotype. In addition, serum from patients with proven/probable IA showed increased serum levels of CXCL10, compared with immunocompromised patients without IA. Thus, polymorphisms in CXCL10 determine chemokine secretion by iDCs upon exposure to A fumigatus and most likely thereby genetically determine the risk of IA after alloSCT. IntroductionInfections with Aspergillus fumigatus are frequent and life threatening in patients after allogeneic stem-cell transplantation (alloSCT). 1 Several single nucleotide polymorphisms (SNPs) were described influencing the course and outcome of invasive aspergillosis (IA). Kesh and colleagues revealed an association of IA with polymorphisms in Toll-like receptor genes TLR1 and TLR6, whereas no association could be found for the TLR4 gene. 2 In addition, it has been shown that polymorphisms in mannan-binding lectin (MBL) contribute to the occurrence of allergic bronchopulmonary aspergillosis (ABPA) by influencing the MBL plasma level and protein activity. 3 Besides MBL, further SNPs in C-type lectins were investigated leading to the identification of an association between ABPA and variants of the surfactant protein A2 gene . 4 In contrast, alleles with a protective role in the pathogenesis of IA were discovered in the promoter region of IL10. 5 MethodsThis study was approved by the local ethics committees involved in the study (University of Innsbruck, Innsbruck, Austria; University of Graz, Graz, Austria; Karolinska University Hospital, Stockholm, Sweden; and Medical Hospital II, Tübingen, Germany). Patient and sampling dataAfter approval of the local ethics committees, each consecutive patient who underwent alloSCT and who showed complete donor chimerism at the time of blood collection (as determined by short tandem repeat markers 6 ) was asked for study participation. After informed consent was obtained in accordance with the Declaration of Helsinki, blood samples from 139 consecutive patients were collected between day ϩ20 and day ϩ50 after alloSCT. Patients suffered from acute myeloid leukemia (n ϭ 57), chronic myeloid leukemia (n ϭ 26), acute lymphatic leukemia (n ϭ 20), multiple myeloma (n ϭ 11), and other hematologic disorders (n ϭ 25). Sampling was performed at the University of Innsbruck, Innsbruck, Austria (n ϭ 16), University of Graz, Graz, Austria (n ϭ 26), Karolinska University Hospital...

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Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation

Cited by 96 publications

References 28 publications

Innate Immunity toAspergillusSpecies

Innate Immunity toAspergillusSpecies

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 epression in monocyte-derived dendritic cells

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