Immune-Related Conditions and Acute Leukemia in Children with Down Syndrome: A Children's Oncology Group Report

Linabery, Amy M.; Li, Wenchao; Roesler, Michelle A.; Spector, Logan G.; Gamis, Alan S.; Olshan, Andrew F.; Heerema, Nyla A.; Ross, Julie A.

doi:10.1158/1055-9965.epi-14-1181

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…The present study found an inverse association between ALL and some reported symptoms of allergic history such as allergic rhinitis/sinusitis and food allergy, which is in line with previous findings from other interview‐based studies showing that ALL cases were generally less prone to allergic symptoms than controls, 10–13,15,35–40 and in a UK study using medical‐record data 14 . However, other studies based on medical records or administrative data did not find this inverse association 16,17 .…”

Section: Discussionsupporting

confidence: 92%

“…When considering a latency period in the ESTELLE study, our results showed an association of the same order of magnitude, whereas in their meta‐analysis including four studies with a latency period between the onset of atopy and leukemia, Linabery et al. had reported a nearly completely attenuated association between atopy/allergy and childhood ALL 36 …”

Section: Discussionsupporting

confidence: 51%

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Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study

Ajrouche

Chandab

Petit

et al. 2021

Pediatric Blood & Cancer

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Context A negative association between a history of allergy and childhood acute lymphoblastic leukemia (ALL) has been reported in previous studies, but remains debated. This work aimed to investigate this association accounting for genetic polymorphisms of the Th2 pathway cytokines (IL4, IL10, IL13, and IL4R). Methods Analyses were based on the French case‐control study ESTELLE (2010‐2011). The complete sample included 629 ALL cases and 1421 population‐based controls frequency‐matched on age and gender. The child's medical history was collected through standardized maternal interview. Biological samples were collected, and genotyping data were available for 411 cases and 704 controls of European origin. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. Results In the complete sample, a significant inverse association was observed between ALL and reported history of allergic rhinitis or sinusitis (OR = 0.65 [0.42‐0.98]; P = 0.04), but there was no obvious association with allergies overall. There was an interaction between genetic polymorphisms in IL4 and IL4R (Pinteraction = 0.003), as well as a gene‐environment interaction between IL4R‐rs1801275 and a reported history of asthma (IOR = 0.23; Pint = 0.008) and eczema (IOR = 0.47; Pint = 0.06). We observed no interaction with the candidate polymorphisms in IL4 and IL13. Conclusion These results suggest that the association between allergic symptoms and childhood ALL could be modified by IL4R‐rs1801275, and that this variant could also interact with a functional variant in IL4 gene. Although they warrant confirmation, these results could help understand the pathological mechanisms under the reported inverse association between allergy and childhood ALL.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 51%

Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study

Ajrouche

Chandab

Petit

et al. 2021

Pediatric Blood & Cancer

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“…In DS children, epidemiological [1, 14–18] and pathophysiological [6, 19–22] evidences argue for a higher risk of infectious events, hematological malignancies and autoimmunity. Our work correlates for the first time detailed immunological findings and infectious events in adult patients with DS.…”

Section: Discussionmentioning

confidence: 99%

Infection risk among adults with down syndrome: a two group series of 101 patients in a tertiary center

Guffroy

Dieudonné

Uring‐Lambert

et al. 2019

Orphanet J Rare Dis

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BackgroundDown syndrome (DS) is the most common form of viable chromosomal abnormality. DS is associated with recurrent infections, auto-immunity and malignancies in children. Little is known about immunity and infections in DS at adulthood.MethodsWe studied two separate group of adults (> 18 years old) with DS in a single referral tertiary center (Strasbourg University Hospital). The first group included 37 ambulatory DS patients between November 2014 and May 2017. We analyzed exhaustive serological and immunobiological parameters, at one point, together with the prevalence of infections, autoimmune manifestations and malignancies. The second group included 64 hospitalized patients (138 stays) in the same center, between January 2005 and December 2016.ResultsOne hundred and one adult patients with DS were included. Unlike children and despite a global lymphopenia, adults with DS underwent few infections in our ambulatory group. They did not experience any malignancy and, apart from hypothyroidism, they presented only occasional autoimmune manifestations. Hospitalized DS patients were older than ambulatory ones (median age 47 years (18–73) vs. 27 (18–52), p < 0.0001) and admitted mostly for infections (76.8%). Infections were associated with epilepsy and dementia (OR 6.5 (2.2–19), p = 0.001; p = 0.0006 in multivariate analysis) and higher mortality (OR 7.4 (1.4–37), p = 0.01).ConclusionDespite persistent immunobiological abnormalities at adulthood, young ambulatory adults with DS remain healthy with a low rate of infections. Infections are associated with neurological degeneration and increase the mortality arguing for a dedicated support of older DS patients.Trial registrationClinicalTrials.gov: NCT01663675 (August 13, 2012). Hospital Clinical Research Program (PHRC): number 2012-A00466–37 (Dr Y. Alembik).Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0989-x) contains supplementary material, which is available to authorized users.

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“…The pathophysiology of asthma in children with DS is different and appears not to be caused or related to atopic tendencies; allergic rhinitis is also less common in children with DS. Reasons for this may include T-cell dysfunction or dysregulation, interference with the production of key cytokines on chromosome 21, and reduced expression of certain leukotrienes that may alter leukotriene function and response to montelukast 7–10. The particular pharmacology of montelukast in children with DS remains an area of ongoing study.…”

Section: Commentarymentioning

confidence: 99%

Is montelukast helpful in managing obstructive sleep apnoea in children with Down syndrome?

Pereira,

Gill

2024

Arch Dis Child

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Immune-Related Conditions and Acute Leukemia in Children with Down Syndrome: A Children's Oncology Group Report

Cited by 6 publications

References 30 publications

Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study

Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study

Infection risk among adults with down syndrome: a two group series of 101 patients in a tertiary center

Is montelukast helpful in managing obstructive sleep apnoea in children with Down syndrome?

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