Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells

Suhoski, Megan M.; Perez, Elena E.; Heltzer, Meredith; Laney, Ayanna O.; Shaffer, Lisa G.; Saitta, Sulagna C.; Nachman, Sharon; Spinner, Nancy B.; June, Carl H.

doi:10.1016/j.clim.2008.03.522

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…Suhoski et al reported that the genes undergoing deletion by 1p36 microdeletion encode the costimulatory molecules of the TNF receptor superfamily (TNFRSF) [15]. However, primary immunodeficiency due to 1p36 deletion has not yet been reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

Do microdeletions lead to immune deficiency?

Karaman

Hazan²,

Erdem

et al. 2020

cejoi

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Introduction: microdeletion syndromes may be accompanied by immunological disorders. this study aimed to evaluate the clinical and laboratory data as well as the immune functions of patients diagnosed with a microdeletion syndrome.Material and methods: 39 patients diagnosed with microdeletion syndrome who were monitored at the Pediatric genetics and immunology clinics at dr. Behcet Uz children's hospital were included in this study. all data for this research were obtained from patient records and by individual consultation with their parents.Results: Of the 39 patients, 15 were monitored for a diagnosis of Williams syndrome, 12 for digeorge syndrome, 4 for Prader-Willi syndrome, 2 for Wolf-hirschhorn syndrome, 1 for a 1p36 deletion, 1 for Smith-magenis syndrome, 2 for Trichorhinophalangeal syndrome type 2 (TrPS2), and 2 for cri-du-chat syndrome. Of these 39 patients, 10 (25.6%) had a medical history of frequent upper respiratory tract infections. One of the cases with TrPS2 and another with Smith-magenis syndrome had previously received intravenous antibiotic therapy for infectious disease. Five of the 12 patients with digeorge syndrome had low T lymphocytes. Two of the patients with digeorge syndrome with a history of frequent infections, with hypogammaglobinemia, and low lymphocytes were receiving regular intravenous immunoglobulin (iVig) replacement.Conclusions: it must be taken into account that patients with microdeletion syndromes, especially those with digeorge syndrome, may also have immunodeficiencies; therefore, these patients should be closely monitored to prevent development of any complications.

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Section: Discussionmentioning

confidence: 99%

Do microdeletions lead to immune deficiency?

Karaman

Hazan²,

Erdem

et al. 2020

cejoi

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“…16,17 Membrane type ligand OX40L interacts with membranetype OX40 to mediate activation, quantity expansion, transportation, and life expansion of CD4+ T cells, as well as, to promote the formation of germinal centers and the maturation of DCs. [18][19][20][21] The interactions of OX40/OX40L have been found to play a critical role in the development of many infl ammatory and autoimmune diseases. 22,23 Some studies 24,25 found that many asthmatic responses were not induced in OX40L-defi cient BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

SOX40L: An Important Inflammatory Mediator in Adult Bronchial Asthma

Zhu

et al. 2012

Ann Acad Med Singap

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Introduction: The role of soluble OX40 ligand (sOX40L) in adult bronchial asthma is unclear. This study aims to determine the serum concentrations of sOX40L in adult patients with bronchial asthma, and discussed its relationship with pulmonary function. Materials and Methods: We measured the pulmonary function using the spirometer and detected the serum concentrations of sOX40L by enzyme linked immunosorbent assay (ELISA) in 19 healthy persons in the control group, 58 acute asthmatic adult patients who were grouped according to their disease severity: 18 mild grade, 24 moderate grade, 16 severe grade, and 24 persons in a stable asthmatic group. Results: The serum concentrations of sOX40L in asthmatic adult patients (6.80 ± 4.95 ng/L) were distinctly higher than those in the control group (3.98 ± 2.83 ng/L, P <0.05), and they were negatively correlated with pulmonary function indexes (FEV1%, FVC%, FEV1/FVC) (r = –0.754, P <0.01, r = –0.557, P <0.01, r = –0.457, P <0.01, respectively). Moreover, the serum concentrations of sOX40L showed obvious differences among control, mild, moderate, and severe groups (3.98 ± 2.83, 4.87 ± 1.89, 6.97 ± 5.91, 8.71 ± 5.18 ng/L, respectively; P <0.01). The concentrations of sOX40L decreased to the same extent as the control group after therapeutic treatments were provided to the asthmatic adult patients. Conclusion: The concentrations of sOX40L were found to be high in adult asthmatic patients and were associated with the severity of the disease. Therefore, sOX40L could be a potential inflammatory mediator in the pathogenesis of asthma. Key words: Co-stimulatory, Pulmonary function, ELISA, Soluble OX40 ligand

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Immunologic and Genetic Contributors to CD46-Dependent Immune Dysregulation

et al. 2023

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Mutations in CD46 predispose to atypical hemolytic uremic syndrome (aHUS) with low penetrance. Factors driving immune-dysregulatory disease in individual mutation carriers have remained ill-understood. In addition to its role as a negative regulator of the complement system, CD46 modifies T cell-intrinsic metabolic adaptation and cytokine production. Comparative immunologic analysis of diseased vs. healthy CD46 mutation carriers has not been performed in detail yet. In this study, we comprehensively analyzed clinical, molecular, immune-phenotypic, cytokine secretion, immune-metabolic, and genetic profiles in healthy vs. diseased individuals carrying a rare, heterozygous CD46 mutation identified within a large single family. Five out of six studied individuals carried a CD46 gene splice-site mutation causing an in-frame deletion of 21 base pairs. One child suffered from aHUS and his paternal uncle manifested with adult-onset systemic lupus erythematosus (SLE). Three mutation carriers had no clinical evidence of CD46-related disease to date. CD4+ T cell-intrinsic CD46 expression was uniformly 50%-reduced but was comparable in diseased vs. healthy mutation carriers. Reconstitution experiments defined the 21-base pair-deleted CD46 variant as intracellularly—but not surface-expressed and haploinsufficient. Both healthy and diseased mutation carriers displayed reduced CD46-dependent T cell mitochondrial adaptation. Diseased mutation carriers had lower peripheral regulatory T cell (Treg) frequencies and carried potentially epistatic, private rare variants in other inborn errors of immunity (IEI)-associated proinflammatory genes, not found in healthy mutation carriers. In conclusion, low Treg and rare non-CD46 immune-gene variants may contribute to clinically manifest CD46 haploinsufficiency-associated immune-dysregulation.

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Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells

Cited by 3 publications

References 33 publications

Do microdeletions lead to immune deficiency?

Do microdeletions lead to immune deficiency?

SOX40L: An Important Inflammatory Mediator in Adult Bronchial Asthma

Immunologic and Genetic Contributors to CD46-Dependent Immune Dysregulation

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