Interleukin-7 receptor α-chain haplotypes differentially affect soluble IL-7 receptor and IL-7 serum concentrations in children with type 1 diabetes

Seyfarth, Julia; Lundtoft, Christian; Förtsch, Katharina; Ahlert, Heinz; Rosenbauer, Joachim; Bächle, Christina; Roden, Michael; Holl, Reinhard W.; Mayatepek, Ertan; Kummer, Sebastian; Meißner, Thomas; Jacobsen, Marc

doi:10.1111/pedi.12665

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…* Borilova Linhartova P. et al, 2018 [9] CP does not influence the circulating IL-8 levels. Patients with T1DM+CP had higher circulating IL-8 levels than healthy controls+P/non-P. Seyfarth J. et al, 2018 [32] Only T1DM children with the protective haplotype had lower IL-7 serum levels. Al-Lahham Y. et al, 2017 [33] IL-18 rs187238 was not associated with T1DM in a Euro-Brazilian population.…”

Section: Discussionmentioning

confidence: 97%

“…SNPs for IL-7 in T1DM patients were investigated in several valuable works [14,20,31,32]. Hoffman M. et al [14] revealed higher sIL-7R serum concentrations at T1DM onset and decreasing levels during therapy, whereas IL-7 was only higher in long-term patients compared to controls.…”

Section: Discussionmentioning

confidence: 99%

“…According to Lundtoft C. et al [30], IL-7Rα variants may contribute to disease susceptibility against T1DM. Finally, Seyfarth J. et al [32] pointed out that only T1DM children with the protective haplotype had lower IL-7 serum levels.…”

Section: Discussionmentioning

confidence: 99%

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Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

D’Agostino,

Valentini,

Dolci

2024

Children

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Diabetes can trigger an increase in cytokine levels leading to the production of C-reactive protein and fibrinogen. These molecules promote subclinical inflammation, causing the expression of adhesive molecules and endothelial dysfunction. Despite the lack of a comprehensive panel for single-nucleotide polymorphisms (SNPs) for interleukins associated with type 1 diabetes mellitus (T1DM), understanding the inflammatory role of SNPs is crucial because periodontitis, the sixth complication of diabetes, is influenced via these genetic variations. This review focuses on the interleukin levels in T1DM patients with and without periodontitis, with a particular focus on childhood and on SNPs when reported. A search of PubMed and Scopus identified 21 relevant studies from the past five years. Several ILs were analyzed, emphasizing that T1DM still needs to be thoroughly explored regarding an IL polymorphisms panel; however, the last five years have led to the increased independence of this condition, causing autonomous inflammatory effects, which require further investigation. The periodontitis and T1DM association in children and adolescents represents a severe gap in the literature that should be filled; this scarce presence of studies serves as motivation for further clinical research.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

D’Agostino,

Valentini,

Dolci

2024

Children

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“…Serum of study participants was stored at −80°C for concomitant IL-7 measurement at the University Childrens Hospital in Duesseldorf. Serum IL-7 concentrations were measured as described previously [16,20]. In brief, we used a commercially available highly sensitive ELISA (Human IL-7 Quantikine HS ELISA kit, R&D Systems) according to manufacturer's instructions.…”

Section: Serum Il-7 Measurementmentioning

confidence: 99%

Higher Interleukin-7 serum concentrations in patients with cystic fibrosis correlate with impaired lung function

Seyfarth

Sutharsan

Ricken

et al. 2019

Journal of Cystic Fibrosis

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Background: Patients with cystic fibrosis (CF) are highly susceptible to infection and colonization of pulmonary epithelia. Repeated and chronic infections may affect disease course and efficacy of host immune protection. Higher Interleukin (IL)-7 serum levels, indicating impaired T-cell response to IL-7, have been described for chronic viral and mycobacterial infections. Methods: Time course measures of IL-7 serum concentrations in patients with CF (n = 164; n = 78 for the second time point) and healthy controls (n = 60) were done. CF patients were characterized for disease severity parameters as well as infection status and association with IL-7 serum levels was determined. Results: CF patients had significantly higher IL-7 serum concentrations as compared to healthy controls (9.79 pg/ml, IQR 6.76-13.6 versus 4.55 pg/ml, IQR 2.76-9.51, p b .001). IL-7 serum levels were negatively correlated with individual CF patient's BMI (r = −0.19, p = .021) and a tendency of increased IL-7 levels in Staphylococcus aureus infected CF patients was found. Linear regression of multiple parameters revealed significant negative correlation of FEV1 %pred with IL-7 serum concentrations in patients with CF (ß-coefficient: −0.04, 95% confidence interval [−0.08; −0.003], p = .034). Time course analyses after 1 year +/− 6 months showed increased IL-7 serum levels (time point 1:9.26 pg/ml, IQR 6.94-13.12 time point 2:10.86 pg/ml, IQR 9.14-14.76, p = .016) that correlated negatively with decreased FEV1 %pred during CF disease course. Conclusions: High IL-7 serum levels were found in CF patients and correlated with impaired lung function during CF disease course. As a candidate biomarker of T-cell dysfunction, higher IL-7 serum level may also indicate worsened immune competence of patients with CF.

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“…The rs6897932 T-allele is associated with protection against autoimmune diseases and causes diminished sIL-7R expression [5]. As a consequence, protective allele carriers generally have lower sIL-7R serum levels with potential effects on sIL-7R reservoir function and IL-7 availability [8,9]. We have previously found using cell lines that the rs6897932 Tallele also affected membrane IL-7R (mIL-7R) expression [10]; however, differences of mIL-7R expression on adaptive immune cell subsets between different IL7RA allele carriers were not found [11].…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐7‐dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes

et al. 2021

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The important role of IL‐7 in the generation of self‐reactive T‐cells in autoimmune diseases is well established. Recent studies on autoimmunity‐associated genetic polymorphisms indicated that differential IL‐7 receptor (IL‐7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL‐7‐mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL‐7‐mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t‐distributed Stochastic Neighbor‐Embedded (t‐SNE)‐analyses. IL‐7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL‐7, we detected lower monocyte IL‐7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL‐7 stimulation. t‐SNE analyses revealed IL‐7‐dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA‐DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL‐7 and CD40/IL‐7R co‐expression differed between patients and controls. This study shows the unique effects of IL‐7 on monocyte phenotype and functions. Lower IL‐7R expression on IL‐7‐induced CD40high monocytes and impaired IL‐7 response characterize monocytes from patients with type 1 diabetes.

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Interleukin-7 receptor α-chain haplotypes differentially affect soluble IL-7 receptor and IL-7 serum concentrations in children with type 1 diabetes

Cited by 8 publications

References 37 publications

Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

Higher Interleukin-7 serum concentrations in patients with cystic fibrosis correlate with impaired lung function

Interleukin‐7‐dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes

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