Decreased serum level of IL-7 in patients with active Graves’ disease

Motylewska, Ewelina; Nieć, Martyna; Siejka, Agnieszka; Komorowski, Jan; Ławnicka, Hanna; Świętosławski, Jacek; Stępień, H

doi:10.1016/j.cyto.2015.04.020

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…Novel cytokines and chemokines, such as CXCL10 were reported to be related to pathogenesis of GD (64). Increased serum levels of IL-21 (65) and decreased serum IL-7 (66) were also reported in GD. Intriguingly, an association of chromosome 5q23–q33 with AITD suggested an important role of clustered cytokines and other immune modulators encoded in this genetic locus (67).…”

Section: Role Of Cytokines/chemokinesmentioning

confidence: 89%

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

2016

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Graves’ disease (GD) is an organ-specific autoimmune disease, and thyrotropin (TSH) receptor (TSHR) is a major autoantigen in this condition. Since the extracellular domain of human TSHR (TSHR-ECD) is shed into the circulation, TSHR-ECD is a preferentially immunogenic portion of TSHR. Both genetic factors and environmental factors contribute to development of GD. Inheritance of human leukocyte antigen (HLA) genes, especially HLA-DR3, is associated with GD. TSHR-ECD protein is endocytosed into antigen-presenting cells (APCs), and processed to TSHR-ECD peptides. These peptide epitopes bind to HLA-class II molecules, and subsequently the complex of HLA-class II and TSHR-ECD epitope is presented to CD4+ T cells. The activated CD4+ T cells secrete cytokines/chemokines that stimulate B-cells to produce TSAb, and in turn hyperthyroidism occurs. Numerous studies have been done to identify T- and B-cell epitopes in TSHR-ECD, including (1) in silico, (2) in vitro, (3) in vivo, and (4) clinical experiments. Murine models of GD and HLA-transgenic mice have played a pivotal role in elucidating the immunological mechanisms. To date, linear or conformational epitopes of TSHR-ECD, as well as the molecular structure of the epitope-binding groove in HLA-DR, were reported to be related to the pathogenesis in GD. Dysfunction of central tolerance in the thymus, or in peripheral tolerance, such as regulatory T cells, could allow development of GD. Novel treatments using TSHR antagonists or mutated TSHR peptides have been reported to be effective. We review and update the role of immunogenic TSHR epitopes and HLA in GD, and offer perspectives on TSHR epitope specific treatments.

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Section: Role Of Cytokines/chemokinesmentioning

confidence: 89%

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

2016

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“…IL‐7 is a cytokine that is known to influence lymphocyte differentiation, dimerize with hepatocyte growth factor to form a B cell growth–stimulating factor, and play a major role in B cell maturation and lymphoid cell survival . It has previously been studied as a potential biomarker for graft‐versus‐host disease , and potentially Graves’ disease . IL‐7 has also been shown to be dysregulated in SLE patients at the messenger RNA level and has been studied as a potential treatment option to correct dysregulated apoptosis in SLE B cells .…”

Section: Discussionmentioning

confidence: 99%

“…IL‐7 has also been shown to be dysregulated in SLE patients at the messenger RNA level and has been studied as a potential treatment option to correct dysregulated apoptosis in SLE B cells . IL‐7 is also a critical cytokine for T cell development, survival, and homeostasis, including T cell memory homeostasis . To date, no other studies have explored the use of IL‐7 as a serum or urinary biomarker for SLE or LN.…”

Section: Discussionmentioning

confidence: 99%

Identification of Low‐Abundance Urinary Biomarkers in Lupus Nephritis Using Electrochemiluminescence Immunoassays

Stanley

Mok

Vanarsa

et al. 2019

Arthritis & Rheumatology

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Objective. To investigate the utility of a sensitive platform using electrochemiluminescence (ECL) for the identification of low-abundance urinary protein biomarkers in lupus nephritis (LN).Methods. Forty-eight urine samples were obtained from subjects in 2 independent cohorts, each consisting of 3 groups (matched for age, sex, and race) of 8 patients with active LN (renal Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] >0), 8 patients with inactive SLE (renal SLEDAI 0), and 8 healthy controls. Samples were tested using a preexisting 40-plex ECL panel. A custom 5-plex ECL panel was then developed for further validation studies and used to test 140 urine samples (from 44 patients with active LN, 41 patients with inactive SLE, 28 healthy controls, and 27 patients with other kidney diseases).Results. Levels of 17 urinary proteins were elevated (P < 0.05 by 2-tailed Mann-Whitney U test) in samples from patients with active LN compared to samples from patients with inactive SLE and healthy controls in cohort 1, while 9 were similarly elevated in cohort 2. Of these, interleukin-7 (IL-7), IL-12p40, IL-15, interferonγ-inducible protein 10 (IP-10), and thymus and activation-regulated chemokine (TARC) were chosen for further validation. These 5 proteins were undetectable by enzyme-linked immunosorbent assay (ELISA). Hence, a custom 5-plex ECL panel was developed and used to validate the results from the initial 40-plex screening panel. Urinary IL-7, IL-12p40, IL-15, IP-10, and TARC levels were again significantly elevated in patients with active LN compared to those with inactive SLE and healthy controls, and correlated well with the renal SLEDAI and physician's global assessment of disease activity (R > 0.67, P < 0.05). All 5 urinary proteins were more frequently elevated in LN compared to controls with other chronic kidney diseases, although overall group differences attained significance only for urinary IL-7 and IL-15.Conclusion. Urinary levels of IL-7, IL-12p40, IL-15, IP-10, and TARC are potentially useful diagnostic tools in LN. The use of ECL assays may allow detection of urinary biomarkers that are below ELISA detection limits. ECL ASSAYS FOR LOW-ABUNDANCE BIOMARKERS IN LUPUS NEPHRITIS| 745 and others (6) are revolutionizing biomarker discovery, allowing researchers to screen for new biomarkers in an unbiased manner. These new technologies vary in sensitivity and cannot handle the high-volume sample throughput needed for subsequent biomarker validation studies or routine clinical diagnostics.Newer technologies have attempted to reduce the levels of background noise seen in a traditional enzyme-linked immunosorbent assay (ELISA) or antibody-based arrays by replacing an enzymatic-based detection signal with an alternative signal. One of the most promising techniques is the use of an electrode-coupled immunoassay with an electrochemiluminescent (ECL) signal. In this arrangement, the capture antibody is coupled to an electrode, and the detection antibody is labeled with a tag that emits a chemiluminescent...

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“…IL-7 was shown to be important for lymphoid cell survival and it plays a part in the development of T and B cells. It binds to hepatocyte growth factor to serve as a B cell growth stimulating factor [ 27 ]. Previous studies introduced IL-7 antibodies into non-obese diabetic mice and results appeared to reverse the disease [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of the link between in utero exposure to 2-aminoanthracene (2AA) and type-1 diabetes (T1D)

Mays

Hunter

Yau

et al. 2017

J Diabetes Metab Disord

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BackgroundA recent diabetes report revealed an increased incidence in diabetes including type 1-diabetes (T1D). The increase in the numbers of T1D incidences are thought to be related to environmental reasons such as the exposure to environmental chemicals including arylamine 2-aminoanthracene (2AA). T1D is an autoimmune disease of the pancreatic islet in which insulin-producing beta cells are destroyed by auto-reactive T-cells and monocytic cells.MethodsThe purpose of this study is to examine the extent to which 2AA exposure contributes to T1D. Three groups of pregnant Sprague Dawley dams ingested various concentrations of dietary 2AA from gestation through the postnatal period. A select number of cytokines and adipokines previously noted to play a significant role in inflammatory response were analyzed in the pancreas of the pups for alteration. The anatomy of the pancreas was also evaluated to determine any histological changes.ResultsResults showed over-expression of pro-inflammatory protein IL-6. Up-regulation of humoral genes IL-7 and IL-21 were also noted. Pathologic characterization showed no significant changes. Moreover, serum total protein was significantly reduced in exposed groups. Elevated serum glucose concentration seems to correspond to slightly lower insulin levels in serum. Cumulative neonatal weight gain analysis showed no major alterations between the control and gestationally-exposed rats.ConclusionIt appears that systemic effects of 2AA ingestion were mild in the neonates. Further assessments of pups who lived longer than two weeks could be a useful way to measure the progression and possibly further support our hypothesis that 2AA can lead to systemic effects that are indicative of inducing T1D.

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Decreased serum level of IL-7 in patients with active Graves’ disease

Cited by 5 publications

References 45 publications

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

Identification of Low‐Abundance Urinary Biomarkers in Lupus Nephritis Using Electrochemiluminescence Immunoassays

Assessment of the link between in utero exposure to 2-aminoanthracene (2AA) and type-1 diabetes (T1D)

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