Soluble Adhesion Molecules in Preclinical Type 1 Diabetes

Toivonen, Anna; Kulmala, Petri; Savola, K.; Åkerblom, Hans K.; Knip, Mikael

doi:10.1203/00006450-200101000-00009

Cited by 20 publications

(19 citation statements)

References 45 publications

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“…Early studies suggested that L‐selectin could be one of the new risk markers for type 1 diabetes development in humans and animal models. Subsequent studies further suggested that elevated levels of sL‐selectin are associated with high titers of insulinoma‐associated protein 2 antibody in children with type 1 diabetes and siblings of diabetic children. Therefore, augmented sL‐selectin expression in patients can manifest an active destructive insulitis procedure.…”

Section: Neutrophil‐derived Effector Molecules and Type 1 Diabetesmentioning

confidence: 99%

Neutrophils in type 1 diabetes

Huang

Xiao

et al. 2016

J of Diabetes Invest

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Type 1 diabetes is an autoimmune disease that afflicts millions of people worldwide. It occurs as the consequence of destruction of insulin‐producing pancreatic β‐cells triggered by genetic and environmental factors. The initiation and progression of the disease involves a complicated interaction between β‐cells and immune cells of both innate and adaptive systems. Immune cells, such as T cells, macrophages and dendritic cells, have been well documented to play crucial roles in type 1 diabetes pathogenesis. However, the particular actions of neutrophils, which are the most plentiful immune cell type and the first immune cells responding to inflammation, in the etiology of this disease might indeed be unfairly ignored. Progress over the past decades shows that neutrophils might have essential effects on the onset and perpetuation of type 1 diabetes. Neutrophil‐derived cytotoxic substances, including degranulation products, cytokines, reactive oxygen species and extracellular traps that are released during the process of neutrophil maturation or activation, could cause destruction to islet cells. In addition, these cells can initiate diabetogenic T cell response and promote type 1 diabetes development through cell–cell interactions with other immune and non‐immune cells. Furthermore, relevant antineutrophil therapies have been shown to delay and dampen the progression of insulitis and autoimmune diabetes. Here, we discuss the relationship between neutrophils and autoimmune type 1 diabetes from the aforementioned aspects to better understand the roles of these cells in the initiation and development of type 1 diabetes.

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Section: Neutrophil‐derived Effector Molecules and Type 1 Diabetesmentioning

confidence: 99%

Neutrophils in type 1 diabetes

Huang

Xiao

et al. 2016

J of Diabetes Invest

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“…In our previous cross-sectional study we did not find any association between the levels of sICAM-1 and sL-selectin and HLA-DR-status [5]. Accordingly HLA-conferred predisposition to Type 1 diabetes hardly explains the differences in the concentrations of sICAM-1 between progressors and non-progressors observed among these autoantibodypositive siblings.…”

Section: Discussionmentioning

confidence: 54%

“…This could be due to the limited number of cases in each group, however. In our previous study we found an association between high titres of ICA and sICAM-1, and between IA-2A positivity and high concentrations of sICAM-1 and sL-selectin [5], whereas another survey did not show any association [4]. Despite contradictory findings it is still possible that the soluble adhesion molecules could reflect other characteristics of the autoimmmune process than conventional humoral immune markers.…”

Section: Discussionmentioning

confidence: 84%

“…So far the studies on the role of soluble adhesion molecules in Type 1 diabetes have been cross-sectional [2,3,4,5], and there are no data available on the dynamics of these molecules during pre-clinical diabetes. In this current work we evaluated whether serum concentrations of soluble ICAM-1 and L-selectin in autoantibody-positive siblings of diabetic children, when measured serially over a relatively long period of time, differed between those who progressed to clinical diabetes and those who remained non-diabetic, and assessed accordingly whether these biomarkers could be used to discriminate between disease progressors and non-progressors.…”

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confidence: 99%

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Soluble adhesion molecules in pre-clinical Type 1 diabetes: a prospective study

et al. 2003

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Aims. This prospective case-control study aimed at evaluating the time course of serum concentrations of soluble adhesion molecules; intercellular adhesion molecule-1 and L-selectin in siblings with signs of pre-clinical Type 1 diabetes in order to relate these concentrations to autoantibody status and to assess whether these markers could discriminate between those siblings who progressed to clinical diabetes and those who remained non-diabetic. Methods. Serum levels of soluble adhesion molecules were measured with enzyme-linked immunosorbent assays in autoantibody-positive initially healthy siblings of diabetic children who progressed to clinical disease during the observation period of 10 years and in sex-and age-matched autoantibody-positive siblings who have remained unaffected. Results. The intraindividual and interindividual variability in the concentrations of soluble adhesion molecules was conspicuous both among the progressors and nonprogressors. Integrated concentrations (area-under-the curve) of intercellular adhesion molecule-1 over a period of 6 to 48 months before the diagnosis was higher in the progressors (p=0.035), the difference being most evident 18 to 24 months before diagnosis (p=0.015). The integrated concentrations of soluble L-selectin were similar in progressors and non-progressors over the total pre-clinical period. There were no differences in the integrated concentrations of soluble adhesion molecules in relation to the initial or maximal number of autoantibodies detected during the follow-up. Conclusion/interpretation. These observations suggest that the process of destructive insulitis could be initiated approximately 4 years before the manifestation of clinical diabetes, being most active about 1.5 years before diagnosis. Peripheral concentrations of soluble intercellular adhesion molecule-1 or L-selectin are not helpful in the identification of those prediabetic subjects who will progress to clinical disease over the next 10 years, since there is substantial overlapping in these concentrations between progressors and nonprogressors. [Diabetologia (2003) 46:492-495] Keywords ICAM-1, L-selectin, autoantibodies, prediction, prospective. Corresponding author: M. Knip MD PhD, Hospital for Children and Adolescents, University of Helsinki, P.O. Box 281, 00029 HUCH, Helsinki, Finland E-mail: Mikael.Knip@hus.fi Abbreviations: GADA, antibodies to the 65 kD isoform of glutamic acid decarboxylase; IAA, insulin autoantibodies; IA-2A, antibodies to the protein tyrosine phosphatase-related IA-2 antigen; ICA, islet cell antibodies; ICAM-1, intercellular adhesion molecule-1; JDF, juvenile diabetes foundation; NOD mouse, non-obese diabetic mouse. Diabetologia (2003) 46:492-495

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“…The paper in this issue of Pediatric Research from the Childhood Diabetes in Finland Study Group adds to the evidence of increased levels of soluble adhesion molecules in type 1 diabetes (9). The authors present data on soluble ICAM-1 and L-selectin in a large and well-characterized group of subjects at high risk of developing diabetes.…”

mentioning

confidence: 98%

Measurement of Soluble Adhesion Molecules: Can It Improve Diabetes Prediction?: Commentary on the article by Toivonen et al. on page 24

Wherrett

2001

Pediatr Res

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Soluble Adhesion Molecules in Preclinical Type 1 Diabetes

Cited by 20 publications

References 45 publications

Neutrophils in type 1 diabetes

Neutrophils in type 1 diabetes

Soluble adhesion molecules in pre-clinical Type 1 diabetes: a prospective study

Measurement of Soluble Adhesion Molecules: Can It Improve Diabetes Prediction?: Commentary on the article by Toivonen et al. on page 24

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