scholarly journals Breastfeeding and circulating immunological markers during the first 3 years of life: the DIABIMMUNE study

Diabetologia ◽  
2021 ◽  
Author(s):  
Maija E. Miettinen ◽  
Jarno Honkanen ◽  
Sari Niinistö ◽  
Outi Vaarala ◽  
Suvi M. Virtanen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cd40 Ligand ◽  
Inflammation Markers ◽  
Serum Samples ◽  
Soluble Cd40 Ligand ◽  
Gut Inflammation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Immunological Markers ◽  
Inflammatory Protein

Abstract Aims/hypothesis Our aim was to study the association between duration of breastfeeding and circulating immunological markers during the first 3 years of life in children with HLA-conferred susceptibility to type 1 diabetes. Methods We performed a longitudinal analysis of 38 circulating immunological markers (cytokines, chemokines and growth factors) in serum samples from Finnish (56 individuals, 147 samples), Estonian (56 individuals 148 samples) and Russian Karelian children (62 individuals, 149 samples) at 3, 6, 12, 18, 24 and 36 months of age. We also analysed gut inflammation markers (calprotectin and human β defensin-2) at 3 (n = 96) and 6 months (n = 153) of age. Comparisons of immunological marker medians were performed between children who were breastfed for 6 months or longer vs children who were breastfed for less than 6 months. Results Breastfeeding for 6 months or longer vs less than 6 months was associated with lower median of serum immunological markers at 6 months (granulocyte-macrophage colony-stimulating factor [GMCSF], macrophage inflammatory protein [MIP-3α]), 12 months (IFN-α2, vascular endothelial growth factor, GMCSF, IFN-γ, IL-21), 18 months (FGF-2, IFN-α2) and 24 months of age (CCL11 [eotaxin], monocyte chemoattractant protein-1, TGFα, soluble CD40 ligand, IL-13, IL-21, IL-5, MIP-1α) (all p < 0.01) but not at 36 months of age. Breastfeeding was not associated with gut inflammation markers at 3 and 6 months of age. Conclusions/interpretation Children who were breastfed for 6 months or longer had lower medians for 14 immunological markers at one or more age points during the first 2 years of life compared with children who were breastfed for less than 6 months. The clinical meaning of the findings is not clear. However, the present study contributes to the understanding of immunological differences in children that have been breastfed longer, and thus provides a mechanistic suggestion for the previously observed associations between breastfeeding and risk of type 1 diabetes. Graphical abstract

scholarly journals Relationship Between Markers of Platelet Activation and Inflammation with Disease Activity in Wegener’s Granulomatosis

2011 ◽  
Vol 38 (6) ◽  
pp. 1048-1054 ◽  
Author(s):  
GUNNAR TOMASSON ◽  
MICHAEL LAVALLEY ◽  
KAHRAMAN TANRIVERDI ◽  
JAVIER D. FINKIELMAN ◽  
JOHN C. DAVIS ◽  
...  
Keyword(s):  
Disease Activity ◽  
Platelet Activation ◽  
Wegener’S Granulomatosis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Cd40 Ligand ◽  
Wegener's Granulomatosis ◽  
Soluble Cd40 Ligand ◽  
Monocyte Chemoattractant Protein 1 ◽  
Unit Increase ◽  
Active Disease

Objective.There remains a need for biomarkers to guide therapy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our objective was to determine whether measures of platelet activation or inflammation are associated with disease activity in Wegener’s granulomatosis (WG).Methods.Study subjects were participants in a clinical trial. Soluble CD40 ligand (sCD40L), C-reactive protein, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), P-selectin, vascular endothelial growth factor, and proteinase 3 (PR3)-specific ANCA were measured by ELISA using plasma samples obtained at baseline (active disease), at remission, and prior to, during, and after first flares. Disease activity was assessed by the Birmingham Vasculitis Activity Score for WG (BVAS/WG). Association of biomarkers with disease activity was determined with conditional logistic and linear regression.Results.Over a mean followup of 27 months, 180 subjects underwent 2044 visits; markers were measured in 563 samples. Longitudinally, all markers other than IL-6 were associated with disease activity. The strongest associations for active disease at baseline versus remission were observed for sCD40L (OR 4.72, 95% CI 2.47–9.03), P-selectin (OR 6.26, 95% CI 2.78–14.10), PR3-ANCA (OR 9.41, 4.03–21.99), and inversely for MCP-1 (OR 0.36, 95% CI 0.22–0.57). BVAS/WG increased by 0.80 (95% CI 0.44–1.16), 0.83 (95% CI 0.42–1.25), and 0.81 (95% CI 0.48–1.15) per unit-increase in PR3-ANCA, sCD40L, and P-selectin, respectively; and decreased by 1.54 (95% CI 0.96–2.12) per unit-increase in MCP-1.Conclusion.Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG.

scholarly journals Simultaneous Detection of Eight Analytes in Human Serum by Two Commercially Available Platforms for Multiplex Cytokine Analysis

2007 ◽  
Vol 15 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Gary Toedter ◽  
Karen Hayden ◽  
Carrie Wagner ◽  
Carrie Brodmerkel
Keyword(s):  
Simultaneous Detection ◽  
Tissue Level ◽  
Careful Examination ◽  
Serum Samples ◽  
Meso Scale Discovery ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Cytokine Analysis ◽  
Endothelial Growth Factor

ABSTRACT The accurate detection and quantitation of cytokines in serum are important in the study of disease mechanisms, pathogenesis, and treatment. Serum cytokines can reflect processes that are occurring at the cellular or tissue level and thus provide a means of indirectly monitoring these processes. Multiplex detection of cytokines allows the simultaneous measurement of multiple cytokines in a sample, increasing the efficiency of measuring the cytokines while reducing the serum sample volumes required for the testing. Two commercially available multiplex platforms were evaluated (Pierce SearchLight and Meso Scale Discovery), using multiplexes capable of simultaneously detecting eight cytokines. The cytokines analyzed in this study were gamma interferon, vascular endothelial growth factor, tumor necrosis factor alpha, interleukin-6 (IL-6), macrophage inflammatory protein 1β, monocyte chemoattractant protein 1, IL-12p40, and IL-4. The range of quantitation of the platforms, the recovery of spiked cytokines, and the detection of the cytokines in serum samples from subjects with ulcerative colitis, Crohn's disease, rheumatoid arthritis, and psoriasis were examined. The findings showed that the detection of the cytokines was highly dependent upon the platform, with the consistency of the detection of cytokines across platforms being dependent upon the cytokine being analyzed. A careful examination of platform assay performance must be made prior to utilizing multiplex platforms in a study. While some cytokines will give similar patterns of results across platforms, others will be highly variable. The use of the same platform within a study or across studies where data will be compared is advised.

Serum Levels of Soluble CD40 Ligand at Flare and at Remission in Patients with Systemic Lupus Erythematosus

2009 ◽  
Vol 36 (5) ◽  
pp. 953-960 ◽  
Author(s):  
MARIA URQUIZU-PADILLA ◽  
EVA BALADA ◽  
FINA CORTÉS ◽  
EDUARDO HERMOSILLA PÉREZ ◽  
MIQUEL VILARDELL-TARRÉS ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Cd40 Ligand ◽  
Biologically Active ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Soluble Cd40 Ligand ◽  
Group 4

Objective.To perform a prospective evaluation of soluble CD40 ligand (sCD40L) levels according to the activity of systemic lupus erythematosus (SLE).Methods.Two serum samples were taken from 53 patients with SLE: at flare and at remission. Clinical and biological measures (sCD40L levels were measured by a commercial ELISA) were evaluated in both situations.Results.Patients with SLE had significantly lower median levels of sCD40L during flare than during remission [3365 (6157) vs 7125 (4122) pg/ml; p < 0.001]. The multivariate analysis to explain those patients with lower values of sCD40L during flare than during remission included 3 variables: 2 related to flare (prednisone dose received ≤ 15 mg/day and platelet counts > 192,000 × 106/l) and one related to lower changes in SLE Disease Activity Index (SLEDAI) score. We regrouped patients with the 2 characteristics related to flare as Group 4, and the others were Group 123. All patients with low SLEDAI scores at flare had statistically significant lower sCD40L levels during flare than during remission. When flare SLEDAI scores were higher than the 50th percentile, patients of Group 123 showed the same behavior and even more diminished levels of sCD40L during flare than patients of Group 123 with low SLEDAI scores (p = 0.023); and patients of Group 4 showed no differences in the values of sCD40L between flare and remission (p = 0.241).Conclusion.sCD40L plays a biologically active role, with decreased levels at flare at low SLEDAI scores. At high SLEDAI scores there are mechanisms that involve platelets and that are inhibited by high doses of prednisone that lead to increased serum values of sCD40L at flare.

scholarly journals Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

2012 ◽  
Vol 210 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Qibin Zhang ◽  
Thomas L. Fillmore ◽  
Athena A. Schepmoes ◽  
Therese R.W. Clauss ◽  
Marina A. Gritsenko ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
C1 Inhibitor ◽  
Serum Samples ◽  
Healthy Control

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

scholarly journals Maternal Enterovirus Infection during Pregnancy as a Risk Factor in Offspring Diagnosed with Type 1 Diabetes between 15 and 30 Years of Age

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Elfving ◽  
Johan Svensson ◽  
Sami Oikarinen ◽  
Björn Jonsson ◽  
Per Olofsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Young Adulthood ◽  
Immunoglobulin M ◽  
Control Group ◽  
Enterovirus Infection ◽  
Group 14 ◽  
Serum Samples ◽  
Specific Immunoglobulin ◽  
Adolescence And Young Adulthood

Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM) antibodies and enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16%) were enterovirus IgM-positive, and 4/90 (4%) were positive for enterovirus RNA (n.s.). Boys of enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22–17.6), as compared to boys of IgM-negative mothers (P<.025). These results suggest that gestational enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.

Increased CD40 ligand and platelet–monocyte aggregates in patients with type 1 diabetes mellitus

2004 ◽  
Vol 176 (2) ◽  
pp. 321-325 ◽  
Author(s):  
S.A. Harding ◽  
A.J. Sommerfield ◽  
J. Sarma ◽  
P.J. Twomey ◽  
D.E. Newby ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Cd40 Ligand

scholarly journals Time-resolved Fluorometric Assay for Detection of Autoantibodies to Glutamic Acid Decarboxylase (GAD65)

2003 ◽  
Vol 49 (6) ◽  
pp. 908-915 ◽  
Author(s):  
Matti Ankelo ◽  
Annette Westerlund-Karlsson ◽  
Jorma Ilonen ◽  
Mikael Knip ◽  
Kaisa Savola ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glutamic Acid ◽  
Type 1 Diabetes Mellitus ◽  
Glutamic Acid Decarboxylase ◽  
Acid Decarboxylase ◽  
Serum Samples ◽  
Analytical Range ◽  
Radiobinding Assay

Abstract Background: Type 1 diabetes mellitus results from destruction of the pancreatic insulin-producing beta cells by a chronic autoimmune process. Methods are needed for the detection of circulating autoantibodies to glutamic acid decarboxylase (GAD65), a major marker of this process. Methods: Streptavidin-coated microtiter plates were incubated with biotinylated GAD65, and after incubation with serum samples from patients with type 1 diabetes mellitus and control individuals, europium-labeled GAD65 was added. After washing steps, the delayed fluorescence was measured in duplicate in a fluorometer. Samples collected from 100 patients with newly diagnosed type 1 diabetes mellitus and 100 healthy controls were measured by the new assay and by a radiobinding assay. Results: The detection limit of the new assay was 1.49 WHO units/mL, the calibration curve was linear to 4 140 WHO units/mL, and no hook effect was observed up to 41 400 WHO units/mL. The intraassay CV was 2.1–6.3% over the calibration range. For patient serum samples, the intraassay, interassay, and total CVs were 5.4–7.0%, 9.8–13%, and 12–14%, respectively. Compared with conventional radioimmunologic methods, the analytical range was broader and the analysis time required to perform the measurements was shorter. At a cutoff with 99% specificity, the new assay and the radiobinding assay were positive in 71 and 67 patients, respectively. Conclusions: The new assay provides a rapid and sensitive nonradioactive method applicable for large-scale screening for beta-cell autoimmunity. It has a broad linear analytical range, is easy to perform and automate, and has sensitivity and specificity comparable to those for the conventional radioisotope assay.

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