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Vaarala, Outi
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Publications (10 of 80) Show all publications
Wahlberg, J., Waarala, O. & Ludvigsson, J. (2011). Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children. Pediatric Diabetes, 12(7), 604-610
Open this publication in new window or tab >>Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children
2011 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 12, no 7, p. 604-610Article in journal (Refereed) Published
Abstract [en]

A dominance of Th2 cytokine pattern is associated with allergic diseases, whereas a Th1 pattern has been reported in autoimmune type 1 diabetes (T1D). The Th1/Th2 paradigm has led to the interest in the relationship between these diseases. To investigate the association between atopic diseases, asthma and occurrence of T1D-related β-cell autoantibodies in children, we studied 7208 unselected 2.5-yr-old children from the All Babies in Southeast Sweden (ABIS) cohort. The ABIS cohort includes 17 055 (78.3% out of all 21 700) children born from October 1997 to October 1999, and followed prospectively with regular biological samples and questionnaires, at birth, at 1 and 2.5 yr. Risk factors for development of β-cell autoantibodies at the age of 2.5 yr were type of domiciliary, domestic animals (cat and dog) and getting a new brother/sister during first year of life. Maternal smoking during pregnancy [odds ratio (OR) 1.6] and heavy smoking at home (>10 vs. ≤10 cigarettes) implied risk for tyrosine phosphatase autoantibodies (IA-2A) (OR 2.9). Wheezing during the first year of life implied risk for glutamic acid decarboxylase autoantibodies (GADA) (OR 1.9) and double positivity for GADA and IA-2A (OR 9.1). Rash on several locations (at least three times during 12 months) (OR 1.7) as well as allergic symptoms related to fur-bearing animals (OR 2.7) implied risk for IA-2A. Food allergy against egg, cow-milk, fish, nuts/almonds (one or in combination) implied risk for GADA and IA-2A (OR 4.5). In a regression model wheezing during first year of life remained as a risk factor for GADA [OR 2.0, confidence interval (CI) 1.1–3.8; p = 0.031] and both GADA and IA-2A (OR 10.7, CI 3.9–29.4; p = 0.000). We conclude that allergic symptoms are associated with the development of T1D-related autoantibodies during the first years of life.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing, 2011
Keywords
asthma; allergy; GADA; IA-2A; T1D
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76272 (URN)10.1111/j.1399-5448.2011.00758.x (DOI)000296345600003 ()1466648 (PubMedID)
Available from: 2012-04-01 Created: 2012-04-01 Last updated: 2017-12-07Bibliographically approved
Lahdenperä, A., Ludvigsson, J., Fälth-Magnusson, K., Högberg, L. & Vaarala, O. (2011). The effect of gluten-free diet on Th1--Th2--Th3-associated intestinal immune responses in celiac disease. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 46(5), 538-549
Open this publication in new window or tab >>The effect of gluten-free diet on Th1--Th2--Th3-associated intestinal immune responses in celiac disease
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2011 (English)In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 46, no 5, p. 538-549Article in journal (Refereed) Published
Abstract [en]

Objective. To study T-helper (Th)1--Th2--Th3 gene activation profile in the small intestine and peripheral blood of children with celiac disease (CD) with special interest in the response to the gluten-free diet (GFD) treatment in order to elucidate an immune dysregulation not triggered by gluten. Material and methods. Small intestinal biopsies and venous blood were taken from seven children with CD (mean age: 8 years, four girls) at presentation and after 1 year of strict GFD. The Th1--Th2--Th3 gene expression profile was examined by real-time PCR arrays. The findings were compared with the corresponding expressions in peripheral blood and small intestinal biopsies from six reference children without CD (mean age: 6 years, four girls). Results. The Th1 gene expression profile including interferon (IFN)-gamma gamma, signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF) 1 together with reduced interleukin (IL)-2 expression was pronounced in small intestinal biopsies from children with untreated CD. A downregulation of IFN-gamma gamma transcripts was seen after 1 year of GFD, but there was still increased expression of STAT1 and IRF1 in association with low IL-2 expression in spite of eliminated exposure to wheat gluten. By contrast, the decreased intestinal expression of Th2 gene markers observed at presentation was normalized with GFD. The alterations in the mucosal gene expression profile were not reflected in peripheral blood. Conclusion. The GFD did not correct the increased activation of the IFN-gamma gamma signaling pathway related markers and reduced IL-2 expression, suggesting that they represent an immune dysregulation not dependent on gluten exposure.

Place, publisher, year, edition, pages
Informa Healthcare, 2011
Keywords
Arrays, biopsies, celiac disease, children, gene expression, gluten-free diet, PBMC, Th1, Th2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67826 (URN)10.3109/00365521.2011.551888 (DOI)000289437200005 ()
Available from: 2011-04-29 Created: 2011-04-29 Last updated: 2014-11-11
Piirainen, L., Haahtela, S., Helin, T., Korpela, R., Haahtela, T. & Vaarala, O. (2008). Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the saliva of patients with birch pollen allergy. Annals of Allergy, Asthma & Immunology, 100(4), 338-342
Open this publication in new window or tab >>Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the saliva of patients with birch pollen allergy
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2008 (English)In: Annals of Allergy, Asthma & Immunology, ISSN 1081-1206, E-ISSN 1534-4436, Vol. 100, no 4, p. 338-342Article in journal (Refereed) Published
Abstract [en]

Background: Lactobacillus rhamnosus GG (LGG) has demonstrated promising results in the treatment and prevention of atopic eczema.

 

 

Objective: To study the effects of LGG on the oral immune response in adolescents and adults with birch pollen allergy combined with oral allergy syndrome.

 

 

Methods: Patients received either LGG (n = 19) or a placebo (n = 19) for 5.5 months (from February 8 to August 6, 1999), starting 2.5 months before the birch pollen season. An oral apple challenge test was performed before, during, and after the pollen season. Saliva samples were collected before and after the challenges, and serum samples were collected before the challenges. Total IgA, IgG, and IgM and rBet v1 and rMal d1 specific IgA, IgG, IgG1, and IgG4 levels were measured from saliva with an enzyme-linked immunosorbent assay (ELISA). Serum rBet v1 specific IgE ELISA and birch radioallergosorbent testing were performed.

 

 

Results: After 5.5 months, rBet v1 and rMal d1 specific IgA levels had increased from baseline in the LGG compared with the placebo group (Δ rBet v1 IgA, 0.319 vs −0.136 relative units; P = .02; Δ rMal d1 IgA, 0.097 vs −0.117, P = .02). rBet v1 specific IgE serum levels did not differ between the groups. In the LGG group, rBet v1 specific IgE levels correlated positively with stimulated total IgA (P = .04) and IgG (P = .003) in saliva. In the placebo group, rBet v1 specific IgE levels correlated negatively with stimulated rBet v1 and rMal d1 IgA levels (P = .009 for both) and IgG (P = .02 and P = .03, respectively).

 

 

Conclusion: LGG showed immunostimulating effects on oral mucosa seen as increased allergen specific IgA levels in saliva.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42376 (URN)63340 (Local ID)63340 (Archive number)63340 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Ludvigsson, J., Faresjö, M., Hjorth, M., Axelsson, S., Chéramy, M., Pihl, M., . . . Casas, R. (2008). GAD treatment and insulin secretion in recent-onset type 1 diabetes. New England Journal of Medicine, 359(18), 1909-1920
Open this publication in new window or tab >>GAD treatment and insulin secretion in recent-onset type 1 diabetes
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2008 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 359, no 18, p. 1909-1920Article in journal (Refereed) Published
Abstract [en]

Background: The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods: We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results: Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (-0.21 vs. -0.27 nmol per liter [-0.62 vs. -0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (-0.72 vs. -1.02 nmol per liter per 2 hours [-2.20 vs. -3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions: GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.) Copyright © 2008 Massachusetts Medical Society. All rights reserved.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-43464 (URN)10.1056/NEJMoa0804328 (DOI)73922 (Local ID)73922 (Archive number)73922 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Marschan, E., Honkanen, J., Kukkonen, K., Kuitunen, M., Savilahti, E. & Vaarala, O. (2008). Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with igE sensitization. Pediatric Allergy and Immunology, 19(2), 132-139
Open this publication in new window or tab >>Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with igE sensitization
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2008 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 19, no 2, p. 132-139Article in journal (Refereed) Published
Abstract [en]

Risk of allergic diseases has been linked to abnormal patterns of fetal immune development, suggesting that priming of the immune system may occur in utero. The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells (CBMC) shows association with allergic diseases and IgE sensitization at 2 yr of age, and to study the effect of maternal probiotic supplementation on CBMC immune responses. CBMC were isolated from 98 neonates in a randomized double-blinded intervention study. CBMC were stimulated with beta-lactoglobulin, and phytohemaglutinin (PHA). Secretion of interferon-gamma (IFN-γ), interleukin-5 (IL-5), and IL-13 was measured by an ELISA; IL-2, IL-4, and IL-10 by a cytokine bead assay. T-cell polarization-associated IL-4 receptor and IL-12R expressions, and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR. The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age, and with the maternal probiotic or placebo supplementation. PHA-stimulated GATA-3 expression and IL-2 secretion in CBMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized, non-allergic children (p = 0.03 and 0.026). PHA-induced expression of GATA-3 correlated with IL-5 (p = 0.003, r = 0.300) and IL-13 (p = 0.007, r = 0.278) secretion of CBMC, and IL-5 secretion of β-lactoglobulin-stimulated CBMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized, non-allergic children (p = 0.013). Probiotic bacteria had no effect on CBMC immune responses. In CBMC-enhanced induction of GATA-3, which activates several Th2 cytokines genes, was a risk factor for IgE sensitization. The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens.

Keywords
allergic disease, cod blood, GATA-3, IL-5, sensitization
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42368 (URN)10.1111/j.1399-3038.2007.00593.x (DOI)63219 (Local ID)63219 (Archive number)63219 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Tiittanen, M., Westerholm-Ormio, M., Verkasalo, M., Savilahti, E. & Vaarala, O. (2008). Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes. Clinical and Experimental Immunology, 152(3), 498-507
Open this publication in new window or tab >>Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes
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2008 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 152, no 3, p. 498-507Article in journal (Refereed) Published
Abstract [en]

Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-β, interferon (IFN)-γ, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. The numbers of FoxP3- and CD25-expressing cells were studied with immunohistochemistry. Enhanced intestinal expressions of FoxP3, IL-10 and IFN-γ mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, <0.001). In potential CD, only the expression of IFN-γ mRNA was increased. The numbers of FoxP3-expressing cells were higher in active and potential CD (P < 0.001, P = 0.05), and the ratio of FoxP3 mRNA to the number of FoxP3-positive cells was decreased in potential CD when compared with controls (P = 0.007). The ratio of IFN-γ to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). Patients with T1D had no changes in regulatory T cell markers, but showed increased expression of IL-18 mRNA. The impaired up-regulation of FoxP3 transcripts despite the infiltration of FoxP3-positive cells in potential CD may contribute to the persistence of inflammation. The increased ratio of IFN-γ to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. The increased intestinal expression of IL-18 mRNA in patients with T1D adds evidence in favour of the hypothesis that T1D is associated with derangements in the gut immune system. © 2008 The Author(s).

Keywords
coeliac disease, FoxP3, gut, regulatory T cells, type 1 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42394 (URN)10.1111/j.1365-2249.2008.03662.x (DOI)63564 (Local ID)63564 (Archive number)63564 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Lundberg, A., Andersson Wikberg, L., Ilonen, J., Vaarala, O. & Böttcher (Fagerås), M. (2008). Lipopolysaccharide-Induced Immune Responses in Relation to the TLR4(Asp299Gly) Gene Polymorphism. Clinical and Vaccine Immunology, 15(12), 1878-1883
Open this publication in new window or tab >>Lipopolysaccharide-Induced Immune Responses in Relation to the TLR4(Asp299Gly) Gene Polymorphism
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2008 (English)In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 15, no 12, p. 1878-1883Article in journal (Refereed) Published
Abstract [en]

Altered microbial exposure is a possible explanation for the increase of allergies in the Western world. However, genetic factors influence microbially induced immune responses. We have investigated the TLR4(Asp299Gly) gene polymorphism and its possible association with receptor expression of circulating peripheral blood monocytes and the in vitro cytokine responses and phosphorylation of intracellular signaling proteins in peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) from Escherichia coli and Salmonella enterica serotype Typhimurium. We studied 34 of the predominant haplotype TLR4 Asp299 (AA) and 8 heterozygote Asp299Gly (AG) individuals. TLR4 expression levels were similar in the two genotype groups. Serovar Typhimurium LPS induced interleukin-12p70 from PBMC, and the degree of phosphorylation of the intracellular signaling protein I kappa B alpha in PBMC was lower in the AG than the AA group (P = 0.03 and P = 0.04, respectively). These results were not seen, however, when PMBC were stimulated with E. coli-derived LPS. Based on these results, we propose that TLR4(Asp299Gly) gene polymorphism and the bacterial origin of LPS should be considered when environmental LPS exposure is evaluated in disease risk or protection.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16220 (URN)10.1128/CVI.00241-08 (DOI)
Available from: 2009-01-12 Created: 2009-01-09 Last updated: 2017-10-31Bibliographically approved
Honkanen, J., Skarsvik, S., Knip, M. & Vaarala, O. (2008). Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T-cells from children with type 1 diabetes. Diabetes/Metabolism Research Reviews, 24(8), 635-641
Open this publication in new window or tab >>Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T-cells from children with type 1 diabetes
2008 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 24, no 8, p. 635-641Article in journal (Refereed) Published
Abstract [en]

Background

Type 1 diabetes (T1D) is characterised by loss of tolerance to beta-cell antigens, and the insulin-producing beta-cells in the pancreatic islets are destroyed by the host's own immune system. Immunological risk factors associated with T1D are related to the defects in the polarization of T-cells and in the function of regulatory T (Treg)-cells. We set out to study whether an impaired induction of regulatory mechanisms during the generation of T-cell responses upon stimulation is associated with T1D.

Methods

Naive T-cells were isolated from 18 children with recent T1D (0–14days from diagnosis; mean age 9.3 years), 11 children who had had T1D for at least 1 year (mean age 10.6) and 14 non-diabetic children (mean age 8.1). CD45RA+ T-cells were stimulated with PHA for 72 h in type 1 cytokine [interleukin (IL)-12 and anti-IL-4] or type 2 cytokine (IL-4 and anti-IL-12) environment. T-cell polarization and regulation related markers were analysed by quantitative reverse transcription polymerase chain reaction (QRT-PCR) (Th1 promoting T-bet, Th2 promoting GATA-3 and regulation related FOXP3, ICOS and NFATc2).

Results

Children with recently diagnosed T1D showed decreased induction of FOXP3, ICOS and NFATc2 in T-cells activated in type 1 cytokine milieu (p = 0.007, p = 0.001, and p = 0.02), whereas no differences between the diabetic and healthy children were seen in the up-regulation of activation markers, T-bet and GATA-3.

Conclusions

The poor induction of factors that mediate down-modulation of T-cell responses upon stimulation in type 1 cytokine environment may contribute to the development of autoreactive type 1 responses in T1D.

Keywords
type 1 diabetes, T helper cells, regulatory T-cell, naive T-cell, quantitative RT-PCR
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16217 (URN)10.1002/dmrr.904 (DOI)
Available from: 2009-01-12 Created: 2009-01-09 Last updated: 2017-12-14Bibliographically approved
Gullstrand, C., Wahlberg Topp, J., Ilonen, J., Vaarala, O. & Ludvigsson, J. (2008). Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study. Pediatric Diabetes, 9(3 PART 1), 182-190
Open this publication in new window or tab >>Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study
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2008 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, no 3 PART 1, p. 182-190Article in journal (Refereed) Published
Abstract [en]

Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42864 (URN)10.1111/j.1399-5448.2008.00369.x (DOI)69621 (Local ID)69621 (Archive number)69621 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Aittoniemi, J., Turpeinen, H., Tiitanen, M., Knip, M., Simell, O., Ilonen, J. & Vaarala, O. (2008). Relation among mannose-binding lectin 2 genotype, β-cell autoantibodies, and risk for type 1 diabetes in Finnish children. Human Immunology, 69(2), 108-111
Open this publication in new window or tab >>Relation among mannose-binding lectin 2 genotype, β-cell autoantibodies, and risk for type 1 diabetes in Finnish children
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2008 (English)In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 69, no 2, p. 108-111Article in journal (Refereed) Published
Abstract [en]

Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial. We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of β-cell autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the biallelic variant genotype reflecting total MBL deficiency tested positive more frequently for ≥3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28, p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D. The association of the biallelic variant genotype with positivity for multiple autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency. © 2008 American Society for Histocompatibility and Immunogenetics.

Keywords
b-cell autoantibodies, Mannose-binding, lectin, Type 1 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42374 (URN)10.1016/j.humimm.2008.01.007 (DOI)63320 (Local ID)63320 (Archive number)63320 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
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