| 1. |
- Björck, Sara, et al.
(författare)
-
Serum cytokine pattern in young children with screening detected celiac disease.
- 2015
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 179:2, s. 230-235
-
Tidskriftsartikel (refereegranskat)abstract
- Celiac disease is an autoimmune disease characterized by inflammation localized to the small bowel, but less is known about systemic signs of inflammation. The aim was to measure cytokines of the T helper 1 (Th1) and T helper 2 (Th2) cell patterns in children with screening detected celiac disease before and after treatment with a gluten free diet.
|
|
| 2. |
|
|
| 3. |
- Lindehammer, Sabina, et al.
(författare)
-
Early human pregnancy serum cytokine levels predict autoimmunity in offspring.
- 2011
-
Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44, s. 445-452
-
Tidskriftsartikel (refereegranskat)abstract
- It is generally believed that pregnancy is mediated by a Th2 response, which includes cytokines that promote placental growth and are involved in inducing tolerance to the foetus. If the balance between Th1/and Th2-mediated cytokines is disrupted, systemic and local changes could predispose the foetus to future disease. Therefore, a shift in the Th1/Th2 balance during pregnancy, possibly caused by underlying environmental factors, could be associated with post-partum autoimmune disease in the offspring. Based on this presumption, we used celiac disease as a model to investigate whether autoimmunity is triggered in the foetus during early pregnancy, observed as changes in the mother's cytokine profile. Ten cytokines were measured by electro-chemi-luminescent multiplex ELISA in serum samples obtained from mothers during early pregnancy. Cases included women with children who had developed verified celiac disease before the age of 5, who were compared with other women as matched controls. We observed that 7 out of 10 cytokine levels were significantly increased in our case mothers when compared to controls. Five of these belonged to what is generally known as a Th1-mediated response (TNF?, IFN?, IL-2, IL-1? and IL-12) and two were Th2 cytokines (IL-13 and IL-10). However, the IL-10 cytokine is known to have features from both arms of the immune system. These results were confirmed in a logistic regression model where five out of the initial seven cytokines remained. This study suggests that increase in Th1 serum cytokines may be associated with celiac disease in offspring.
|
|
| 4. |
- Lindehammer, Sabina, et al.
(författare)
-
Early-Pregnancy Cytokines in Mothers to Children Developing Multiple, Persistent Islet Autoantibodies, Type 1 Diabetes, or Both Before 7 Years of Age.
- 2011
-
Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1600-0897 .- 1046-7408. ; 66, s. 495-503
-
Tidskriftsartikel (refereegranskat)abstract
- Citation Lindehammer SR, Fex M, Maziarz M, Hanson I, Marsal K, Lernmark Å on behalf of the Diabetes Prediction in Skåne (DiPiS) Study Group. Early-pregnancy cytokines in mothers to children developing multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age. Am J Reprod Immunol 2011 Problem Increased levels of serum cytokines in early pregnancy may increase the risk of type 1 diabetes in the offspring. Method of study Early-pregnancy (between 10 and 16 gestational weeks) serum samples from non-diabetic index mothers (n = 48) of children who developed islet autoimmunity, type 1 diabetes, or both before 7 years of age were analyzed for IFN-γ, IL-10, IL-12, IL-13, IL-1β, IL-2, IL-4, IL-5, CXCL8, and TNF. Control mothers (n = 93) were matched for age, sampling date, and HLA-DQ genotypes. Results IFN-γ (P = 0.02) and IL-1β (P = 0.04) were elevated in the index mothers. All cytokines except IL-4 were highly correlated (P < 0.0001). IFN-γ [OR 1.39 (1.04, 1.85), P = 0.026] and possibly IL-2 [OR 1.21 (0.99, 1.48), P = 0.057] in early pregnancy were associated with an increased risk of multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age in the offspring. However, the statistical significance for IL-2 was lost in the logistic regression when adjusted for gestational length at delivery and parity. Conclusion Increased Th1 cytokine levels during early pregnancy might contribute to an increased risk of islet autoimmunity, type 1 diabetes, or both in the offspring.
|
|
| 5. |
- Lindehammer, Sabina Resic, et al.
(författare)
-
Viruses, diabetes, and autoimmunity : Studies of subjects at genetic risk for type 1 diabetes
- 2013
-
Ingår i: Diabetes and Viruses. - New York, NY : Springer New York. - 9781461440505 - 9781461440512 ; 9781461440512, s. 187-194
-
Bokkapitel (refereegranskat)abstract
- The possible importance of virus infections before the development of islet autoimmunity and then for the appearance of clinical type 1 diabetes is reviewed. There is a lack of specific data on the role of virus to induce islet autoimmunity. There is also a paucity of data to demonstrate that virus infections may contribute to an accelerated disease process resulting in clinical onset of type 1 diabetes. In contrast, there is a plethora of studies on virus infections at the time of clinical onset. However, these studies have made the understanding of virus in type 1 diabetes less easy. Future studies need to address further gestational infections and the risk of the offspring for islet autoimmunity. Such studies should also investigate the mechanisms by which gestational infections may alter the ability of the offspring to respond to future virus infections related to the development of islet autoimmunity or accelerator of the clinical onset of diabetes.
|
|
| 6. |
- Lindehammer, Sabina, et al.
(författare)
-
Seroconversion to islet autoantibodies between early pregnancy and delivery in non-diabetic mothers
- 2011
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 1872-7603 .- 0165-0378. ; 88:1, s. 72-79
-
Tidskriftsartikel (refereegranskat)abstract
- Islet autoantibodies are currently used to classify type 1 diabetes at diagnosis as they reflect the autoimmune pathogenesis of the disease. The presence of maternal autoantibodies reactive with pancreatic islet antigens is thought to increase the risk for type 1 diabetes in the offspring. The objective of this study was to determine seroconversion to islet autoantibodies in non-diabetic mothers during pregnancy. Screening of 33,682 mothers between September 2000 and August 2004 in the Diabetes Prediction in Skane (DiPiS) study showed that at delivery, 242 non-diabetic mothers had increased titers of islet autoantibodies reactive with glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or insulin (IAA), alone or in combination. Control mothers (n = 1419), who were islet autoantibody negative at delivery, were randomly selected and matched by age, parity and pregnancy sampling date. Mothers positive for GADA (92%), IA-2A (84%) or IAA (65%) at delivery had increased titers already evident in early pregnancy. Titers declined for GADA (p<0.0001). IA-2A (p<0.0001) and IAA (p<0.0001). Seroconversion during pregnancy was observed for GADA in 10 (8%), IA-2A in 3 (16%) and IAA in 37 (35%) mothers. It is concluded that non-diabetic mothers with islet autoantibodies at delivery had significantly higher titers during early pregnancy than at delivery. As the statistical power in the seroconverting mothers was insufficient, further studies are needed to determine if the risk for type 1 diabetes in the offspring differs between mothers who already had increased titers of islet autoantibodies during early pregnancy or acquired them during pregnancy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
|
|
| 7. |
- Lindehammer, Sabina, et al.
(författare)
-
Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
-
Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
|
|
| 8. |
- Lindehammer, Sabina
(författare)
-
Triggers of autoimmunity. Studies on gestational events.
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective The primary aim of this thesis was to test whether gestational exposure to environmental factors may induce islet autoimmunity. The second aim was to determine to what extent the exposure to viruses or other environmental factors is a risk factor for type 1 diabetes in the offspring. As children with type 1 diabetes have a higher risk of developing celiac disease (CD), an additional aim was to determine whether markers of possible infections during early pregnancy was associated with development of tissue transglutaminase (tTG) autoantibodies or CD in the offspring. These aims have been summarized in four independent studies. Study population and Methods The Diabetes Prediction in Skåne (DiPiS) is a population based study where blood samples were obtained at the time of delivery between September 2000 and August 2004 from all mothers in this region (Skåne). The blood samples were analyzed for HLA-DQ alleles and islet autoantibodies. The prospective cohort study Celiac Disease Prediction in Skåne (CiPiS) is part of the DiPiS study, which aims to determine the etiology indicators of celiac disease (CD) in newborn children. Children with HLA-risk alleles associated with CD were screened for tissue transglutaminase autoantibodies (tTGA). CD was established by intestinal biopsy in children with confirmed tTGA. Early pregnancy serum samples (gestational week 10-16) were collected from the Southern Sweden Microbiological biobank (SSM-Biobank). This biobank contains more than 120,000 stored plasma samples that have been obtained between 1986 and 2009 from all pregnant mothers at their first visit to the Maternity Care Center. By combining the SSM-Biobank with DiPiS and CiPiS, a total of 24,000 mothers were identified. All mothers included in this thesis (n=1,748) were analyzed for HLA genotype, islet autoantibodies (GADA, IA-2A and IAA in both early pregnancy samples and at delivery), nine different cytokines, one chemokine (early pregnancy samples), IgM class enterovirus (EV) antibodies and EV-RNA (early pregnancy samples). Study I-IV Study I: The objective of our first study was to determine seroconversion to islet autoantibodies in non-diabetic mothers during pregnancy. This was achieved by analyzing end point titers of GADA, IA-2A and IAA in both early pregnancy samples and samples at delivery. Mother’s positive for GADA (92%), IA-2A (84%) or IAA (65%) at delivery had increased titers already in early pregnancy. Titers declined for GADA (p<0.0001), IA-2A (p<0.0001) and IAA (p<0.0001). Seroconversion during pregnancy was observed for GADA in 10 (8%), IA-2A in 3 (16%) and IAA in 37 (35%) mothers. Study II: In this study, we collected early pregnancy serum samples from mothers who later gave birth to children who developed high titers of tTGA or confirmed CD. We then measured an array of Th1/Th2 cytokines (nine cytokines and one chemokine) with the aim of investigating whether CD is triggered already in utero as denoted by quantitative changes in the mother’s cytokine profile. We observed that levels of seven out of ten cytokines were significantly increased in mothers who gave birth to children with CD when compared to controls. Study III: As studies have shown that unbalanced gestational cytokine profiles have been associated with maternal autoimmune disease, preeclampsia, and recurrent spontaneous abortions we analyzed in the present study cytokines in serum samples collected during early pregnancy from mothers who gave birth to children developing multiple, persistent islet autoantibodies, type 1 diabetes, or both, before seven years of age. We found that IFN-γ (p=0.02) and IL-1β (p=0.04) were elevated in the index mothers. All cytokines except IL-4 were highly correlated (p<0.0001). Study IV: Gestational EV infections have been associated with risk HLA-DR as well as with type 1 diabetes in the child. We analyzed enterovirus RNA (EV-RNA) and IgM (EV-IgM) in relation to type 1 diabetes HLA-DQ risk genotypes and to islet autoantibodies in non-diabetic mothers studied both in early pregnancy and at delivery. EV-IgM, but not EV-RNA was detected during early pregnancy in 12% (44/365) islet autoantibody positive mothers compared to 11% (156/1457) of the controls (p=n.s.). In early pregnancy, mothers with HLA-DQ 2/2 or 2/X genotypes showed, in adjusted logistic regression, an increased risk for islet autoantibodies (OR 1.85, 95% CI 1.34-2.54; p=0.001). EV-IgM was not associated with HLA-DQ in early pregnancy. However, after adjusting for parity, maternal age, year of birth and season of early pregnancy, early pregnancy EV-IgM combined with DQ2/2 or 2/X increased the risk for the mother to be positive for islet autoantibodies at delivery (OR 3.10, 95% CI 1.35-7.15; p=0.008). Conclusion From these studies we conclude that pregnant non-diabetic mothers with islet autoantibodies at delivery had significantly higher titers of autoantibodies during early pregnancy than at delivery. As the statistical power in the seroconverting mothers was insufficient, further studies are needed to determine if the risk for type 1 diabetes in the offspring differs between mothers who already had increased titers of islet autoantibodies during early pregnancy or acquired them during pregnancy. Moreover, we conclude that a shift in the Th1/Th2 mediated cytokine pattern during early pregnancy, possibly caused by viral infection may be associated with CD in the offspring. Furthermore, the results from study III suggest that increased levels of IFN-γ and possibly IL-2 during early pregnancy was associated with an increased risk for multiple, persistent islet autoantibodies, type 1 diabetes, or both, before seven years of age in the offspring. Our final study concludes that EV-IgM in early pregnancy increased the risk for islet autoantibodies at delivery in non-diabetic mothers who carry HLA-DQ 2/2 or 2/X type 1 diabetes risk genotypes.
|
|
| 9. |
- Löfroos, Ann-Britt, et al.
(författare)
-
Colorectal cancer-infiltrating T lymphocytes display a distinct chemokine receptor expression profile
- 2017
-
Ingår i: European Journal of Medical Research. - : Springer Science and Business Media LLC. - 0949-2321 .- 2047-783X. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: T lymphocytes exert important homeostatic functions in the healthy intestinal mucosa, whereas in case of colorectal cancer (CRC), infiltration of T lymphocytes into the tumor is crucial for an effective anti-tumor immune response. In both situations, the recruitment mechanisms of T lymphocytes into the tissues are essential for the immunological functions deciding the outcome. The recruitment of T lymphocytes is largely dependent on their expression of various chemokine receptors. The aim of this study was to identify potential chemokine receptors involved in the recruitment of T lymphocytes to normal human colonic mucosa and to CRC tissue, respectively, by examining the expression of 16 different chemokine receptors on T lymphocytes isolated from these tissues. Methods: Tissues were collected from patients undergoing bowel resection for CRC. Lymphocytes were isolated through enzymatic tissue degradation of CRC tissue and nearby located unaffected mucosa, respectively. The expression of a broad panel of chemokine receptors on the freshly isolated T lymphocytes was examined by flow cytometry. Results: In the normal colonic mucosa, the frequencies of cells expressing CCR2, CCR4, CXCR3, and CXCR6 differed significantly between CD4+ and CD8+ T lymphocytes, suggesting that the molecular mechanisms mediating T lymphocyte recruitment to the gut differ between CD4+ and CD8+ T lymphocytes. In CRC, the frequencies of cells expressing CCR2 and CXCR5 were significantly lower in both the CD4+ and CD8+ T lymphocyte populations compared to unaffected colonic mucosa, and the frequency of CCR9+ cytotoxic T lymphocytes was significantly decreased in CRC tissue. Conclusions: With regard to the normal gut mucosa, the results suggest that the molecular mechanisms mediating T lymphocyte recruitment differ between CD4+ and CD8+ T lymphocytes, which are important for understanding gut homeostasis. Importantly, T lymphocytes from CRC compared to normal colonic tissue displayed a distinct chemokine receptor expression profile, suggesting that mechanisms for recruitment of T lymphocytes to CRC tissue are skewed compared to normal colonic mucosa. Understanding these mechanisms could help in developing new strategies in cancer immunotherapy and to optimize already available alternatives such as immune checkpoint inhibitors.
|
|
| 10. |
- Rešić Lindehammer, Sabina, et al.
(författare)
-
Seroconversion to Islet Autoantibodies After Enterovirus Infection in Early Pregnancy.
- 2012
-
Ingår i: Viral Immunology. - : Mary Ann Liebert Inc. - 0882-8245 .- 1557-8976. ; 25:4, s. 254-261
-
Tidskriftsartikel (refereegranskat)abstract
- Gestational enterovirus (EV) infections have been associated with an increased risk for type 1 diabetes in the offspring. We therefore analyzed non-diabetic mothers for EV exposure in early pregnancy in relation to type 1 diabetes HLA-DQ risk genotypes and seroconversion to islet autoantibodies during pregnancy. Non-diabetic mothers who had islet autoantibodies (n=365) against glutamic acid decarboxylase (GADA), islet antigen-2 autoantibodies (IA-2A), or insulin autoantibodies (IAA), in early pregnancy and at delivery were compared to islet autoantibody-negative mothers (n=1457) matched for age and sampling date. Mothers were genotyped for HLA-DQ and analyzed for both EV-RNA and EV-IgM. EV-IgM, but not EV-RNA, was detected during early pregnancy in 12% of islet autoantibody-positive mothers compared to 11% of the controls. In early pregnancy, mothers with HLA-DQ 2/2 or 2/X genotypes showed an increased risk for islet autoantibodies at delivery (OR 1.85; p=0.001). After adjusting for parity, maternal age, year of birth, and season of early pregnancy, early pregnancy EV-IgM combined with DQ2/2 or 2/X increased the risk for islet autoantibodies (OR 3.10; 95% CI 1; p=0.008). EV-IgM in early pregnancy increased the risk for islet autoantibodies at delivery in non-diabetic mothers with HLA-DQ 2/2 or 2/X type 1 diabetes risk genotypes.
|
|
