| 11. |
- 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.
|
|
| 12. |
|
|
| 13. |
- Persson, Marie, et al.
(författare)
-
Immunological status in patients undergoing in vitro fertilisation : responses to hormone treatment and relationship to outcome
- 2012
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 96:1-2, s. 58-67
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to prospectively investigate the paternal antigen-induced cytokine secretion by peripheral blood mononuclear cells (PBMCs) in response to hormone treatment in women undergoing in vitro fertilisation (IVF) and to examine the predictive value of the cytokine secretion profile in the outcome of IVF treatment, in a pilot study. Twenty-five women were included and IVF treatment was successful for six and unsuccessful for 19 women. Blood samples were collected before IVF treatment, on four occasions during IVF and four weeks after embryo transfer. The numbers of Th1-, Th2- and Th17-associated cytokine-secreting cells and cytokine levels in cell supernatants were analysed by enzyme-linked immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex assay. None of the cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of the cytokines reached their peak levels at ovum pick-up, suggesting an enhancing influence of the hormonal stimulation. Pregnancy was associated with a high number of IL-4-, IL-5- and IL-13-secreting cells four weeks after ET. In conclusion, the results do not support our hypothesis of a more pronounced peripheral Th1 and Th17 deviation towards paternal antigens in infertile women with an unsuccessful IVF outcome, although this is based on a small number of observations. A larger study is required to confirm this conclusion. Higher numbers of Th2-associated cytokine-secreting cells in pregnant women four weeks after ET do corroborate the hypothesis of a Th2 deviation during pregnancy.
|
|
| 14. |
- Persson, Marie, et al.
(författare)
-
Reduced IFN-γ and IL-10 responses to paternal antigens during and after pregnancy in allergic women
- 2012
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 95:1-2, s. 50-58
-
Tidskriftsartikel (refereegranskat)abstract
- Normal pregnancy and allergy are both characterized by a T helper (Th) 2 deviation. In the current study, we hypothesized that paternal antigen-induced cytokine responses during pregnancy would be deviated toward Th2 and an anti-inflammatory profile, and that the Th2 deviation would be more pronounced in allergic pregnant women. Blood samples were collected longitudinally on three occasions during pregnancy and two occasions post partum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Twelve women fulfilled the criteria for allergy (allergic symptoms and circulating immunoglobulin [Ig] E antibodies to inhalant allergens) and 20 were non-allergic (nonsensitized without symptoms). The levels of Th1- and Th2-associated cytokines and chemokines, the Th17 cytokine IL-17 and the anti-inflammatory cytokine IL-10 of the groups were compared. Paternal antigen-induced IL-4 and IL-10 responses increased between the first and the third trimester. Allergy was associated with decreased paternal antigen-induced IFN-γ and CXCL10 secretion in the nonpregnant state (one year pp) and also decreased IFN-γ/IL-4 and IFN-γ/IL-13 ratios during pregnancy. We also observed a decreased paternal antigen-induced IL-10 response in allergic compared with non-allergic women during pregnancy, along with a decreased IL-10/IL-13 ratio. In conclusion, our findings support the hypothesis of lower Th1 responses toward paternal antigens in allergic than in non-allergic women, but also indicate that allergy is associated with a lower capacity to induce anti-inflammatory IL-10 responses after paternal antigen stimulation during pregnancy.
|
|
| 15. |
- Rodriguez-Martinez, Heriberto, et al.
(författare)
-
Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow
- 2010
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 84:1, s. 57-65
-
Tidskriftsartikel (refereegranskat)abstract
- Seminal plasma (SP) is a complex fluid which exerts biological actions in the female reproductive tract. In pigs, SP elicits endometrial inflammation and consequent immune changes after mating. This study tested whether heparin-binding spermadhesins (HBPs) and the heterodimer of porcine sperm adhesions I and II (PSP-I/PSP-II) in SP recruit different lymphocyte subsets (CD2(+), CD4(+) and CD8(+) T cells) or polymorphonuclear leukocytes (PMNs) to the superficial endometrium or luminal epithelium and lumen, respectively, of oestrous sows. In Experiment 1, endometrial biopsies were taken between 2 and 120 min after infusion of uterine horns with HBPs, PSP-I/PSP-II or saline and evaluated by immunohistochemistry or histology. In Experiment 2, the uterus of oestrous sows was infused with PSP-I/PSP-II or saline to assess PMN numbers in the uterine lumen 3 h later. PSP-I/PSP-II elicited CD2(+) T cell recruitment from 10 min, and CD8(+) T cells from 60 min after infusion, while HBPs increased CD4(+) T cell recruitment by 120 min. PSP-I/PSP-II but not HBPs induced PMN migration to the surface epithelium by 10 min. PMN numbers were elevated 5-fold by 30 min and 7-fold from 60 min. with PMNs detectable in the lumen from 30 min after infusion. Six-fold more PMNs were collected from the uterine lumen of PSP-I/PSP-II-infused sows compared to controls at 3 h after infusion. These data show that PSP-I/PSP-II heterodimer in seminal plasma has a predominant role in triggering the recruitment of uterine PMNs and T cells after mating, initiating a cascade of transient and long-lasting immunological events. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
|
|
| 16. |
- Svensson, Judit, et al.
(författare)
-
Gene expression and protein secretion patterns in decidual macrophages and different M1 and M2 macrophage populations with focus on M-CSF and IL-10 as polarising factors in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 151-151
- 2011
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 90:2, s. 151-151
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: We have recently observed (Svensson et al., data to be published) that M-CSF and IL-10, among several factors tested, are able to induce macrophages (MΦ) with phenotypic characteristics of decidual MΦ with expression of typical M2, or immune regulatory, cell surface markers (scavenger receptor, mannose receptor, DC-SIGN). The aim of this study was to investigate in a comprehensive manner whether this finding could be shown by an extended mapping of secreted molecules and also at the gene expression level.Materials and methods: CD14+ blood monocytes and decidual MΦ from healthy first trimester pregnant women (n = 11) were isolated by immunomagnetic cell sorting (MACS). MΦ were also generated in vitro from MACS-sorted CD14+ blood monocytes from non-pregnant women. RNA was isolated from blood monocytes and MΦ and the expression of 100 decidual MΦ-associated genes (Gustafsson et al., PlosOne 2008) was analysed with a custom microarray. RT-PCR was used to analyse the gene expression of IRF5, which was recently associated with classically activated (M1) MΦ. A multiplex bead assay was used to quantify the levels of cytokines and chemokines in conditioned media.Results: To estimate the similarity of the in vitro differentiated MΦ with decidual MΦ, we performed hierarchical clustering of differentially regulated genes. M1 MΦ and MΦ treated with GM-CSF and IL-4/13 formed their own branches, indicating transcriptional profiles clearly differing from all other MΦ types analysed. MΦ differentiated with M-CSF alone or with IL-10, regardless of the growth factor used, clustered together with decidual MΦ, supporting their close relationship. Genes similarly regulated in these macrophages were not restricted to immune modulating genes. This group included the M2-associated chemokines CCL2 and CCL18, the immune modulating B7 family-related VSIG4, the angiogenic insulin-like growth factor-1 and the M2-associated folate receptor β-encoding FOLR2 and selenoprotein-encoding SEPP1. The M2 polarisation status of decidual MΦ was confirmed by low expression of the M1-associated transcription factor IRF5, and comparable levels were detected in M-CSF- and IL-10-stimulated MΦ. IRF5 expression was higher in M1 MΦ and, surprisingly, also in IL-4/13-stimulated MΦ. As to protein secretion, decidual and M-CSF/IL-10-stimulated MΦ were found to produce comparable levels of IL-10 and the pro-inflammatory cytokines IL-6 and TNF, while M1 MΦ produced significantly higher levels of TNF and did not produce IL-10. Decidual and M-CSF/IL-10-stimulated MΦ also produced high levels of the monocyte- and granulocyte-recruiting chemokines CCL2, CCL4 and CXCL1, while the Th1 cell-recruiting CXCL10 and the Th2 cell-recruiting CCL22 were only produced at low levels. CXCL10 was highest in M1 MΦ, while CCL22 levels were highest in GM-CSF and/or IL-4/13-stimulated MΦ.Conclusions: Our data consistently shows a central role for M-CSF and IL-10 as polarising agents for decidual MΦ, while Th2 and pro-inflammatory agents induce MΦ with clearly differing characteristics. We hypothesise that decidual MΦ have a predominant homeostatic function. This is supported by their low production of both Th1 and Th2 cell-recruiting chemokines. It is thus likely that M-CSF and IL-10 shape the polarisation of decidual MΦ contributing to the homeostatic and tolerant immune environment required for successful fetal development.
|
|
| 17. |
|
|
