American Journal of Reproductive Immunology, Mar 11, 2010
Cell communication comprises cell-cell contact, soluble mediators and intercellular nanotubes. Th... more Cell communication comprises cell-cell contact, soluble mediators and intercellular nanotubes. There is, however, another cell-cell communication by released membrane-bound microvesicles that convey cell-cell contact 'by proxy' transporting signals/packages of information from donor to recipient cells locally and/or at a distance. The nanosized exosomes comprise a specialized type of microvesicles generated within multivesicular bodies (MVB) and released upon MVB fusion with the plasma membrane. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells. Recently, it was discovered that the syncytiotrophoblast constitutively and throughout the pregnancy secretes exosomes. The placenta-derived exosomes are immunosuppressive and carry proteins and RNA molecules that in a redundant way influence a number of mechanisms and promote the fetal allograft survival. In this review, we summarize the current knowledge on the nature of placenta-derived exosomes and discuss their role in pregnancy.
... Nilsson, Kenneth. Nagaeva, Olga (Umeå University, Faculty of Medicine, Department of Clinical... more ... Nilsson, Kenneth. Nagaeva, Olga (Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology). Rantapää-Dahlqvist ... type: Manuscript (Other (popular science, discussion, etc.)). Language: English. URI: urn:nbn:se:umu:diva-3374. Permanent link ...
Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate d... more Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. A population-based follow-up cohort study. Participants visited the primary health care centre in Lycksele, Sweden in 1988-92. A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow-up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main outcome measurements. A clinically diagnosed diabetes at follow-up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies. At follow-up, 42/2278 (1.8%, 95% CI 1.2-2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow-up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3-18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8-12.6) in the fourth quartile of 2-h plasma glucose (>7.5 mmol L(-1)) and 7.2 (95% CI 4.8-11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L(-1)). Islet cell autoantibodies did not predict diabetes at follow-up. BMI measured at base line was as effective as 2-h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.
Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of di... more Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of diabetes in adults. We assessed the concordance in GAD65 autoantibody levels within subjects between three different GAD65Ab radio binding assays (RBA). Plasma samples from 112 diabetes patients (median age 50 years) initially classified with type 2 diabetes was randomly selected from a local diabetes registry. Coded samples were analyzed with two RBA employing (35)S-labeled GAD65. The first used the pEx9 plasmid (pEx9 RBA), the second employed the pThGAD65 plasmid (pThGAD65 RBA) to label GAD65 by in vitro transcription translation. We also used a commercial kit employing plasmid pGAD17 labelled with (125)I (pGAD17 RBA). Subsequent analyses followed standard procedures. Two different cut-offs for GAD65Ab positivity were used in all three assays. We calculated the correlation, concordance, and agreement between the assays. The proportion of GAD65Ab positivity differed between assays when low cut-offs were used (pEx9 RBA 25%, pThGAD65 RBA 17.9%, and pGAD17 RBA 12.5%, respectively). When high cut-offs were applied, the concordance between the pEx9 RBA and the pThGAD65 RBA was 97.3 while their concordance to the pGAD17 RBA was lower (88.4 and 87.4, respectively). There was a low agreement between both pEx9 RBA and pGAD17 RBA (0.45, 95% CI 0.20-0.70) and between pThGAD65 RBA and pGAD17 RBA (0.43, 95% CI 0.18-0.68). We found discrepancies in determining the GAD65Ab positivity, which constitutes a problem when GAD65Ab are used clinically. Further methodological GAD65Ab assays studies are warranted.
Expert Review of Obstetrics & Gynecology, Sep 1, 2010
ABSTRACT Exosomes are nanosized membrane-bound microvesicles that originate from the endosomal co... more ABSTRACT Exosomes are nanosized membrane-bound microvesicles that originate from the endosomal compartment and convey cell-cell contact `by proxy', transporting signals/packages of information between donor and recipient cells locally and/or at a distance. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram the recipient cells. Recently, it was discovered that the syncytiotrophoblast of human placenta continuously and constitutively secretes exosomes throughout pregnancy. These exosomes, delivered directly in the maternal blood surrounding the chorionic villi of the placenta, are immunosuppressive and pluripotent carrying proteins, mRNA and miRNA that can influence a number of biologic mechanisms and promote the fetal allograft survival. The current knowledge regarding placental exosomes and their role in pregnancy is summarized and discussed in this article.
American Journal of Reproductive Immunology, Mar 11, 2010
Cell communication comprises cell-cell contact, soluble mediators and intercellular nanotubes. Th... more Cell communication comprises cell-cell contact, soluble mediators and intercellular nanotubes. There is, however, another cell-cell communication by released membrane-bound microvesicles that convey cell-cell contact 'by proxy' transporting signals/packages of information from donor to recipient cells locally and/or at a distance. The nanosized exosomes comprise a specialized type of microvesicles generated within multivesicular bodies (MVB) and released upon MVB fusion with the plasma membrane. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells. Recently, it was discovered that the syncytiotrophoblast constitutively and throughout the pregnancy secretes exosomes. The placenta-derived exosomes are immunosuppressive and carry proteins and RNA molecules that in a redundant way influence a number of mechanisms and promote the fetal allograft survival. In this review, we summarize the current knowledge on the nature of placenta-derived exosomes and discuss their role in pregnancy.
... Nilsson, Kenneth. Nagaeva, Olga (Umeå University, Faculty of Medicine, Department of Clinical... more ... Nilsson, Kenneth. Nagaeva, Olga (Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology). Rantapää-Dahlqvist ... type: Manuscript (Other (popular science, discussion, etc.)). Language: English. URI: urn:nbn:se:umu:diva-3374. Permanent link ...
Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate d... more Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. A population-based follow-up cohort study. Participants visited the primary health care centre in Lycksele, Sweden in 1988-92. A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow-up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main outcome measurements. A clinically diagnosed diabetes at follow-up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies. At follow-up, 42/2278 (1.8%, 95% CI 1.2-2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow-up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3-18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8-12.6) in the fourth quartile of 2-h plasma glucose (>7.5 mmol L(-1)) and 7.2 (95% CI 4.8-11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L(-1)). Islet cell autoantibodies did not predict diabetes at follow-up. BMI measured at base line was as effective as 2-h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.
Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of di... more Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of diabetes in adults. We assessed the concordance in GAD65 autoantibody levels within subjects between three different GAD65Ab radio binding assays (RBA). Plasma samples from 112 diabetes patients (median age 50 years) initially classified with type 2 diabetes was randomly selected from a local diabetes registry. Coded samples were analyzed with two RBA employing (35)S-labeled GAD65. The first used the pEx9 plasmid (pEx9 RBA), the second employed the pThGAD65 plasmid (pThGAD65 RBA) to label GAD65 by in vitro transcription translation. We also used a commercial kit employing plasmid pGAD17 labelled with (125)I (pGAD17 RBA). Subsequent analyses followed standard procedures. Two different cut-offs for GAD65Ab positivity were used in all three assays. We calculated the correlation, concordance, and agreement between the assays. The proportion of GAD65Ab positivity differed between assays when low cut-offs were used (pEx9 RBA 25%, pThGAD65 RBA 17.9%, and pGAD17 RBA 12.5%, respectively). When high cut-offs were applied, the concordance between the pEx9 RBA and the pThGAD65 RBA was 97.3 while their concordance to the pGAD17 RBA was lower (88.4 and 87.4, respectively). There was a low agreement between both pEx9 RBA and pGAD17 RBA (0.45, 95% CI 0.20-0.70) and between pThGAD65 RBA and pGAD17 RBA (0.43, 95% CI 0.18-0.68). We found discrepancies in determining the GAD65Ab positivity, which constitutes a problem when GAD65Ab are used clinically. Further methodological GAD65Ab assays studies are warranted.
Expert Review of Obstetrics & Gynecology, Sep 1, 2010
ABSTRACT Exosomes are nanosized membrane-bound microvesicles that originate from the endosomal co... more ABSTRACT Exosomes are nanosized membrane-bound microvesicles that originate from the endosomal compartment and convey cell-cell contact `by proxy', transporting signals/packages of information between donor and recipient cells locally and/or at a distance. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram the recipient cells. Recently, it was discovered that the syncytiotrophoblast of human placenta continuously and constitutively secretes exosomes throughout pregnancy. These exosomes, delivered directly in the maternal blood surrounding the chorionic villi of the placenta, are immunosuppressive and pluripotent carrying proteins, mRNA and miRNA that can influence a number of biologic mechanisms and promote the fetal allograft survival. The current knowledge regarding placental exosomes and their role in pregnancy is summarized and discussed in this article.
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Papers by Lucia Mincheva-nilsson