P–420 uncomplicated oocyte donation pregnancies display elevated CD163 positive type 2 macrophage load in the decidua, which is associated with fetal-maternal HLA class II mismatches

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
X Tian ◽  
K T S Aiyer ◽  
H M Kapsenberg ◽  
D L Roelen ◽  
M L V D Hoorn ◽  
...  

Abstract Study question Do quantity and composition of decidual macrophages differ between uncomplicated oocyte donation (OD) pregnancies and non-OD in vitro fertilization (IVF) pregnancies? Summary answer OD placentas show higher decidual CD163 positive fraction within the total macrophage population compared to non-OD IVF placentas. What is known already The embryo of an OD pregnancy is completely allogeneic to the mother, which may lead to a bigger challenge for the maternal immune system to tolerize the fetus compared to autologous pregnancies. Placental macrophages may be essential in maintaining a healthy pregnancy. Macrophages can be classified into different categories based on phenotype and characteristics, in which type 2 macrophages are thought to exhibit immune suppressive activity. Study design, size, duration This retrospective case-control study included patients who delivered in the Leiden University Medical Center between January 1st 2006 and July 1st 2016. A total of 42 pregnancies were enrolled in this study, conceived by uncomplicated singleton OD pregnancies (n = 25) or non-OD IVF pregnancies (n = 17). Medical records were reviewed and clinical data were collected. Placental tissue samples were collected for immunohistochemical staining and blood samples were collected for HLA typing. Participants/materials, setting, methods Placentas were collected and immunohistochemically stained for CD14 (pan-macrophage marker) and CD163 (type 2 macrophage marker). The extent of staining was quantitated by digital image analysis software. To assess mismatching, maternal and fetal DNA was typed for HLA-A, -B, C, -DRB1, and -DQB1. Main results and the role of chance A significantly lower percentage of CD14 positive staining was observed in the decidua basalis of OD pregnancies compared to non-OD IVF pregnancies (p = 0.030). Consequently, the CD163/CD14 ratio in OD group was higher than in non-OD IVF group (p = 0.243). In the parietalis, OD pregnancies demonstrated a significantly higher percentage of CD163+ staining (p = 0.040) and a significantly higher CD163/CD14 ratio (p = 0.032) compared to non-OD IVF group. The reproducibility of this quantitative analysis was found to be high. OD group was separated into a syngeneic group (number of mismatches lower than half of the antigens per HLA locus) and an allogeneic group (number of mismatches higher than half of the antigens per HLA locus). Significant differences of CD163+ and CD163/CD14 ratio were found in the decidua parietalis when comparing the HLA-classII-allogeneic OD group with the non-OD IVF group (p = 0.047). This difference was not found for the HLA-class-II-syngeneic OD group. Limitations, reasons for caution Our study only focused on decidua basalis and parietalis, no other locations in the placentas. Larger sample size might be needed to verify the association between macrophages and HLA mismatches. Wider implications of the findings: To our knowledge, this study is the first to quantify a higher CD163 positive M2 macrophages load within the total decidual macrophages of uncomplicated OD pregnancy compared to non-OD IVF pregnancies. Trial registration number Not applicable

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
X Tian ◽  
K T S Aiyer ◽  
H M Kapsenberg ◽  
D L Roelen ◽  
M L V D Hoorn ◽  
...  

Abstract Study question Do quantity and composition of decidual macrophages differ between uncomplicated oocyte donation (OD) pregnancies and non-OD in vitro fertilization (IVF) pregnancies? Summary answer OD placentas show higher decidual CD163 positive fraction within the total macrophage population compared to non-OD IVF placentas. What is known already The embryo of an OD pregnancy is completely allogeneic to the mother, which may lead to a bigger challenge for the maternal immune system to tolerize the fetus compared to autologous pregnancies. Placental macrophages may be essential in maintaining a healthy pregnancy. Macrophages can be classified into different categories based on phenotype and characteristics, in which type 2 macrophages are thought to exhibit immune suppressive activity. Study design, size, duration This retrospective case-control study included patients who delivered in the Leiden University Medical Center between January 1st 2006 and July 1st 2016. A total of 42 pregnancies were enrolled in this study, conceived by uncomplicated singleton OD pregnancies (n = 25) or non-OD IVF pregnancies (n = 17). Medical records were reviewed and clinical data were collected. Placental tissue samples were collected for immunohistochemical staining and blood samples were collected for HLA typing. Participants/materials, setting, methods Placentas were collected and immunohistochemically stained for CD14 (pan-macrophage marker) and CD163 (type 2 macrophage marker). The extent of staining was quantitated by digital image analysis software. To assess mismatching, maternal and fetal DNA was typed for HLA-A, -B, C, -DRB1, and -DQB1. Main results and the role of chance A significantly lower percentage of CD14 positive staining was observed in the decidua basalis of OD pregnancies compared to non-OD IVF pregnancies (p = 0.030). Consequently, the CD163/CD14 ratio in OD group was higher than in non-OD IVF group (p = 0.243). In the parietalis, OD pregnancies demonstrated a significantly higher percentage of CD163+ staining (p = 0.040) and a significantly higher CD163/CD14 ratio (p = 0.032) compared to non-OD IVF group. The reproducibility of this quantitative analysis was found to be high. OD group was separated into a syngeneic group (number of mismatches lower than half of the antigens per HLA locus) and an allogeneic group (number of mismatches higher than half of the antigens per HLA locus). Significant differences of CD163+ and CD163/CD14 ratio were found in the decidua parietalis when comparing the HLA-classII-allogeneic OD group with the non-OD IVF group (p = 0.047). This difference was not found for the HLA-class-II-syngeneic OD group. Limitations, reasons for caution Our study only focused on decidua basalis and parietalis, no other locations in the placentas. Larger sample size might be needed to verify the association between macrophages and HLA mismatches. Wider implications of the findings To our knowledge, this study is the first to quantify a higher CD163 positive M2 macrophages load within the total decidual macrophages of uncomplicated OD pregnancy compared to non-OD IVF pregnancies. Trial registration number not applicable


2005 ◽  
Vol 12 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Ayesha A. Motala ◽  
Marc Busson ◽  
Einas M. Al-Harbi ◽  
Manal A. A. Khuzam ◽  
Emtiaz M. D. Al-Omari ◽  
...  

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.


2020 ◽  
Vol 105 (3) ◽  
pp. e245-e254 ◽  
Author(s):  
Thomas Jacobi ◽  
Lucas Massier ◽  
Nora Klöting ◽  
Katrin Horn ◽  
Alexander Schuch ◽  
...  

Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.


2006 ◽  
Vol 13 (11) ◽  
pp. 1296-1298 ◽  
Author(s):  
Wassim Y. Almawi ◽  
Saria F. Wakim-Ghorayeb ◽  
Mona R. Arekat ◽  
Pierre Najm ◽  
Sose H. Keleshian ◽  
...  

ABSTRACT The association of HLA class II with type 2 diabetes (T2DM) was investigated in Bahraini and Lebanese subjects. DRB1*070101 (Lebanese and Bahraini) and DQB1*0201 (Lebanese) were susceptibility-conferring alleles, and unique susceptibility-conferring/protective haplotypes were found in both patient groups. Regression analysis confirmed that DRB1*070101-DQB1*0201 (Bahraini) and DRB1*110101-DQB1*0201 (Lebanese) were susceptibility-conferring haplotypes.


2000 ◽  
Vol 61 (10) ◽  
pp. 1031-1038 ◽  
Author(s):  
Elva Pérez-Luque ◽  
Juan Manuel Malacara ◽  
Angélica Olivo-Dı́az ◽  
Carmen Aláez ◽  
Héctor Debaz ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8503-8503
Author(s):  
Y. S. Chun ◽  
Y. Wang ◽  
J. E. Gershenwald ◽  
M. I. Ross ◽  
M. M. Johnson ◽  
...  

8503 Background: Prior reports have suggested a link between specific HLA class II alleles, including HLA-DRB1*1101, and melanoma recurrence. We therefore investigated the relationship between HLA class II alleles and clinical outcome in a large population of patients who presented with localized melanoma. Methods: HLA class II alleles were determined by typing of genomic DNA from patients who presented with localized melanoma (AJCC stage IA-IIC). Patients found to have occult regional disease by sentinel node biopsy were excluded. Log-rank and Cox analysis of outcome versus standard prognostic factors and common HLA class II alleles (=5% of the population) was performed. Results: 1,241 patients underwent HLA typing. The median primary tumor thickness was 1.1 mm, 16% were ulcerated, and the median follow-up was 56 months. Tumor thickness, ulceration, and Clark level were independent predictors of recurrence. The HLA class II allele HLA-DRB1*1101 (11% of the population) independently predicted a higher risk of recurrence [hazard ratio (HR) 2.04, P=0.004] while HLA-DRB1*0401 (20% of the population) predicted a lower risk of recurrence (HR 0.42, P=0.004). HLA- DRB1*1101 was a particularly strong predictor of recurrence in stage I patients (HR 2.73, P<0.0001). Among patients who recurred, HLA- DRB1*1101 was an independent predictor of local-regional vs. distant recurrence (HR 2.7, P=0.007), and was more common in those whose first recurrence was isolated to the regional nodal basin, compared to those whose first recurrence was elsewhere or in multiple locations (24% HLA-DRB1*1101-positive vs. 14%, P<0.009). Conclusions: These results confirm that HLA-DRB1*1101 is a genetic marker of increased risk of melanoma recurrence, while HLA-DRB1*0401 is a marker of decreased risk of recurrence. HLA-DRB1*1101 is a particularly strong marker among the group of patients predicted clinically to be at the lowest overall risk for recurrence, and independently predicts pattern of recurrence (regional nodal failure). This information is of value in the development of surveillance strategies for melanoma patients, as well as the selection, stratification and randomization of early-stage melanoma patients for clinical trials. No significant financial relationships to disclose.


2020 ◽  
Vol 137 ◽  
pp. 103074 ◽  
Author(s):  
K. van Bentem ◽  
M. Bos ◽  
C. van der Keur ◽  
S.H. Brand-Schaaf ◽  
G.W. Haasnoot ◽  
...  

2018 ◽  
Vol 128 ◽  
pp. 60
Author(s):  
K. van Bentem ◽  
M. Bos ◽  
C. van der Keur ◽  
M. Eikmans ◽  
S. Heidt ◽  
...  

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