Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expres... more Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.
The aim of this study was to point out the possible ethnic differences of HLA class I genotypes b... more The aim of this study was to point out the possible ethnic differences of HLA class I genotypes between a group of 43 healthy unrelated Unuits, born in Greenland with residence in Denmark and a group of 30 healthy unrelated Danes. We studied the genotype frequencies of HLA-...
In Denmark approximately 3,600 patients are diagnosed with colorectal cancer (CRC) every year. 75... more In Denmark approximately 3,600 patients are diagnosed with colorectal cancer (CRC) every year. 75-80% of patients may undergo intended curative resection, but the disease recurs in about 40% within five years and the prognosis is poor. Hence, there is a need for biological markers that could be used for detection, evaluation of prognosis, therapy selection and monitoring. The serum proteins of the innate immune system mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are novel biomarkers under validation in CRC. Low preoperative MBL levels are predictive of pneumonia which subsequently is associated with poor survival. High MASP-2 levels predict recurrence and poor survival.
Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associat... more Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this. We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174 normoalbuminuric patients (103 men, age 43 [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median. Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002). High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.
Neutrophil antigens are implicated in a variety of clinical conditions, including neonatal immune... more Neutrophil antigens are implicated in a variety of clinical conditions, including neonatal immune neutropenia, transfusion-related acute lung injury, refractoriness to granulocyte transfusions, febrile transfusion reactions, and autoimmune neutropenia. In this report, we describe simultaneous genotyping of human neutrophil antigens (HNA)-1, -3, -4, and -5 using PCR with allele-specific TaqMan probes and end-point fluorescence detection, which is a robust, rapid, and reproducible method, allowing for high-throughput genotyping.
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune-mediated... more Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune-mediated survival and proliferation signals from the tumor microenvironment. Inherited genetic variation influences this complex interaction. A total of 89 studies investigating immune-response genes in DLBCL and FL were critically reviewed. Relatively consistent association exists for variation in the tumor necrosis factor alpha (TNFA) and interleukin-10 loci and DLBCL risk; for DLBCL outcome association with the TNFA locus exists. Variations at chromosome 6p31-32 were associated with FL risk. Importantly, individual risk alleles have been shown to interact with each other. We suggest that the pathogenetic impact of polymorphic genes should include gene-gene interaction analysis and should be validated in preclinical model systems of normal B lymphopoiesis and B-cell malignancies. In the future, large cohort studies of interactions and genome-wide association studies are needed to extend the present findings and explore new risk alleles to be studied in preclinical models.
European journal of obstetrics, gynecology, and reproductive biology, 2014
To investigate a possible association between endometriosis and low levels of mannan-binding lect... more To investigate a possible association between endometriosis and low levels of mannan-binding lectin (MBL). Case-control study of blood samples from 100 patients with endometriosis compared with results from a group of 350 blood donors. The frequency of MBL levels <100ng/ml was 14.0% in patients and 14.9% in controls. Correspondingly, the frequencies of low producing MBL genotypes were 15.0% and 16.0%, respectively. No association was found between endometriosis and low levels of MBL.
Postoperative infection is a major cause of morbidity and mortality. We investigated two serum ma... more Postoperative infection is a major cause of morbidity and mortality. We investigated two serum markers for their ability to identify patients at risk for postoperative infection. Mannan-binding lectin (MBL) is a central molecule of the innate immune system and MBL deficiency is known to predispose to infection. Procalcitonin (PCT) is a sensitive marker for bacterial infection. We investigated 162 patients undergoing elective surgery for cancer of the gastrointestinal tract. Patients were classified as having no complications (group A), having infection for unknown reason (group B) or having sepsis after events like aspiration or anastomotic leakage (group C). Analysis was done pre- and postoperatively for serum levels of MBL, PCT and C-reactive-protein. DNA was preoperatively sampled and stored and later analysed for genetic polymorphisms of MBL. The preoperative serum levels of MBL were significantly lower in group B patients than in group A patients (1332 +/- 466 ng/ml versus 2523...
Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expres... more Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-untranslated region (3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.
Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expres... more Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-untranslated region (3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.
The aim of this study was to point out the possible ethnic differences of HLA class I genotypes b... more The aim of this study was to point out the possible ethnic differences of HLA class I genotypes between a group of 43 healthy unrelated Unuits, born in Greenland with residence in Denmark and a group of 30 healthy unrelated Danes. We studied the genotype frequencies of HLA-...
In Denmark approximately 3,600 patients are diagnosed with colorectal cancer (CRC) every year. 75... more In Denmark approximately 3,600 patients are diagnosed with colorectal cancer (CRC) every year. 75-80% of patients may undergo intended curative resection, but the disease recurs in about 40% within five years and the prognosis is poor. Hence, there is a need for biological markers that could be used for detection, evaluation of prognosis, therapy selection and monitoring. The serum proteins of the innate immune system mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are novel biomarkers under validation in CRC. Low preoperative MBL levels are predictive of pneumonia which subsequently is associated with poor survival. High MASP-2 levels predict recurrence and poor survival.
Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associat... more Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this. We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174 normoalbuminuric patients (103 men, age 43 [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median. Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002). High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.
Neutrophil antigens are implicated in a variety of clinical conditions, including neonatal immune... more Neutrophil antigens are implicated in a variety of clinical conditions, including neonatal immune neutropenia, transfusion-related acute lung injury, refractoriness to granulocyte transfusions, febrile transfusion reactions, and autoimmune neutropenia. In this report, we describe simultaneous genotyping of human neutrophil antigens (HNA)-1, -3, -4, and -5 using PCR with allele-specific TaqMan probes and end-point fluorescence detection, which is a robust, rapid, and reproducible method, allowing for high-throughput genotyping.
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune-mediated... more Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune-mediated survival and proliferation signals from the tumor microenvironment. Inherited genetic variation influences this complex interaction. A total of 89 studies investigating immune-response genes in DLBCL and FL were critically reviewed. Relatively consistent association exists for variation in the tumor necrosis factor alpha (TNFA) and interleukin-10 loci and DLBCL risk; for DLBCL outcome association with the TNFA locus exists. Variations at chromosome 6p31-32 were associated with FL risk. Importantly, individual risk alleles have been shown to interact with each other. We suggest that the pathogenetic impact of polymorphic genes should include gene-gene interaction analysis and should be validated in preclinical model systems of normal B lymphopoiesis and B-cell malignancies. In the future, large cohort studies of interactions and genome-wide association studies are needed to extend the present findings and explore new risk alleles to be studied in preclinical models.
European journal of obstetrics, gynecology, and reproductive biology, 2014
To investigate a possible association between endometriosis and low levels of mannan-binding lect... more To investigate a possible association between endometriosis and low levels of mannan-binding lectin (MBL). Case-control study of blood samples from 100 patients with endometriosis compared with results from a group of 350 blood donors. The frequency of MBL levels <100ng/ml was 14.0% in patients and 14.9% in controls. Correspondingly, the frequencies of low producing MBL genotypes were 15.0% and 16.0%, respectively. No association was found between endometriosis and low levels of MBL.
Postoperative infection is a major cause of morbidity and mortality. We investigated two serum ma... more Postoperative infection is a major cause of morbidity and mortality. We investigated two serum markers for their ability to identify patients at risk for postoperative infection. Mannan-binding lectin (MBL) is a central molecule of the innate immune system and MBL deficiency is known to predispose to infection. Procalcitonin (PCT) is a sensitive marker for bacterial infection. We investigated 162 patients undergoing elective surgery for cancer of the gastrointestinal tract. Patients were classified as having no complications (group A), having infection for unknown reason (group B) or having sepsis after events like aspiration or anastomotic leakage (group C). Analysis was done pre- and postoperatively for serum levels of MBL, PCT and C-reactive-protein. DNA was preoperatively sampled and stored and later analysed for genetic polymorphisms of MBL. The preoperative serum levels of MBL were significantly lower in group B patients than in group A patients (1332 +/- 466 ng/ml versus 2523...
Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expres... more Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-untranslated region (3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.
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Papers by Rudi Steffensen