Rudi Steffensen

• PhD
• Laboratory Manager at Aalborg University Hospital

Objective: Patients are increasingly using and requesting LT4/LT3 combination treatment for persistent hypothyroid symptoms, but the efficacy and side effects of long-term therapy remain largely unexplored. This study aimed to describe the patient group experiencing a long-lasting impact of LT4/LT3 and evaluate their Quality of Life (QoL) and hypot...

Background In 2010, Denmark was the first country to implement a targeted routine antenatal anti‐D prophylaxis (tRAADP) program, offering fetal RHD genotyping to all nonimmunized D negative pregnant women. The program represented a shift from only postnatal prophylaxis to a combined antenatal and postnatal prophylaxis. This study aimed to evaluate...

Objective: The north-south gradient hypothesis proposes that individuals with rheumatoid arthritis (RA) residing in southern regions manifest a younger age of onset and milder disease compared to their northern counterparts. This study aimed to compare treatment-naïve, new-onset RA patients in Denmark and Turkey, examining demographic, clinical, l...

Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%–3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune‐related factors may play a role. P...

Genetic variation in the FCGR3B gene is responsible for different variants of human neu-trophil antigen 1 (HNA-1). Laboratory techniques currently utilized for routine HNA-1 genotyping, predominantly PCR-sequence-specific primer (PCR-SSP) and PCR-sequence-based typing (PCR-SBT), lack specificity for FCGR3B. This study compares the capabilities and...

Molecular HLA typing techniques are currently undergoing a rapid evolution. While real‐time PCR is established as the standard method in tissue typing laboratories regarding allocation of solid organs, next generation sequencing (NGS) for high‐resolution HLA typing is becoming indispensable but is not yet suitable for deceased donors. By contrast,...

Autoimmune neutropenia (AIN) in early childhood is characterized by chronic neutropenia and positivity for human neutrophil antibodies (HNA), resulting in the excessive destruction of neutrophils. The association between regulatory T cells (Tregs) and AIN has been described, and in this study, we investigated three Treg‐associated genes, IL‐2 , IL‐...

The clinical presentation of CD21 deficiency in 2 siblings caused by a novel mutation in the CD21 gene is reported, and the frequency of this mutation in the Danish population is explored. Successful treatment with IgG replacement in both patients with CD21 deficiency is also reported.

HLA studies in patients with autoimmune neutropenia (AIN) have shown very consistent results for the association with HLA class II alleles at low resolution. This study aimed to examine the association of both HLA class I and class II at high resolution to clarify the contribution of risk alleles to the disease. A total of 107 AIN patients were gen...

The poor remodeling of placental spiral arteries seen in preeclampsia is also discussed to contribute to recurrent pregnancy loss (RPL) preceded by abnormal angiogenesis and excessive complement activation. Low levels of Mannose-binding-lectin (MBL), a pattern recognition molecule (PRM) of the lectin pathway, have been found in women with RPL. We p...

Background The DNA-binding peptide LL37 is a suspected autoantigen in psoriasis. It can be found in neutrophil extracellular traps (NETs) which have been suggested to play a role in the pathogenesis of the disease. Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, can be implicated in the formation of NETs. We hypothesiz...

Immune system aberrations are suggested to be an important factor in the pathophysiology of unexplained secondary recurrent pregnancy loss (sRPL). The objective was to investigate if the sex ratio of the firstborn child in sRPL patients differs from the background population and whether the sex of the firstborn child has a negative impact on the pr...

The emerging pathogen Campylobacter concisus has been isolated from patients with gastrointestinal diseases; however, it is also present in the gut of healthy individuals. The aim of this study was to compare IL-8 production in HT-29 cells after infection with C. concisus from different gastrointestinal disease phenotypes. Additionally, to investig...

Autoimmune neutropenia (AIN) in early childhood is caused by autoantibodies directed against antigens on the neutrophil membrane and is a frequent cause of neutropenia in children. Association of AIN with Fcγ receptor (FCGR) 3B variants is well described. In this study, we investigate genetic variations in the FCGR locus and copy number variation o...

Introduction It is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this assoc...

Introduction Accumulating evidence support that mannan-binding lectin (MBL) is a promising prognostic biomarker for risk-stratification of diabetic micro- and macrovascular complications. Serum MBL levels are predominately genetically determined and depend on MBL genotype. However, Type 1 diabetes (T1D) is associated with higher MBL serum levels fo...

Introduction Recurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses in the first trimester, affects around 5% of fertile women. The underlying causes remain unknown in up to 60% of patients; however, most studies point at an immunological pathology in unexplained RPL, and therefore, an effective treatment may be immunom...

Background: Autoimmune neutropenia of early childhood (AIN) is caused by autoantibodies directed against antigens on the neutrophil membrane. The ABO, secretor, and Lewis histo-blood group systems control the expression of carbohydrate antigens and have previously been linked to autoimmune diseases. We aimed to investigate the association between...

STUDY QUESTION Are low or high plasma mannose binding lectin (p-MBL) levels associated with recurrent pregnancy loss (RPL) and the reproductive and perinatal outcomes before and after RPL? SUMMARY ANSWER The prevalence of low p-MBL levels was significantly higher in RPL patients while high levels were significantly less prevalent. No association w...

Objectives: The aim of the study was to create a simple assay for microchimerism detection independent of sex and without HLA genotyping. Methods: The method is based on detection of insertion or deletions utilizing a multiplex PCR followed by fragment analysis by capillary electrophoresis, and probe-based qPCR assays. A total of 192 samples, ta...

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in u...

Purpose The current study aimed to investigate in an Armenian population the levels of pattern recognition molecules (PRMs) of lectin complement pathway (LCP), MBL (mannan-binding lectin) and M-ficolin in plasma in ischemic stroke (IS), and the possible association of 11 single nucleotide polymorphisms (SNPs) in MBL2, FCN1 and FCN2 genes. Patients...

Transfusion‐Related Acute Lung Injury (TRALI) has been associated with neutrophil reacting antibodies in transfused blood products. We report a case of life‐threatening TRALI in an obstetric patient triggered by transfusion from a non‐transfused male blood donor. A residual risk of TRALI exist, even in a male‐only plasma setting. Transfusion‐Relate...

Many cases of recurrent pregnancy loss (RPL) defined as ≥3 consecutive pregnancy losses are suggested to be caused by an aberrant maternal immune response against the fetus or trophoblast. Human leukocyte antigen (HLA)–DRB1 and -DQB1 polymorphisms are associated with most autoimmune disorders and studies of HLA-DBB1 polymorphism in RPL patients are...

Background Autoimmune neutropenia of infancy (AIN) is a frequent cause of neutropenia in children. The disease is caused by antibodies against epitopes on the immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb). We investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)‐DR, and HLA‐DQ alleles with AI...

Aims In individuals at increased risk of infections, e.g., patients with type 2 diabetes, low MBL may have detrimental effects. We used the Mendelian randomization principle to examine whether genetically low MBL is a risk factor for developing infections in patients with type 2 diabetes. Methods Serum MBL (n=7305) and MBL genotype (n=3043) were d...

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with S...

Objective: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease (CVD) in diabetes, but the nature of the association is unclear. We investigated the association between MBL and the risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. Research design and methods: In a cohort study of 7,588 patients w...

Background Previous studies indicate that genetic susceptibility and phenotype of rheumatoid arthritis (RA) differ between the populations. Objectives To compare the clinical, serologic expression and the presence of shared epitopes (SE) of incident RA in two different populations, one from Northern and the other from Southern Europe. Methods Dat...

Background: Obstructive impairment of lung function is a complication following allogeneic hematopoietic stem cell transplantation (HSCT) and may progress to bronchiolitis obliterans that has a high mortality rate.

Objectives: Ficolin-3 deficiency is caused by a mutation (+1637delC) in the FCN3 gene. It is a rare condition and has been associated with both infection and autoimmune disease including Systemic Lupus Erythematosus (SLE). Here we investigated if ficolin-3 deficiency is more frequent in patients than in controls and attempted to identify a common p...

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Objectives The number of dinucleotide repeats (GT) nmodulate expression of heme oxygenase 1 (HMOX1), a stress response gene. Multiple repeats might affect chronic obstructive pulmonary disease (COPD) susceptibility. We aimed to investigate the association of this polymorphism with COPD and its interaction with occupational exposures (vapor, gas, du...

Unaccustomed eccentric exercise leads to impaired microvascular function but the underlying mechanism is unknown. In this study, we evaluated the role of oxidative stress and of nitric oxide (NO) bioavailability. Thirty young men and women performed eccentric contractions of the tibialis anterior (TA) muscle (ECC), with the contralateral leg servin...

Purpose Ficolin-3 deficiency is caused by a mutation (+1637delC) in the FCN3 gene. It is a rare condition and has been associated with both infection and autoimmune disease including systemic lupus erythematosus (SLE). Here we investigated if ficolin-3 deficiency is more frequent in patients than in controls and tried to identify a common phenotype...

Objective: The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that...

Alloantibodies against human neutrophil antigens (HNA) are involved in neonatal alloimmune neutropenia (NIN) and transfusion related acute lung injury (TRALI). The LABScreenMULTI assay (LSMUTR) (One Lambda, Inc.) is a novel neutrophil alloantibody detection assay based on the Luminex platform. Potential: Rapid anti-HNA-1a, -1b, -1c, -2, -3a, -3b, -...

Primary autoimmune neutropenia (AIN) of infancy is the most common form of neutropenia in young children. The median age at diagnosis is 8 months and the reported incidence is 1:100.000. The etiology of the disease is unknown, but primary AIN is caused by antibody mediated destruction of neutrophils. The auto-antibodies are frequently directed agai...

Antibody mediated Transfusion Related Acute Lung Injury (TRALI) is a transfusion reaction associated with high morbidity, and fatalities are reported in 10% of cases. TRALI is typically related to the presence of donor related anti-human leukocyte antigens (HLA) or anti-human neutrophil antigens (HNA) antibodies in the blood products. These antibod...

Antibody mediated Transfusion Related Acute Lung Injury (TRALI) is a transfusion reaction associated with high morbidity, and fatalities are reported in 10% of cases. TRALI is typically related to the presence of donor related anti-human leukocyte antigens (HLA) or anti-human neutrophil antigens (HNA) antibodies in the blood products. These antibod...

Introduction During pregnancy, the maternal immune system must cope with the semi-allogeneic fetus in order to facilitate a successful pregnancy. The extra-villous trophoblast cells situated at the feto-maternal interface express high amounts of the immune regulatory non-classical human leukocyte antigen-G (HLA-G). A 14 base pair insertion/deletion...

Objectives: In previous studies, around half of all hypothyroid patients preferred levo-thyroxine (L-T4) + levo-triiodothyronine (L-T3) combination therapy, 25% preferred T4, and 25% had no preference. The reason for this is yet to be explored. Methods: A total of 45 overtly autoimmune, hypothyroid patients - now euthyroid on ≥6 months' L-T4 the...

The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single-nucleotide polymorphisms (SNPs) involved in the immun...

Mounting evidence indicates that adverse activation of the complement system plays a role in the development of diabetic vascular complications. Plasma levels of the complement proteins mannan-binding lectin (MBL) and its associated serine proteases (MASP-1 and MASP-2) are elevated in diabetes. We hypothesised that single nucleotide polymorphisms (...

Birth weight and placental weight are crucial parameters for the survival of fetuses and newborns in mammals. High variation in the MHC is important for an effective adaptive immune response. The maternal immune system must be controlled in relation to the semi-allogenic fetus. The immunoregulatory HLA/MHC class Ib gene, HLA-G, is strongly expresse...

Problem: Women with secondary recurrent pregnancy loss (RPL) after a boy have a reduced chance of live birth in the first pregnancy after referral if they carry HY-restricting HLA class II alleles, but long-term chance of live birth is unknown. Methods of study: Live birth was compared for 540 women with unexplained secondary RPL according to fi...

The human major histocompatibility complex class II (MHCII) isotype HLA-DR is currently used as an activation marker for T cells. However, whether an endogenous protein expression or a molecular acquisition accounts for the presence of HLA-DR on T cells remains undetermined and still controversial. In order to further characterize this phenomenon,...

Background: Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbat...

Background and objectives: The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotropy. It has also been proposed that the survival of...

Objective: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (pSP-D) and SP-D gene (SFTPD) single nucleotide polymorphism...

Background Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. Methods We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin’s lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) a...

Background: Genetic polymorphisms in mannose-binding lectin (MBL2) gene may influence serum MBL2 protein level that may be linked to reduced lung function and exacerbation. The aim of this study was to evaluate whether MBL2 genotypes and serum levels predicts exacerbation in COPD. Methods: 277 COPD patients (mean 67.5 years, GOLD II-IV) were enroll...

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 prospect...

To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 (MBL2), collagen1α1 (COL1A1), factor II and factor V Leiden genes. In a case-control study, potential maternal biomarkers for cervical insufficiency were...

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune mediated survival and proliferation signals from the tumour microenvironment. Inherited genetic variation influences this complex interaction. Eighty-nine studies investigating immune-response genes in DLBCL and FL were critically reviewed. Relatively consisten...

Background M-ficolin is a pattern recognition molecule that collaborates with associated serine proteases as an activator of the complement system. High M-ficolin levels are strongly associated with high disease activity in early RA and low levels at baseline are strong predictors of both remission and low disease activity after one year (1). Singl...

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,...

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 bl...

Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on trophoblast cells and has been proposed to have immunomodulatory functions during pregnancy. Soluble HLA-G1 (sHLA-G1) can be generated by the shedding of membrane-bound HLA-G molecules; however, three soluble isoforms also exist (HLA-G5 to -G6)....

Introduction: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Scor...

Objective Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide pr...

Recurrent miscarriage (RM) is a multifactorial disorder with acknowledged genetic heritability that affects ∼3% of couples aiming at childbirth. As Copy Number Variants (CNVs) have been shown to contribute to reproductive disease susceptibility, we aimed to describe genome-wide profile of CNVs and identify common rearrangements modulating risk to R...

Background Single nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene are implicated in the regulation of the constitutional CRP expression and its response to pro-inflammatory stimuli. Previous reports suggest that these effects may influence instruments for clinical decision-making based on CRP, e.g. DAS28. Objectives To investig...

Background: Critically ill children are susceptible to nosocomial infections, which contribute to adverse outcomes. Deficiencies in the innate immunity lectin pathway of complement activation are implicated in a child's vulnerability to infections in conditions such as cancer, but the role during critical illness remains unclear. We hypothesized t...

MASP-1 is the first protein in the activation of the lectin pathway and MASP-1 is, like its isoforms MASP-3 and MAp44, encoded by the MASP1 gene. Our aim was to explore associations between polymorphisms in MASP1 and corresponding concentrations of MASP-1, MASP-3, and MAp44 in plasma as well as the genetic contribution to the equilibrium between th...

Figure S1. (TIF)

Problem: Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown. Method of study: Plasma was repeatedly sampled in the first trimester from 47 RM patients. The concentrations of five cytokines including tu...

Objective: To confirm the effect of single nucleotide polymorphisms (SNPs) in chorionic gonadotropin beta (CGB) genes in modulating the susceptibility to recurrent miscarriage (RM) in Danes and in a meta-analysis across Danes and the discovery samples from Estonia and Finland. Design: Case-control association study, restriction fragment length p...

The innate immune system encompasses various recognition molecules able to sense both exogenous and endogenous danger signals arising from pathogens or damaged host cells. One such pattern-recognition molecule is M-ficolin, which is capable of activating the complement system through the lectin pathway. The lectin pathway is multifaceted with activ...

Assay information for the 26 SNPs genotyped in 346 blood donors. Data on the forward and reverse primers regarding the not custom-designed assays are not available for commercial reasons. (DOCX)

Frequencies of non-synonymous and stop mutations in the FCN1 in 4300 unrelated European-American descendants from the Exome Variant Server, NHLBI GO Exome Sequencing Project (ESP), Seattle, WA. Data is sorted by the frequency of heterozygosity, with the most frequent at the top. The five non-synonymous SNPs found in 350 Danes are marked with red. (...

SNPs exploration sequencing in the FCN1 gene of 46 selected individuals. All SNPs were in Hardy-Weinberg equilibrium except rs2989721, which had an observed heterozygosity of 0.125, a predicted heterozygosity of 0.492 and a Hardy-Weinberg equilibrium p value <0.001. This was most likely due to only 54.5% were genotype for this SNP. SNPs in bold wer...