PubMed Health⌕ Search

Biomedical subjects

O B Christiansen

Publications and source records attributed to O B Christiansen.

At least 19 recordsLinked to original sources
PubMed2004

Impact of the sex of first child on the prognosis in secondary recurrent miscarriage.

BACKGROUND: The carriage of a male fetus often initiates maternal immunological reactions against male-specific minor histocompatibility (HY) antigens, which, in theory, could result in subsequent recurrent miscarriage (RM). METHODS: Information about subsequent pregnancy outcome was procured among 182 women with RM after a birth (secondary RM) referred since 1986 using questionnaires, telephone interviews and registers. RESULTS: Significantly more of the women had had a male first-born as compared with a female first-born (110 versus 72; P < 0.02). By January 2002, 58% of those who had a male first-born had given birth to a second live infant compared with 76% of those who previously had had a female first-born (P = 0.01). Women in the former group had a significantly lower chance of having a second child than those in the latter (adjusted hazard ratio 0.59; 95% confidence interval 0.41-0.86). The number of miscarriages after admission and the risk of secondary infertility were significantly greater in women with a male first-born than among those with a female first-born (P < 0.001 and P = 0.02; respectively). CONCLUSIONS: A male first-born seems to be associated with a less favourable reproductive potential among women with secondary RM. Maternal immunization against HY antigens may be responsible for these findings.

Abortion, Habitual↗
PubMed2004

A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1*03 is associated with recurrent miscarriage.

BACKGROUND: Previous studies have demonstrated an association between recurrent miscarriage (RM) and the maternal HLA-DRB1*01 and -DRB1*03 alleles. The primary aim of the present study was to confirm or reject the hypothesis about this association in a larger case-control study. METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was carried out by the PCR-sequence-specific primer (SSP) method in 354 patients with unexplained RM and 202 fertile controls. These results were combined with the results from a previous study of 234 RM patients and 360 controls. RESULTS: The prevalence of patients with HLA-DRB1*03 was significantly increased compared with controls [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.1-1.9, P = 0.01, P corrected for the number of comparisons (Pc) = 0.02]. In patients with at least four previous miscarriages or with secondary RM, the association became even stronger (OR = 1.8, 95% CI = 1.3-2.5, P = 0.0005, Pc = 0.004; and OR = 1.8, 95% CI = 1.3-2.5, P = 0.0007, Pc = 0.006, respectively). There was no significant difference between patients and controls with regard to HLA-DRB1*01. CONCLUSION: The HLA-DRB1*03 allele or genes in linkage disequilibrium with it confer susceptibility to RM.

Abortion, Habitual↗
PubMed2004

Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome.

To determine if a 14-bp deletion/insertion polymorphism in the 3'-untranslated region of exon 8 of the gene encoding human leukocyte antigen (HLA)-G in a homozygous form is associated with repeated, unsuccessful in vitro fertilization (IVF) treatments, and with increased risk of recurrent spontaneous abortions (RSA), 29 white women undergoing IVF treatments, 61 RSA women and 93 fertile controls were HLA-G genotype. The HLA-G genotype, homozygous for the presence of the 14 bp sequence in exon 8, was significantly associated with reduced fertility with respect to unsuccessful IVF treatments and increased risk of recurrent miscarriage (combined P < 0.01). The 14-bp insertion/deletion polymorphism is associated with differences in HLA-G mRNA alternative splicing and levels of HLA-G. This might affect a possible immunomodulatory role of HLA-G expression in both the mother and foetus during implantation and pregnancy.

Abortion, Habitual↗
PubMed2003

Prospective, serial investigations of in-vitro lymphocyte cytokine production, CD62L expression and proliferative response to microbial antigens in women with recurrent miscarriage.

BACKGROUND: Lymphocytes from pregnant women with unexplained recurrent miscarriage (RM) may be characterized by a T-helper type 1-dominated cytokine production and a higher proliferative response to microbial recall antigens compared with normal pregnant women. METHODS: Serial blood samples were taken from 14 women with RM (at least three previous consecutive miscarriages) during the first 14 weeks of pregnancy, and one blood sample was taken from 15 control women in gestational weeks 7-8. Of the 14 pregnant RM patients, four produced a live birth and 10 miscarried. Lymphocytes were in-vitro-stimulated by mitogens, allogeneic cells and microbial antigens, and the production of a series of cytokines, the proliferative responses and lymphocytic expression of CD62L (which may be a marker of T-helper type 2 lymphocytes) were measured. RESULTS: Repeated measurements of cytokine production were reproducible during the first trimester. The proliferative responses to herpes simplex and tetanus antigens were increased, and the ratio of CD62L-/CD62L+ expressing CD4+CD45RO+ lymphocytes was decreased in patients compared with controls (P = 0.01, P < 0.01 and P < 0.01 respectively). CONCLUSION: The results of the in-vitro assays used were reproducible in serial testing during pregnancy. The importance of CD62L expression on lymphocytes for RM and the relevance of the maternal response to microbial antigens during pregnancy should be further explored.

Abortion, Habitual↗
PubMed2002

HLA-G polymorphisms in couples with recurrent spontaneous abortions.

The etiology of a fraction of recurrent spontaneous abortions (RSA) may involve immunological mechanisms. Aberrant profiles of Th1 and Th2 cytokines have been observed which are not present in uncomplicated pregnancies. Studies of classical HLA class I and II antigens in relation to RSA have not been conclusive. Furthermore, these antigens are not expressed in the placenta with the exception of HLA-C. However, HLA-G is expressed on especially invasive cytotrophoblasts and exists in both membrane and soluble forms. HLA-G may be involved in materno-fetal tolerance. Therefore, 61 RSA couples (with three or more spontaneous abortions) and 47 fertile control couples were HLA-G genotyped by direct DNA sequencing and analyzed for specific polymorphisms. No statistically significant differences were observed in the distribution of HLA-G alleles between controls and RSA couples, however, 15% of the RSA women carried the HLA-G*0106 allele compared to 2% of the control women. The 14 bp deletion polymorphism in exon 8 was investigated separately. There were a greater number of heterozygotes for the 14 bp polymorphism in the group of fertile control women than expected, according to Hardy-Weinberg equilibrium. Furthermore, the HLA-G alleles without the 14 bp sequence were prominent in the RSA males in contrast to the RSA women in whom alleles including the 14 bp sequence were frequently observed, especially as homozygotes. These results are discussed in relation to two hypotheses concerning HLA-G and RSA. A hypothesis of HLA-G histo-incompatibility between fetus/placenta and the mother was not supported by the data. Another hypothesis concerned certain HLA-G alleles associated with an altered expression profile of HLA-G isoforms or reduced expression of certain HLA-G isoforms.

Abortion, Habitual↗
PubMed1999

Mannan-binding lectin deficiency is associated with unexplained recurrent miscarriage.

Mannan-binding lectin (MBL) is a plasma protein which, upon binding to microbial carbohydrate structures, elicits activation of the complement system. The level of MBL is genetically determined. It has been reported that the frequency of low plasma levels of MBL is increased in patients with unexplained recurrent miscarriages (RM). In the present study plasma MBL levels were determined in 146 Danish women with RM and 41 of their husbands together with 49 Scottish RM women and 41 of their husbands. In both countries MBL levels were also investigated in a total of 444 controls. Based on the control data, a cut-off MBL level < 50 ng/ml was selected to define MBL deficiency. The typical odds ratio for MBL deficiency among female patients in the two populations was 1.68 (95% confidence limits 1.01-2.80, P<0.05) whereas it was 1.57 (95% confidence limits 0.72-3.42, not significant) for the male partners of the patients. There was a significant correlation between the frequency of MBL deficiency in RM women and the number of previous miscarriages (P < 0.01), whereas no such correlation was found in the husbands. The results indicate that maternal MBL deficiency is associated with RM. Maternal MBL deficiency might impair the immune defence against microorganisms at the feto-maternal interface.

Abortion, Habitual↗
PubMed1999

The possible role of classical human leukocyte antigens in recurrent miscarriage.

PROBLEM: If immunological factors play a role in the pathogenesis of recurrent miscarriage (RM), it is likely that associations between alleles of classical human leukocyte antigen (HLA) genes and RM exist. Our aim was to investigate HLA-C alleles in RM couples and HLA-DR and -DQ polymorphism in women with unexplained RM. METHOD OF STUDY: HLA-C alleles were investigated in 35 RM and 30 control couples and HLA-DR and -DQ allogenotypes were investigated in 234 RM patients and 360 controls. All HLA investigations were undertaken by DNA based methods. RESULTS: We found no difference between the RM and control couples in the degree of paternal incompatibility for maternal HLA-C alleles and the distribution of the two HLA-C supertypic specificities that are recognized differently by p58 killer cell inhibitory receptor (KIR) positive natural killer (NK) cells was similar in the two groups. In 97 women with at least four previous miscarriages, significantly higher frequencies of the HLA-DR1,DQ5 and -DR3,DQ2 haplotypes were found compared with 360 controls (P < 0.05 after correction for multiple comparisons). Among 94 RM patients followed prospectively, those with HLA-DR1 and/or -DR3 had a 62% miscarriage rate compared with only 29% among those without these alleles (P < 0.05). A large family study indicated that HLA-DR1 and/or -DR3 positive sisters and brothers' wives of probands with RM had an odds ratio of 5.0 for miscarrying their pregnancies compared with corresponding HLA-DR1 and -DR3 negative relatives. Finally, a meta-analysis of relevant studies based on a MEDLINE search showed that HLA-DR1, -DR3, and -DR4 were significantly increased in Caucasian women with RM. CONCLUSIONS: HLA-DR1, -DR3, and maybe -DR4 show association to RM in Caucasian women whereas no association to classical HLA class I genes including HLA-C can be detected in RM couples. The mechanism by which class II alleles confer susceptibility to RM might be by predisposing to hypersecretion of certain cytokines, e.g., tumor necrosis factor (TNF)-alpha at the feto-maternal interface.

Abortion, Habitual↗
PubMed1998

Histocompatibility antigen studies in women with recurrent miscarriages and Müllerian uterine anomalies.

OBJECTIVE: To determine whether the HLA alleles DR1, DR3, DR4 and DR10 which have been suggested to be risk markers for unexplained recurrent miscarriages also play a part in women with recurrent miscarriages with Müllerian uterine fusion anomalies. STUDY DESIGN: HLA-DR typing was undertaken in 28 women with recurrent miscarriage who had been surgically treated for Müllerian anomalies and in 360 controls. In the study group, outcome of pregnancies after surgery was correlated to the results of the HLA typing. RESULTS: In the study group, 61% were positive for HLA-DR1, -DR3, -DR4 or -DR10 compared with 65% of the controls (not significantly different). Among patients positive for these HLA risk markers, 64% of the pregnancies after surgery miscarried compared with 13% in those negative (P<0.005, RR for miscarriage=4.8, 95% CI= 1.3-18.0). CONCLUSION: The proposed risk HLA markers for unexplained recurrent miscarriage also seem to display a negative impact on pregnancy outcome in patients with recurrent miscarriages with Müllerian uterine anomalies.

Abortion, Habitual↗
PubMed1998

Studies on associations between human leukocyte antigen (HLA) class II alleles and antiphospholipid antibodies in Danish and Czech women with recurrent miscarriages.

Autoantibody production is commonly associated with particular HLA class II phenotypes. The aim of the present study was to investigate whether the presence of antiphospholipid (APL) antibodies and other autoantibodies in women with unexplained recurrent miscarriage was associated with particular human leukocyte antigen (HLA)-DR or -DQ alleles or linked epitopes which have previously been reported as being associated with the recurrent miscarriage syndrome or the presence of APL. In a total of 123 Danish and Czech women with recurrent miscarriage, serum was investigated for six different APL antibodies including anticardiolipin (ACL) antibody. Antinuclear antibodies (ANA), anti-zona pellucida antibodies and anti-sperm antibodies were also investigated. The women were HLA-DR and -DQ typed by DNA-based methods. The frequency of HLA-DR phenotypes did not differ significantly between APL antibody positive recurrent miscarriage patients and APL antibody negative recurrent miscarriage patients or healthy controls. Among ACL antibody positive recurrent miscarriage patients, significantly more were positive for the HLA-DR3 phenotype and negative for the HLA-DR2 phenotypes compared with healthy controls (P < 0.05). Among ANA positive recurrent miscarriage women, 55% carried the HLA-DR3 phenotype compared with 28% of ANA negative patients (P < 0.05) and 21% of healthy controls (P < 0.002). In conclusion, among recurrent miscarriage women, the HLA-DR3 phenotypes seem to predispose to formation of ACL antibodies and ANA. The association between APL antibodies and particular HLA alleles and HLA-linked epitopes reported in studies of patients with lupus erythematosus (e.g. HLA-DR7 and -DR4) could not be confirmed in patients with recurrent miscarriage.

Abortion, Habitual↗
PubMed1998

HLA-DR typing of women with recurrent late spontaneous abortion and unsuccessful cervical cerclage.

The release of certain cytokines, e.g. tumour necrosis factor (TNF)-alpha, in the amniotic fluid has been suggested to be a cause of preterm birth. The predisposition to excessive liberation of cytokines from peripheral leukocytes has been shown to depend partly on the individual's HLA-DR genotype. The HLA-DR1 and -DR3 alleles have previously been reported as being associated with a TNF-alpha high responder status and have also been associated with unexplained recurrent spontaneous abortions. In the present study, HLA-DR typing was performed in 10 women who had experienced recurrent very early preterm births resulting in perinatal death, or late spontaneous abortions under a clinical picture resembling that traditionally attributed to cervical incompetence. All patients had had at least one mid-trimester miscarriage in spite of the insertion of a cervical cerclage. Nine out of 10 (90%) patients had the HLA-DR phenotypes DR1 and/or DR3 compared with 37% in the background population (P < 0.005). The results suggest that HLA-DR-associated immunological factors might play a part in recurrent late spontaneous abortions and extremely preterm births under a cervical incompetence-like picture, at least in the subset of cases not treatable by cervical cerclage.

Abortion, Habitual↗
PubMed1998

HLA-E polymorphism in patients with recurrent spontaneous abortion.

The aim of this study was to compare the frequencies of five HLA-E alleles in 82 women with recurrent spontaneous abortions with that of 150 random Danish controls. PCR sequence-specific oligonucleotide typing was carried out to detect polymorphism in exons 2 and 3 of the HLA-E gene. In informative samples sequencing of these two exons was also undertaken to confirm the presence of the HLA-E*01031 allele. HLA-E*0101, HLA-E*01032 and HLA-E*01031 were detected with frequencies of 56.7%, 33.6% and 9.6% in controls and 58,5%, 32.9% and 8.5% in patients with recurrent abortion, respectively. No HLA-E*0102 and E*0104 alleles could be detected. Since the HLA-E allele distribution was similar in women with recurrent spontaneous abortion and controls, it is suggested that maternal HLA-E polymorphism per se does not play any role in the pathogenesis of this disorder of pregnancy.

Abortion, Habitual↗
PubMed1998

Intravenous immunoglobulin in the prevention of recurrent spontaneous abortion: the European experience.

PROBLEM: Clinical trials of the use of intravenous immunoglobulin (IvIg) in the treatment of recurrent spontaneous abortion (RSA) in Europe were reported and discussed. METHOD OF STUDY: A search of the published literature, combined with our own published and unpublished results, was performed. RESULTS: Two placebo-controlled trials have been concluded in Europe. One trial found high but equal success rates in both the IvIg and the placebo group. Another trial found that IvIg treatment may increase the success rate by 24% compared with placebo but that the result was not statistically significant, which might be due to the small number of patients. Reasons for the diverse results of the two trials were discussed. CONCLUSION: More and larger placebo-controlled trials of IvIg treatment in RSA are needed before drawing definitive conclusions.

Abortion, Habitual↗
PubMed1998

Is the expression of classical HLA class I antigens on trophoblast of importance for human pregnancy?

PROBLEM: Human leukocyte antigen (HLA)-C and possibly also HLA-B seem to be expressed on the extravillous trophoblast. These antigens carry epitopes that function as ligands for natural killer (NK)-cell-inhibitory receptors. Antitrophoblast cytotoxicity mediated by decidual NK cells might be involved in miscarriage. We thus found it relevant to elucidate whether parental HLA-C and -Bw polymorphism play a role in recurrent miscarriage (RM). METHOD OF STUDY: HLA-C and -Bw investigations by DNA-based techniques were undertaken in 35 couples with unexplained RM and in 30 couples with normal fecundity. The number of HLA-C- and -Bw-related supertypic specificities that can bind NK-cell-inhibitory receptors was evaluated in selected couples. RESULTS: The proportions of couples with RM and control couples carrying four HLA-C alleles with the same NK-cell-inhibitory supertypic specificities were equal. In 46% of studied couples with RM, all four HLA-B alleles carried the HLA-Bw6 supertypic specificity, which was significantly higher than the corresponding frequency (17%) in the control couples (P < 0.02). CONCLUSIONS: The expression of polymorphic HLA-C on trophoblasts does not seem to play a role in RM. Assuming that HLA-B is expressed on trophoblasts, we may suggest that the revealed predominance of HLA-Bw6 expression (which excludes the presence of HLA-Bw4-protective antigens) may predispose a particular couple to the RM phenomenon.

Abortion, Habitual↗
PubMed1997

HLA-C and -Bw typing of couples with unexplained recurrent miscarriages.

There is now evidence that the classical HLA class I molecule HLA-C is expressed on extravillous trophoblasts together with non-classical HLA-G molecules. Since clones of NK-cells are inhibited differently by supertypic epitopes associated with HLA-C and -B alleles we found it of interest to study HLA-C and -Bw polymorphism in 35 couples with recurrent miscarriage and 30 control couples with normal fecundity. All HLA assignments were undertaken by DNA techniques. The distribution of HLA-C alleles or the HLA-C associated supertypic epitopes recognized by NK1 or NK2 clones was not significantly different between patients and controls. The distribution of couples according to the number of NK1 and NK2 epitopes in the couple was similar in patients and controls. With respect to the HLA-Bw epitopes recognized by NKB1 clones, in 46% of the couples with recurrent miscarriage none of the spouses carried the HLA-Bw4 epitope compared with only 17% of the control couples (P < 0.02). It is concluded that the HLA-Bw4 epitope is carried more frequently by couples with normal fecundity than couples with recurrent miscarriage. The fetuses of couples with recurrent miscarriage are thus expected to lack expression of HLA-Bw4 epitopes on the trophoblast more often than fetuses of normal couples which might be of importance for the inhibition of NK-cell mediated antitrophoblast cytotoxicity.

Abortion, Habitual↗
PubMed1997

[Habitual abortion. A review of etiology, diagnosis and treatment with emphasis on immunonological factors].

Almost 1% of women who attempt pregnancy will experience recurrent miscarriage. The majority of traditionally accepted causes of recurrent miscarriage lack proper documentation and the evidence for the majority of treatments is sparse. An increased level of midfollicular phase luteinizing hormone seems to be associated with some cases of recurrent miscarriage. Many autoantibodies are found with increased frequency in women with recurrent miscarriage, and they seem to be associated with an increased risk of adverse pregnancy outcome. This may indicate that the autoantibodies per se or associated immunological phenomena are risk factors for the condition. Polygenically determined immunological phenomena seem to play an important role. Treatment of recurrent miscarriage by anticoagulation, allogeneic lymphocyte immunization or intravenous immunoglobulin is under evaluation in controlled trials.

Abortion, Habitual↗