8 results on '"Siren, M-K."'
Search Results
2. MATERNAL HLA ANTIGENS AND ANTIBODIES TO SS-A/RO AND SS-B/LA. COMPARISON WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND PRIMARY SJÖGREN’S SYNDROME
- Author
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JULKUNEN, H., primary, SIREN, M.-K., additional, KAAJA, R., additional, KURKI, P., additional, FRIMAN, C., additional, and KOSKIMIES, S., additional
- Published
- 1995
- Full Text
- View/download PDF
3. Role of HLA in congenital heart block: susceptibility alleles in mothers.
- Author
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Siren, M-K., Julkunen, H., Kaaja, R., Kurki, P., and Koskimies, S.
- Subjects
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CONGENITAL heart disease in children , *BIOMARKERS , *ANTIGENS , *SJOGREN'S syndrome , *MOTHER-child relationship - Abstract
In congenital heart block (CHB), abnormal maternal immunisation leads to autoantibody production against SS-A/Ro and SS-B/La antigens. These maternal antibodies are transferred across the placenta to the unborn child and are believed to transmit irreversible immunological injury in developing foetal heart tissue, thus causing 3rd-degree atrioventricular block. The mothers may suffer from systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (SS), but they may be asymptomatic. Women with primary SS show a typical autoimmune HLA antigen pattern, namely higher frequency of HLA B8 and DR3 than in the normal population. The HLA pattern may affect individual ability to resist infecting bacteria and viruses and to response in various ways to autoantigens. It is probable that other factors such as genetic regulation of immune response are involved in CHB. We compared the HLA class I and class II alleles of mothers having CHB children with those of women suffering from primary SS and having healthy children, and with those of healthy Finns. Antibodies against 52-kD and 60-kD SS-A/Ro and 48-kD SS-B/La antigens were compared between the two groups of mothers. Our results show that anti-SS-A/Ro antibody-positive mothers all show a strong association with known autoimmune-predisposing HLA alleles, however, the mothers of CHB children differ in some HLA class I alleles, and especially in HLA haplotypes, from mothers of healthy children. Mothers with HLA A1, Cw7, B8 and without B15 are at particularly high risk of having CHB children. [ABSTRACT FROM AUTHOR]
- Published
- 1999
4. Role of HLA in congenital heart block: susceptibility alleles in children.
- Author
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Siren, M-K., Julkunen, H., Kaaja, R., Ekblad, H., and Koskimies, S.
- Subjects
- *
CONGENITAL heart disease in children , *ALLELES , *MOTHER-child relationship , *CELLS - Abstract
Congenital heart block (CHB) is a syndrome of uncertain pathogenesis leading to cardiac conduction disturbances in the foetus and newborns. It has been proposed that maternal antibodies transmit immunological injury in the developing foetal heart, thus causing irreversible damage of the atrioventricular node, leading to third-degree atrioventricular block. However, some genetic or environmental factors may also be involved. We have searched for genetic markers that play a role in immune response and that would be pathognomonic for the disease, either in mothers by regulating their immune response or in children by affecting antigen presentation and target for the maternal immune response. We have compared HLA class I and II alleles of the children with their mother and with healthy individuals and searched for HLA markers that would be emphasized in children. We have shown that particular DQ alleles in the child predispose to CHB, perhaps serving as antigen-presenting molecules on site. In addition, the HLA-Cw3 allele is involved, although its function remains to be clarified. In our results, children with CHB were often identical to their mothers in alleles of DRB, DQA and DQB loci, thus affecting foetomaternal recognition and suggesting that cell-mediated mechanisms could be involved in the pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 1999
5. MATERNAL HLA ANTIGENS AND ANTIBODIES TO SS-A/RO AND SS-B/LA. COMPARISON WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND PRIMARY SJÖGREN’S SYNDROME.
- Author
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JULKUNEN, H., SIREN, M.-K., KAAJA, R., KURKI, P., FRIMAN, C., and KOSKIMIES, S.
- Abstract
To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more often than healthy controls [71 20%; relative risk (RR) 9.8, <0.00001 and 74 23% RR 9.8, <0.0001, respectively]. HLA B35 was protective (RR 0.1, = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, = 0.0057 and RR 3.1, = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, =0.010). In general, the HLA antigen profile in mothers of children with CHB was more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children with CHB than in controls with SLE and primary SS ( = 0.0001–-0.0014). With regard to SS-B/La, the autoantibody responses were similar ( = 0.32-0.66). HLA B8, DR3, DQ2 and heterozygosity for DQ1/DQ2 were strongly associated with all three assays for antibodies to SS-A/Ro ( =0.0001–0.018). The corresponding associations with antibodies to SS7-B/La were weaker ( = 0.0076–1.0). The common immunogenetic background of the mother for having a child with CHB is the presence of HLA antigens B8, DR3 and DQ2 associated with high levels of antibodies to SS7-A/Ro. Mothers of children with CHB are genetically more closely related to patients with primary SS than to patients with SLE. [ABSTRACT FROM PUBLISHER]
- Published
- 1995
- Full Text
- View/download PDF
6. Recurrent miscarriage, congenital heart block and systemic lupus erythematosus.
- Author
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Julkunen H, Kaaja R, and Siren MK
- Subjects
- Adult, Female, Heart Block diagnostic imaging, Heart Block therapy, Humans, Infant, Newborn, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic immunology, Pacemaker, Artificial, Pregnancy, Risk Factors, Ultrasonography, Prenatal, Abortion, Habitual etiology, Heart Block congenital, Lupus Erythematosus, Systemic complications, Pregnancy Complications drug therapy, Pregnancy Complications immunology
- Abstract
We report the obstetric history of a woman, who between 15 spontaneous abortions, gave birth to a child with congenital heart block. She later developed systemic lupus erythematosus, had antibodies to SS-A/Ro and SS-B/La but was repeatedly negative for antiphospholipid antibodies.
- Published
- 1999
- Full Text
- View/download PDF
7. Immune-mediated congenital heart block (CHB): identifying and counseling patients at risk for having children with CHB.
- Author
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Julkunen H, Kaaja R, Siren MK, Mack C, McCready S, Holthöfer H, Kurki P, and Maddison P
- Subjects
- Abortion, Spontaneous immunology, Abortion, Spontaneous prevention & control, Adult, Antibody Specificity, Autoantibodies analysis, Child, Enzyme-Linked Immunosorbent Assay, Female, Fetal Death immunology, Fetal Death prevention & control, Finland, Heart Block epidemiology, Humans, Incidence, Male, Pregnancy, Pregnancy Outcome, Prevalence, Recurrence, Retrospective Studies, Risk Factors, SS-B Antigen, Autoantigens immunology, Counseling, Heart Block congenital, Heart Block immunology, RNA, Small Cytoplasmic, Ribonucleoproteins immunology
- Abstract
Objective: To identify patterns of maternal antibodies associated with an increased risk of having a child with congenital heart block (CHB) and to provide a basis for counseling women with a previously affected child., Methods: This retrospective clinical study of the obstetric histories of 46 Finnish women with a CHB child compared the strength and specificity of the immune response to SS-A/Ro and SS-B/La, as determined by immunoblot and ELISA, in 44 affected women with 85 women with systemic lupus erythematosus (SLE) and 32 women with primary Sjögren's syndrome (SS) with healthy children., Results: High levels of anti-SS-A/Ro and anti-SS-B/La by practically all assays were associated with a significantly increased risk of having a CHB child. The best single test to identify high-risk mothers was anti-52 kd SS-A/Ro by immunoblot (OR 18.9), and it was the only assay to detect mothers at increased risk of CHB as compared with controls with primary SS. Low risk of CHB was indicated by undetectable or low levels of antibodies in the ELISA assays and no reactivity on immunoblot. Mothers with a previous child with CHB had a history of fetal loss (mostly spontaneous abortions) or a history of recurrent fetal losses (> or = 3) slightly more often than controls. Late-trimester obstetric complications in non-CHB pregnancies were insignificant. The relative risk for a female child compared with a male child to have CHB was 1.9 (1.2-2.9, P = .009), and the risk of the mother having another child with CHB was 12% (4 of 34)., Conclusion: Although there is no unique antibody profile specific for CHB, mothers with a high or low risk of having a child with CHB can be identified. Female children appear to have an increased risk of CHB, but the risk of the mother having another child with CHB is low.
- Published
- 1998
- Full Text
- View/download PDF
8. High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.
- Author
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Speiser DE, Tiercy JM, Rufer N, Grundschober C, Gratwohl A, Chapuis B, Helg C, Löliger CC, Siren MK, Roosnek E, and Jeannet M
- Subjects
- Alleles, Bone Marrow Transplantation immunology, Cause of Death, Female, Follow-Up Studies, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, HLA Antigens analysis, HLA Antigens immunology, Humans, Infections etiology, Infections mortality, Life Tables, Male, Survival Analysis, Survival Rate, Transplantation, Homologous immunology, Transplantation, Homologous mortality, Bone Marrow Transplantation mortality, Histocompatibility Testing methods
- Abstract
As compared with related HLA-identical sibling donors, bone marrow transplantation (BMT) with phenotypically HLA ABDR-compatible unrelated donors is associated with increased mortality. This may be due to hidden HLA incompatibilities not detected by conventional typing. We have analyzed 44 unrelated patient-donor pairs who were matched for HLA-A, -B, and -DR by routine tissue typing. Our comprehensive HLA typing approach consisted of serology, cytotoxic T-cell precursor (CTLp) tests, T-cell cloning, oligotyping, and DNA sequencing. Using these techniques, we identified numerous HLA allele mismatches not detected by the previously applied routine typing. Twenty-four patient-donor pairs were highly matched and had a low CTLp frequency, whereas the remaining 20 pairs were allele-mismatched for HLA-A, -B, -C, -DR, -DQ antigens and/or had a positive result of the CTLp test. Patient and donor age, diagnosis, and treatment did not differ significantly between the matched and mismatched transplants. The probability for severe acute graft-versus-host disease grades III-IV was 21% in the matched and 47% in the mismatched patients (P = .0464). Transplant-related mortality was 21% and 57% (P = .0072) and actuarial patient survival rates at 3 years were 61% and 13% (P = .0005). We conclude that both HLA class I and class II allele mismatches between unrelated phenotypically ABDR-compatible patient-donor pairs are frequent and associated with increased incidence of posttransplant complications.
- Published
- 1996
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