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H Julkunen

Publications and source records attributed to H Julkunen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Congenital heart block: HLA differences between affected children and healthy siblings in four Finnish families.

Congenital heart block without intracardiac anatomic malformations is a potentially lethal disease affecting children and newborns. The mother often has an autoimmune disorder with autoantibodies against SS-A/Ro and/or SS-B/La antigens. However, only a minority of the children of these mothers develop complete heart block. It is believed that the maternal antibodies are pathogenic, but other immunological mechanisms such as cell-mediated injury cannot be excluded. Maternal cells may recognize fetal antigens adjacent to fetal HLA, and thus some children may be more susceptible to heart block than others, depending on their HLA genetics. The purpose of this study was to evaluate whether there are HLA differences between children with heart block and their healthy siblings. Six affected children in four families and their siblings were studied. MHC class I were typed serologically and class II and some non-HLA alleles were typed by DNA techniques. DQB1*03/04 were seen more often in the affected children than in the siblings. Some other differences were also seen in the other antigens of the MHC area.

Alleles↗
PubMed1997

Thrombolysis for acute ischemic stroke in the primary antiphospholipid syndrome.

Successful intravenous thrombolytic treatment for acute major ischemic stroke was given to a 24-year-old woman with primary antiphospholipid syndrome. Our patient was a smoker and used oral contraceptives containing estrogen at the time of the stroke. We discuss risk factors for stroke and the treatment of arterial thrombosis in patients with antiphospholipid antibodies.

Adult↗
PubMed1996

Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus.

There is accumulating evidence that anti-phospholipid (aPL) antibodies in the sera of patients with autoimmune diseases bind to a complex of anionic phospholipids and plasma phospholipid-binding proteins, namely beta 2-glycoprotein I (beta 2-GPI) and prothrombin. It has been suggested that a conformational change in beta 2-GPI, induced by binding either to anionic phospholipids or to the oxygen molecules on the irradiated microtiter plate, reveals cryptic antigenic epitope(s) in the native protein. We used an enzyme-linked immunoassay for measuring antibodies against two phospholipid-binding proteins, i.e., beta 2-GPI and prothrombin, absorbed to an irradiated plate in an unselected series of 139 patients with systemic lupus erythematosus (SLE). Elevated levels of antibodies against beta 2-GPI were found in 49% of patients and antibodies against prothrombin in 34% of patients. Both antibodies were significantly associated with deep venous thrombosis in patients with SLE (P = 0.009 for both antibodies). Accordingly, testing of these antibodies seems to be clinically useful in evaluating the risk of thrombosis.

Adolescent↗
PubMed1995

Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with systemic lupus erythematosus and primary Sjögren's syndrome.

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 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%; RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P = 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 (P = 0.0001-0.0014). With regard to SS-B/La, the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Isolated congenital heart block. Long-term outcome of mothers and characterization of the immune response to SS-A/Ro and to SS-B/La.

OBJECTIVE: To study the long-term outcome of mothers of children with isolated congenital heart block (CHB) and to characterize the maternal autoantibody response to SS-A/Ro and SS-B/La. METHODS: A retrospective clinical study of 33 mothers a mean of 11.2 years (SD 9.2 years, range 0-32 years) after the delivery of their first child with CHB. A clinical and immunologic study of 31 of these mothers, compared with 89 healthy mothers, 45 mothers with systemic lupus erythematosus (SLE), and 19 mothers with primary Sjögren's syndrome (SS), all of whom had healthy children. The specificity of the autoantibody responses to SS-A/Ro and SS-B/La was studied by enzyme-linked immunosorbent assays using purified human recombinant antigens and affinity-purified antigens. RESULTS: By the time of the analysis, 2 (6%) of the 33 mothers of CHB children had died and 6 (18%) had met the criteria for SLE. As a group, mothers of CHB children had clinical and immunologic characteristics more closely related to primary SS than to SLE or any other connective tissue disease. The predominant autoantibody response was to the SS-A/Ro antigens, notably to the 52-kd SS-A/Ro protein (prevalence 97%). Compared with controls with SLE, mothers of CHB children had higher titers of antibodies to recombinant 52-kd and 60-kd SS-A/Ro proteins and to the affinity-purified SS-A/Ro antigen (P < 0.05, P < 0.01, and P < 0.001, respectively). Compared with controls with primary SS, the autoantibody responses were similar. CONCLUSION: The predominant autoimmune disorder in mothers of children with CHB is subclinical primary SS. Antibodies to SS-A/Ro appear to be a prerequisite for the development of CHB.

Adolescent↗
PubMed1993

Congenital heart block in one of the HLA identical twins.

A case of HLA identical twins with one affected by congenital heart block is reported. Both twins, as their mother, had more than 12-fold higher anti-Ro antibody titers compared to healthy controls, but no differences were observed between the affected and the healthy baby. It is possible that there is a third factor causing the manifestation of this disease.

Adult↗
PubMed1993

Fetal outcome in lupus pregnancy: a retrospective case-control study of 242 pregnancies in 112 patients.

Fetal outcome in systemic lupus erythematosus (SLE) was retrospectively analysed in 242 pregnancies in 112 unselected patients, and the outcome was compared with that of 417 pregnancies in 192 control women matched for age, parity and socio-economic status. Relative risk for fetal loss after the diagnosis of SLE was 2.5 (95% confidence interval (CI), 1.4-4.5), for prematurity 5.8 (3.2-10.5) and for intra-uterine growth retardation (IUGR) 8.6 (3.0-24.3). Fetal outcome of pregnancy in patients with pre-existing stable lupus nephritis was no worse than in other SLE pregnancies. Relations of three lupus anticoagulant (LA) assays and tree anticardiolipin (aCL) enzyme-linked immunosorbent assays to fetal outcome were studied. Patients positive by any LA assay had a previous fetal loss more often than patients negative by all LA assays (odds ratio 3.4; 95% CI, 1.3-9.0; P = 0.01). Of the 41 patients whose antiphospholipid antibody (aPL) tests were all negative, five (12%) had a history of fetal loss (16% in controls). As a group, aCL was more sensitive for fetal loss than LA (64% vs 50%), but LA was more specific (77% vs 52%). Combinations of one aCL assay with one LA assay had a 41-73% sensitivity and a 64-73% specificity for a history of fetal loss. aPL did not correlate to prematurity or fetal growth retardation. In conclusion, fetal loss in SLE is 2.5 times more prevalent than in the normal population. The presence of LA indicates a high risk for fetal loss, and the absence of aPL is an indication of a favorable pregnancy outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy losses associated with antiphospholipid antibodies.

The effects of high dose iv-immunoglobulin on antiphospholipid antibody levels and on pregnancy outcome was studied in one patient with secondary (SLE) and two patients with primary antiphospholipid syndrome during their four pregnancies. These three women had had two pulmonary embolies related to pregnancy and estrogen containing pills, 13 miscarriages and only one liveborn after pre-eclamptic pregnancy. During the four pregnancies the patients also received 75 mg of aspirin per day. Progressive depression of IgG-anticardiolipin antibody titer was observed after repetitive high dose iv-immunoglobulin (1 g/kg body-weight) infusions. The effects on lupus anticoagulant were variable. Three pregnancies ended in a delivery of healthy child after 36-38 weeks of gestation and one preterm child (34 weeks), with slight respiratory distress syndrome, was born. Our results support the idea that the addition of iv-immunoglobulin to aspirin prophylaxis is worth considering when the patient has a severe antiphospholipid syndrome and/or is refractory to usual treatments.

Abortion, Spontaneous↗
PubMed1993

Pregnancy in lupus nephropathy.

The purpose of this study was to obtain information about the fetal and maternal outcome of pregnancy in patients with pre-existing lupus nephritis and to evaluate risk factors for poor fetal outcome. Twenty-six pregnancies in 16 patients were retrospectively analyzed. Induced abortions were performed in two patients and one patient had a spontaneous abortion. Of the 23 completed pregnancies, all clinically established on inactive lupus nephritis with normal renal function, seven (30%) were complicated by pre-eclampsia. Two of the three patients with severe pre-eclampsia had increased levels of antiphospholipid antibodies (aPL). Of the 23 newborns, seven (30%) were premature (< 37 weeks) and seven (30%) had neonatal complications. Six of the seven pregnancies associated with neonatal complications were hypertensive. There was one early neonatal death. Four newborns (16%) were severely growth retarded (< -2 SD). The presence of hypertension before pregnancy tended to correlate with low relative birth weight in the newborns (p = 0.079). Flares of systemic lupus erythematosus (SLE) during pregnancy and six months post partum occurred in two (9%) of the 23 completed pregnancies. Renal function was not affected irreversibly in any patient. Thus, the outlook for pregnancy in patients with stable lupus nephritis at conception is good. However, the risk of obstetric complications is greater and fetal morbidity, especially in hypertensive pregnancies, is common.

Abortion, Induced↗
PubMed1993

Production of prostacyclin and thromboxane in lupus pregnancies: effect of small dose of aspirin.

OBJECTIVES: To find out whether the tendency toward poor outcome in lupus pregnancies could be explained by changes in prostacyclin/thromboxane production, to relate these changes to the presence of antiphospholipid antibodies, and to study the potential benefits of low-dose aspirin. METHODS: We followed the urinary output of prostacyclin metabolites (6-keto-prostaglandin [PG]F1 alpha, 2,3-dinor-6-keto-PGF1 alpha) and thromboxane metabolites (thromboxane B2, 2,3-dinor-thromboxane B2) using high-pressure liquid chromatography followed by radioimmunoassay. We studied 14 pregnant women with systemic lupus erythematosus (SLE), of whom six had detectable antiphospholipid antibodies. The patients were randomized by a computerized program to receive either 50 mg aspirin daily (six women) or placebo (eight women). Nine healthy pregnant women served as controls. RESULTS: The production of prostacyclin was normal in early pregnancy in SLE patients but was reduced during late gestation in those without antiphospholipid antibodies. The production of thromboxane was increased in SLE patients compared with controls, and this increase was highest (two-to threefold rise) when antiphospholipid antibodies were detectable. Aspirin eliminated thromboxane dominance without affecting prostacyclin production. CONCLUSION: These data suggest that the presence of antiphospholipid antibodies in SLE patients may trigger thromboxane dominance, possibly contributing to the adverse outcome of these pregnancies. This thromboxane dominance can be eliminated with aspirin.

Adult↗
PubMed1993

Isolated congenital heart block: fetal and infant outcome and familial incidence of heart block.

OBJECTIVE: To determine the 1-year outcome of infants with isolated congenital heart block, the risk of fetal loss in mothers of affected infants, and the risk of recurrence of congenital heart block. METHODS: The outcomes of 34 infants with isolated congenital heart block and of the 109 pregnancies in the 32 mothers of these infants were analyzed retrospectively. A control group consisted of 170 pregnancies in 64 women individually matched for age, parity, and socioeconomic status. RESULTS: Five (15%) of the 34 infants with isolated congenital heart block died before 1 year of age. The relative risk for fetal loss in mothers of affected children, after the exclusion of a mother with 16 spontaneous abortions, was 1.9 (95% confidence interval 0.9-3.8; P = .094). The prevalence of congenital heart block in all siblings of children with congenital heart block was 4% (two of 45). The risk of having a child with congenital heart block after a previous birth of an affected child was 8% (two of 26). CONCLUSIONS: Infant mortality in isolated congenital heart block is considerable, and mothers of affected children tend to have an increased risk of fetal loss. However, the risk of recurrence of congenital heart block is low.

Abortion, Spontaneous↗
PubMed1992

Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus.

Patients with mixed connective tissue disease (MCTD, n = 32) or systemic lupus erythematosus (SLE, n = 60) were typed for HLA-A, B, C, Dw, and DR antigens. All patients with SLE fulfilled at least four criteria of SLE and the patients with MCTD met the criteria proposed by Alarcon-Segovia (1989). The presence of antibodies to Sm was not considered as an exclusion for MCTD. In the patients with SLE, Dw3, DR3, and the associated B8 and A1 antigens were increased, whereas in the patients with MCTD an increased frequency of Dw4 was found (45 v 18% in controls v 14% in SLE). Of the subtypes of DR4, Dw4 was present in all but one of the DR4 positive patients. The frequency of DR4 in patients with MCTD (52%) differed significantly from that of controls (28%). The strong association of MCTD to one DR4 subtype was further seen in the significantly increased frequency of the B15, DR4 combination. Thus the genetic background seems to be different in patients with MCTD from that in patients with SLE. This could partly explain the clinical differences between these diseases.

Female↗
PubMed1992

Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients.

The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG)-aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies.

Adolescent↗
PubMed1991

Congenital heart block: successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy.

In mothers with anti-Ro-positive antibodies whose previous pregnancies have ended in deliveries of infants with congenital heart block, prophylactic therapeutic strategies are used to try to diminish the production and passage into fetal circulation of autoantibodies. Intravenous gamma globulin was given at 14 and 18 weeks' gestation and prednisone was given from 14 weeks' gestation to a woman with Sjögren's syndrome. The pregnancy ended with delivery of an infant without congenital heart block.

Adult↗