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Biomedical subjects

R M Silver

Publications and source records attributed to R M Silver.

At least 19 recordsLinked to original sources
PubMed2004

Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor.

OBJECTIVE: Microarray analysis was used to characterize the labor-selective transcriptome of the human myometrium during labor. One highly up-regulated transcript, monocyte chemotactic protein-1 (MCP-1), was further characterized. METHODS: Expression of MCP-1 was evaluated in the myometrium, the placenta, the gestational membranes (GM) and the amniotic fluid (AF) by real time RT-PCR, Northern blot analysis and ELISA. The level of immunoreactive (IR) MCP-1 content of primary myometrial cultures treated with inflammatory cytokines was quantified by ELISA. RESULTS: Up-regulation of the myometrial MCP-1 transcript in term laboring patients was demonstrated by microarray and confirmed by real time (RT)-PCR and Northern blot analysis. Increased MCP-1 transcripts were demonstrated in GM during term labor. The IR content of myometrial MCP-1 was increased during term labor and in the AF from patients experiencing preterm delivery. Levels of IR MCP-1 increased in myometrial cultures in response to interleukin 1-beta. CONCLUSION: The expression of myometrial MCP-1 was significantly increased during term labor and was similarly increased in vitro in response to interleukin 1-beta, a pro-inflammatory substance known to play a role in preterm birth. The increased IR content of MCP-1 within the AF preceding preterm delivery may render this protein a useful predictor of preterm birth.

Adult↗
PubMed2004

Histologic features of placentas and abortion specimens from women with antiphospholipid and antiphospholipid-like syndromes.

OBJECTIVE: Antiphospholipid syndrome is characterized by recurrent pregnancy loss, thrombosis, and antiphospholipid antibodies. However, some women with clinical features of antiphospholipid syndrome test negative for antiphospholipid antibodies ("antiphospholipid-like syndrome"). Women with antiphospholipid and antiphospholipid-like syndromes have serum immunoglobulin G that harms murine pregnancy, suggesting that the mechanisms of fetal death may be similar in both groups. The objective of our study was to determine whether patients with antiphospholipid and antiphospholipid-like syndromes share pathophysiology by comparing the histology of gestational tissues from these groups. METHODS: Placenta and abortion specimens were obtained from 44 pregnancies in 26 women with antiphospholipid syndrome and 37 pregnancies in 21 women with antiphospholipid-like syndrome. Of these, 16 pregnancies with antiphospholipid syndrome and 8 with antiphospholipid-like syndrome were treated with a variety of medications intended to improve pregnancy outcome. Placentas from 31 elective pregnancy terminations and 40 pregnancies complicated by idiopathic preterm delivery served as an additional control group. Twenty histologic parameters were systematically assessed by a single investigator who was blinded to the clinical status of the specimens. Histopathologic findings were compared among groups using multivariate logistic regression analysis. RESULTS: Antiphospholipid syndrome pregnancies included 15 spontaneous abortions, 13 fetal deaths, and 16 live births. Pregnancies in the antiphospholipid-like syndrome group resulted in 5 spontaneous abortions, 30 fetal deaths, and one live birth. Gestational tissues from antiphospholipid and antiphospholipid-like syndrome pregnancies were similar for every histologic feature tested. Decidua from women with both antiphospholipid and antiphospholipid-like syndromes had more necrosis, acute and chronic inflammation, and vascular thrombus compared to controls. Placental tissue from antiphospholipid and antiphospholipid-like syndrome pregnancies showed more infarction, intravascular fibrin deposition, syncytial knot formation, and fibrosis than controls. Histologic features were variable within groups. There were no histologic differences in tissues from live births and pregnancy losses, or in treated and untreated pregnancies. CONCLUSIONS: Placental histopathology is similar in antiphospholipid and antiphospholipid-like syndrome pregnancies, suggesting that these disorders may share pathophysiology. Histologic findings in women with APS are non-specific and may not differentiate between women with APS and APS-like syndromes.

Abortion, Spontaneous↗
PubMed2001

Thrombin differentiates normal lung fibroblasts to a myofibroblast phenotype via the proteolytically activated receptor-1 and a protein kinase C-dependent pathway.

Myofibroblasts are ultrastructurally and metabolically distinctive fibroblasts that express smooth muscle (SM)-alpha actin and are associated with various fibrotic lesions. The present study was undertaken to investigate the myofibroblast phenotype that appears after activation of normal lung fibroblasts by thrombin. We demonstrate that thrombin induces smooth muscle-alpha actin expression and rapid collagen gel contraction by normal lung fibroblasts via the proteolytically activated receptor-1 and independent of transforming growth factor-beta pathway. Using antisense oligonucleotides we demonstrate that a decreased level of PKCepsilon abolishes SM-alpha actin expression and collagen gel contraction induced by thrombin in normal lung fibroblasts. Inhibition of PKCepsilon translocation also abolishes thrombin-induced collagen gel contraction, SM-alpha actin increase, and its organization by normal lung fibroblasts, suggesting that activation of PKCepsilon is required for these effects. In normal lung fibroblasts PKCepsilon binds to SM-alpha actin after thrombin treatment, but in activated fibroblasts derived from scleroderma lung they associate even in untreated cells. This suggests that SM-alpha actin may serve as a substrate for PKCepsilon in lung fibroblasts when activated by thrombin. We propose that thrombin differentiates normal lung fibroblasts to a myofibroblast phenotype via a PKC-dependent pathway. Thrombin-induced differentiation of normal lung fibroblasts to a myofibroblast phenotype resembles the phenotype observed in scleroderma lung fibroblasts. Therefore, we conclude that chronic exposure to thrombin after microvascular injury leads to activation of normal lung fibroblasts and to the appearance of a myofibroblast phenotype in vivo. Our study provides novel, compelling evidence that thrombin is an important mediator of the interstitial lung fibrosis associated with scleroderma.

Actins↗
PubMed2001

Depletion of protein kinase Cepsilon in normal and scleroderma lung fibroblasts has opposite effects on tenascin expression.

OBJECTIVE: To determine whether the extracellular matrix protein tenascin-C (TN-C) is overexpressed in lung fibroblasts from systemic sclerosis (SSc) patients, the molecular mechanisms regulating TN-C secretion in SSc and normal lung fibroblasts, and how these processes might contribute to lung fibrosis in SSc patients. METHODS: TN-C secretion by SSc and normal fibroblasts was compared in vivo (in bronchoalveolar lavage [BAL] fluid) and in vitro (in culture medium). The ability of thrombin to induce TN-C was confirmed at both the protein and the messenger RNA (mRNA) level. The role of protein kinase Cepsilon (PKCepsilon) in the expression of TN-C was evaluated by determining the effects of thrombin on PKCepsilon levels and by directly manipulating PKCepsilon levels via the use of antisense oligonucleotides. RESULTS: BAL fluid from SSc patients contained high levels of TN-C, whereas that from normal subjects contained little or no TN-C. In vitro, SSc lung fibroblasts expressed much higher amounts of TN-C than did normal lung fibroblasts. Consistent with the idea that thrombin is a physiologic inducer of TN-C, thrombin stimulated TN-C mRNA and protein expression in both SSc and normal lung fibroblasts by a mechanism that required proteolytic cleavage of the thrombin receptor. Surprisingly, thrombin treatment and antisense oligonucleotide-mediated depletion of PKCepsilon indicated that TN-C expression is regulated via opposite signaling mechanisms in SSc and normal cells. In SSc lung fibroblasts, thrombin decreased PKCepsilon levels, and the decreased PKCepsilon induced TN-C secretion; in normal fibroblasts, thrombin increased PKCepsilon levels, and the increased PKCepsilon induced TN-C secretion. Normal and SSc lung fibroblasts also differed in the subcellular localization of PKCepsilon, both before and after thrombin treatment. CONCLUSION: These studies are the first to demonstrate that thrombin is a potent simulator of TN-C in lung fibroblasts and that PKCepsilon is a critical regulator of TN-C protein levels in these cells. Furthermore, our results indicate that both the regulation of PKCepsilon levels by thrombin and the regulation of TN-C levels by PKCepsilon are defective in SSc lung fibroblasts.

Blotting, Northern↗
PubMed2001

Heparin-induced thrombocytopenia is rare in pregnancy.

OBJECTIVE: The indications for heparin use during pregnancy are expanding; however, heparin is associated with serious adverse effects including heparin-induced thrombocytopenia. Low-molecular-weight heparin is expensive but is associated with less frequent occurrences of heparin-induced thrombocytopenia in the nonpregnant population. However, the incidence of heparin-induced thrombocytopenia during pregnancy is unknown. The purpose of this study was to compare the incidence of heparin-induced thrombocytopenia in pregnant and nonpregnant women. STUDY DESIGN: This is a retrospective cohort comparison. Pregnant and nonpregnant women were identified by means of diagnosis related group and Current Procedural Terminology code searches at three medical centers in Utah; the incidence of heparin-induced thrombocytopenia in the two groups was compared. RESULTS: There were 10 (4%) cases of thrombocytopenia among 244 heparin-treated pregnant patients and 26 (11%) cases among the 244 nonpregnant controls. There were no cases of heparin-induced thrombocytopenia in the pregnant group, but there were 10 (4%) cases in the control group (P =.0014). CONCLUSION: Heparin-induced thrombocytopenia is extremely rare in pregnant women.

Adult↗
PubMed2001

Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death.

OBJECTIVE: Studies in rheumatologic populations suggest that immunoglobulin A antiphospholipid antibodies are strongly associated with the clinical manifestations of antiphospholipid syndrome. However, the association between immunoglobulin A antiphospholipid antibodies and pregnancy loss is uncertain. We determined whether immunoglobulin A antiphospholipid antibodies, specifically anti-beta(2)-glycoprotein I and anticardiolipin, are associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 133 women who experienced unexplained recurrent spontaneous abortion, (2) 48 women who experienced unexplained fetal death, (3) 145 healthy fertile control subjects, and (4) 67 women with well-characterized antiphospholipid syndrome. Serum immunoglobulin A, immunoglobulin G, and immunoglobulin M anti-beta(2)-glycoprotein I and anticardiolipin antibodies were determined by enzyme-linked immunoassay. RESULTS: Groups of women who experienced unexplained recurrent spontaneous abortion and unexplained fetal death had a higher proportion of women who had positive test results for immunoglobulin A anti-beta(2)-glycoprotein I antibodies than fertile control subjects (P < .01, chi-square test); these subjects also had higher levels of autoantibody (P = .001, Kruskal-Wallis). Women who experienced recurrent spontaneous abortion had a higher proportion of women with positive test results for immunoglobulin A anticardiolipin antibodies compared to fertile control subjects (P < .05, chi-square test); this group also had higher levels of autoantibody (P = .0065, Kruskal-Wallis test). Linear regression analysis showed significant correlation between anti-beta(2)-glycoprotein I immunoglobulin A and anti-beta(2)-glycoprotein I immunoglobulin G (R = .609; P =.0001) and less correlation between anticardiolipin immunoglobulin A and anticardiolipin immunoglobulin G (R = .093; P = .065). CONCLUSION: Immunoglobulin A anti-beta(2)-glycoprotein I antibodies are more common in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death whose initial test results are negative for lupus anticoagulant and immunoglobulin G anticardiolipin antibodies compared to fertile control subjects. Therefore, these antibodies may identify additional women with clinical features of antiphospholipid syndrome who are not identified through traditional testing. It is unclear whether these antibodies are directly pathogenic, a result of the pregnancy losses, or markers for an underlying, yet uncharacterized autoimmune disorder.

Abortion, Habitual↗
PubMed2001

Anti-fibrillin-1 autoantibodies in systemic sclerosis are GM and KM allotype-restricted.

GM and KM allotypes--genetic markers of immunoglobulin (Ig) gamma and kappa chains, respectively--have been shown to play an important role in genetic predisposition to some autoimmune diseases. To determine their role in susceptibility to systemic sclerosis (SSc; scleroderma) and in the generation of anti-fibrillin-1 antibodies, 148 SSc patients and 191 controls were typed for several GM and KM allotypes by a standard hemagglutination inhibition method. IgG and IgM antibodies to fibrillin-1 were measured by radioimmunoassay. GM and KM phenotypes were not significantly associated with SSc. However, these determinants significantly influenced the production of anti-fibrillin-1 antibodies in SSc patients. In Caucasians, GM1,3,17 23 5,13,21 and GM3 23 5,13 phenotypes were associated with the presence and absence of IgG autoantibodies, respectively. The production of these autoantibodies was also associated with KM allotypes, KM1,3 heterozygosity being associated with response and homozygosity for the KM3 allele with nonresponse to fibrillin-1. In African-Americans, the KM1 homozygotes were associated with the absence of anti-fibrillin-1 antibodies and the KM3 homozygotes with the presence of autoantibodies. In this ethnic group, the GM1,17 5,13 phenotype was associated with the absence of IgM autoantibodies. This represents the first description of genetic control of autoimmunity to fibrillin-1 in scleroderma.

Autoantibodies↗
PubMed2001

Hospital admissions, length of stay, charges, and in-hospital death among patients with systemic sclerosis.

OBJECTIVE: To investigate population hospitalization rates to community hospitals for systemic sclerosis (SSc, scleroderma) and examine whether age, sex, race, and insurance status independently predict length of stay (LOS), hospital charges, and in-hospital death. METHODS: The 1995 Healthcare Cost and Utilization Project national inpatient sample was used to identify 3,621 SSc hospitalizations. Weighted age, sex, and race-specific frequencies were divided by population estimates to calculate hospitalizations per million people. Regression models were used to model LOS, charges, and in-hospital death with age, sex, race, and insurance serving as the primary independent variables. Covariates included numbers of diagnoses and procedures, whether or not the admission was a transfer from another hospital, and the presence of comorbid conditions. RESULTS: Population hospitalization rates were higher for non-whites compared to whites among those < 65, while rates were higher for whites compared to non-whites for those > or =65 years old. On average, non-whites were at least 10 years younger than whites. The mean LOS was 7.5 days, with whites' average LOS being 10% shorter than non-whites', and patients with public health insurance having approximately 9% longer LOS than those with private insurance. Charges averaged almost US$15,000 per hospitalization (median = $8,441), amounting to $280 million in community hospital charges in the U.S. in 1995. The overall in-hospital death rate was 7.1%. CONCLUSION: These patterns are consistent with a greater burden and increased severity of disease among non-whites under age 65 with Ssc.

Adolescent↗
PubMed2000

A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.

OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at </=12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 +/- 1.1 weeks; placebo group, 36.7 +/- 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 +/- 186.1 g; placebo group; 2604.4 +/- 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.

Adult↗
PubMed2000

Recurrent pregnancy loss: summary and clinical recommendations.

Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive pregnancy losses before 20 weeks of gestation. This problem occurs in approximately 1% of all couples and is a frustrating problem for both the patient and physician. This article provides an overview of the problem, including causes, treatments, and recommendations. Among the numerous proposed causes of RPL, only parental karyotype abnormalities, antiphospholipid syndrome, uterine malformations, and cervical incompetence are universally accepted. There are numerous treatments for RPL, but only the efficacy of heparin and low-dose aspirin in women with antiphospholipid syndrome has been established with properly controlled trials. Even after undertaking a complete evaluation, the cause of RPL remains uncertain in over 50% of cases. These patients should understand that subsequent pregnancies have up to a 70% chance of success without treatment.

Abortion, Habitual↗
PubMed2000

Neonatal alloimmune thrombocytopenia: antenatal management.

OBJECTIVE: The optimal management of pregnancies at risk for neonatal alloimmune thrombocytopenia is debated. Proposed management includes the administration of intravenous immunoglobulin and serial determination of the fetal platelet count. The aims of our study were to determine the effectiveness and likely mechanism of action of intravenous immunoglobulin and to evaluate the safety of cordocentesis in cases of neonatal alloimmune thrombocytopenia. STUDY DESIGN: Eighteen mother-infant pairs were studied. All were at risk for neonatal alloimmune thrombocytopenia on the basis of delivery of a previously affected infant and confirmation of specific maternal antiplatelet antibodies. The pertinent antigen was HPA-1a in 13 cases, HPA-3a in 2 cases, and undetermined in 3 cases. Serial cordocenteses were used to determine fetal platelet counts. If the platelet count was <50,000/microL before 37 weeks' gestation, treatment was initiated with intravenous immunoglobulin administered to either the fetus (n = 2) or the mother (n = 8). In 3 cases fetal and maternal immunoglobulin G levels were determined before and after treatment. RESULTS: Seven (39%) fetuses had adequate platelet counts, were not treated, and were delivered of infants with normal platelet counts. Eleven (61%) fetuses were thrombocytopenic. Eight thrombocytopenic infants were treated with maternally administered intravenous immunoglobulin. In 6 (75%) of 8 cases the fetal platelet count increased after administration of intravenous immunoglobulin, but 2 fetuses remained severely thrombocytopenic. Two thrombocytopenic fetuses were treated with intravenous immunoglobulin infusion directly into the umbilical vein; both remained thrombocytopenic. Moreover, fetal immunoglobulin G levels did not correlate well with the response to intravenous immunoglobulin. Two (5.3%) of 38 cordocenteses were complicated by hemorrhagic complications, necessitating immediate cesarean delivery despite the use of prophylactic platelet transfusion in one case. CONCLUSION: Severe fetal alloimmune thrombocytopenia does not always occur in subsequent fetuses. Thus either fetal antigen status or platelet counts or both of these are necessary to determine whether treatment is needed. The effect of intravenous immunoglobulin on raising the fetal platelet count is inconsistent and appears to be caused by maternal or placental factors rather than a direct inhibition of fetal platelet destruction by immunoglobulin. The risk of hemorrhagic complications from cordocentesis in pregnancies complicated by neonatal alloimmune thrombocytopenia is higher than generally appreciated and is not always avoided by platelet transfusion at the time of the procedure.

Antigens, Human Platelet↗
PubMed2000

Systemic sclerosis: environmental and occupational risk factors.

There is growing concern about the association between systemic sclerosis and certain environmental and occupational risk factors, including exposures to vinyl chloride, adulterated cooking oils, L-tryptophan, silica, silicone breast implants, organic solvents, and other agents such as epoxy resins, pesticides, and hand/arm vibration. This article highlights the current medical research that has examined these associations in scleroderma-like disorders and in systemic sclerosis.

Environmental Exposure↗
PubMed2000

Thrombin upregulates interleukin-8 in lung fibroblasts via cleavage of proteolytically activated receptor-I and protein kinase C-gamma activation.

Acute and chronic interstitial lung diseases are accompanied by evidence of inflammation and vascular injury. Thrombin activity in bronchoalveolar lavage fluid from such conditions is often increased, as well as interleukin (IL)-8. We observed that conditioned medium from lung fibroblasts exposed to thrombin has chemotactic activity for polymorphonuclear cells, and that this activity can be abolished by antibody to IL-8. We report that thrombin stimulates expression of IL-8 in human lung fibroblasts on both the messenger RNA and protein levels in a time- and dose-dependent manner. Stimulation of IL-8 expression by thrombin is inhibited by specific thrombin inhibitors. Synthetic thrombin receptor agonist peptide-14 mimics thrombin's stimulation of IL-8 expression in a dose-dependent manner consistent with the idea that upregulation of IL-8 by thrombin in human lung fibroblasts requires cleavage of proteolytically activated receptor-I. We demonstrate further that thrombin-induced IL-8 synthesis is regulated by protein kinase (PK) C. PKC-gamma may be involved in the upregulation of lung fibroblast IL-8 by thrombin because stimulation of lung fibroblasts with thrombin caused significant upregulation of PKC-gamma and because PKC-gamma antisense oligonucleotides inhibited the accumulation of PKC-gamma protein and IL-8 protein. Our data suggest that the PKC-gamma isoform increase observed after thrombin stimulation is required for thrombin-induced IL-8 formation by human lung fibroblasts.

Base Sequence↗
PubMed1999

Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases.

A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gene has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of anti-fibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjögren's syndrome). Ab specificity for fibrillin-1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.

Adult↗
PubMed1999

Anti-beta2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome.

OBJECTIVE: Studies in rheumatologic and hematologic populations suggest that anti-beta(2)-glycoprotein I antibodies are more specific for the clinical manifestations of antiphospholipid syndrome than anticardiolipin antibodies. However, the association between anti-beta(2)-glycoprotein I and pregnancy loss remains uncertain. We sought to determine whether anti-beta(2)-glycoprotein I is associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 152 healthy fertile control subjects, (2) 141 subjects with unexplained recurrent spontaneous abortions, (3) 58 subjects with unexplained fetal deaths, and (4) 73 subjects with well-characterized antiphospholipid syndrome. Serum anticardiolipin and anti-beta(2)-glycoprotein I levels were determined by enzyme-linked immunoassay. RESULTS: Patients with antiphospholipid syndrome had significantly higher levels of immunoglobulin G and immunoglobulin M anticardiolipin and anti-beta(2)-glycoprotein I than the other 3 groups (P <.0001). However, women in the recurrent spontaneous abortion, fetal death, and fertile control groups had similar levels of each antibody. Similarly, there were no differences in the proportion of women with positive test results for each autoantibody in these 3 groups. Linear regression analysis showed significant correlation between anticardiolipin immunoglobulin G and beta(2)-glycoprotein I immunoglobulin G (R (2) = 0.544786, P =.0001) and anticardiolipin immunoglobulin M and beta(2)-glycoprotein I immunoglobulin M (R (2) = 0.525048, P =.0001). CONCLUSION: Both anticardiolipin and anti-beta(2)-glycoprotein I are associated with antiphospholipid syndrome. However, testing for anti-beta(2)-glycoprotein I does not identify additional patients with either recurrent spontaneous abortions or unexplained fetal deaths who initially have negative test responses for anticardiolipin. This is likely because of the strong correlation between the 2 autoantibodies. Our data do not support routine testing for anti-beta(2)-glycoprotein I in addition to testing for antiphospholipid antibodies in women with recurrent pregnancy loss and unexplained fetal death.

Abortion, Habitual↗
PubMed1999

Pregnancy complicated by the antiphospholipid syndrome: outcomes with intravenous immunoglobulin therapy.

OBJECTIVE: To assess maternal and fetal outcomes in 15 patients with antiphospholipid syndrome (19 pregnancies) treated with intravenous immunoglobulin (IV Ig) during pregnancy. METHODS: Monthly IV Ig therapy was initiated in the first or early second trimester of all pregnancies except two. Additional therapy consisted of low-dose aspirin and subcutaneous heparin. Six patients also received steroid therapy. Serial anticardiolipin IgG levels were measured in eight pregnancies. RESULTS: The live-birth rate was 84% (16 of 19 live births), and there were three pregnancy losses. There were no cases of fetal growth restriction (FGR). Preeclampsia and nonreassuring fetal status were each diagnosed in 25% of the pregnancies. Seventy-five percent of the infants were delivered at 34 weeks' gestation or later. Anticardiolipin IgG decreased throughout the course of therapy in seven pregnancies. Placental pathology was minimal. CONCLUSION: Pregnancy complications appear to be minimized with the use of IV Ig. Definitive recommendations regarding the use of IV Ig in pregnancy await the conclusion of randomized trials. If the combination of IV Ig, aspirin, and heparin significantly decreases the incidences of FGR and prematurity, it may be a cost-effective primary therapy for pregnancies complicated by the antiphospholipid syndrome.

Adult↗