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L R Sammaritano

Publications and source records attributed to L R Sammaritano.

At least 19 recordsLinked to original sources
PubMed2001

Update on the management of the pregnant patient with antiphospholipid antibody.

Management of the pregnant patient with antiphospholipid antibody (aPL) is reviewed, with emphasis on recent randomized controlled clinical trials. These support the use of subcutaneous heparin and low dose aspirin, current standard therapy for women with aPL and a history of fetal loss. Prednisone is rarely used due to high risk of maternal and fetal morbidity. Intravenous immunoglobulin may represent an important additional therapy for women who fail aspirin and heparin. Patients with a history of thrombosis require full, therapeutic anticoagulation during pregnancy. Recommendations are less clear for newly described antibodies to phospholipid-binding protein, for low titer antibodies, and for infertility treatment in the setting of aPL.

Anticoagulants↗
PubMed2001

Effect of cardiolipin oxidation on solid-phase immunoassay for antiphospholipid antibodies.

Diagnostic assays for antiphospholipid antibodies are routinely performed on microtitre plates coated with cardiolipin. Here we show that contact between cardiolipin and NUNC-Immuno plates leads to extensive oxidation, generating a series of peroxy-cardiolipins which were identified by electrospray ionization mass spectrometry. To investigate the impact of oxidation on the antibody assay. cardiolipin was resolved into 12 molecular species, including oxidized species and non-oxidized species with different degrees of unsaturation. All 12 species reacted under anaerobic conditions with serum from patients with primary antiphospholipid syndrome. Immune reactivity was similar for tetralinoleoyl-cardiolipin, trilinoleoyl-oleoyl-cardiolipin, and peroxycardiolipins, but somewhat lower for tristearoyl-oleoyl-cardiolipin. Oxidative treatment of cardiolipin with air, cytochrome c, or Cu2+/tert-butylhydroperoxide, either before or during the assay, did not enhance immune reactivity. Similar results were obtained with a monoclonal IgM from lupus-prone mice, that binds cardiolipin in the absence of protein cofactors. We conclude that the solid-phase assay for antiphospholipid antibodies can be supported by various oxidized and non-oxididized molecular species of cardiolipin.

Adult↗
PubMed2000

Validation of the Sapporo criteria for antiphospholipid syndrome.

OBJECTIVE: To test the Sapporo criteria for the classification of the antiphospholipid syndrome (APS). METHODS: We classified 243 consecutive patients who had clinical diagnoses of primary APS (n = 49), secondary APS (n = 26), systemic lupus erythematosus (SLE) without clinical APS (n = 131), and lupus-like disease without clinical APS (n = 37). RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value were 0.71, 0.98, 0.95, and 0.88, respectively. False-negative findings were the result of patients being classified on the basis of minor criteria that were not included in the Sapporo criteria, such as livedo reticularis, thrombocytopenia, low-titer IgG or IgM anticardiolipin antibody, IgA anticardiolipin antibody, and anti-beta2-glycoprotein I antibody. Some patients with false-negative results were true seronegative cases. CONCLUSION: The Sapporo criteria for APS compare favorably with the American College of Rheumatology criteria for SLE and are usable for clinical studies.

Adult↗
PubMed1999

A role for the polymorphism at position 247 of the beta2-glycoprotein I gene in the generation of anti-beta2-glycoprotein I antibodies in the antiphospholipid syndrome.

OBJECTIVE: To determine the frequencies at which either a valine or leucine occurs at position 247 in the beta2-glycoprotein I (beta2GPI) gene of normal individuals of the Caucasian, African American, and Asian ethnic groups and to compare these data with those in patients with the antiphospholipid syndrome (APS), with and without anti-beta2GPI antibodies. METHODS: The DNA segment containing the position-247 polymorphism was amplified by seminested polymerase chain reaction, and the polymorphism was detected by restriction endonuclease digestion. DNA samples from 370 healthy controls of different racial backgrounds were analyzed, and the results were compared with those from 149 APS patients (66 primary; 83 secondary). Allele and genotype frequencies were compared using Fisher's exact test. When significant differences were detected, pairwise comparisons were made using Fisher's exact test with a Bonferroni adjustment. RESULTS: Allele and genotype expression was significantly different (P < 0.0001 for both) among the 3 races, with the V allele and the VV genotype occurring most often among Caucasians, less among African Americans, and least among Asians. Conversely, the V allele and the VV genotype were found more frequently among Asian APS patients than among controls (P = 0.0028 and P = 0.0023, respectively). No significant differences in allele or genotype frequencies were seen in comparisons of the Caucasian or the African American patients with appropriate controls. The differences in allele and genotype frequencies seen in the Asian APS patients were restricted to the anti-beta2GPI-positive patients (P = 0.0018 and P = 0.0005, respectively). CONCLUSION: In Asian patients with APS, expression of a V at position 247, especially in the homozygous state, is significantly associated with the presence of anti-beta2GPI antibodies and, therefore, can be viewed as a major risk factor in this ethnic group (odds ratio 9.19 and 16.33, respectively).

Alleles↗
PubMed1998

Placental pathology in systemic lupus erythematosus: a prospective study.

OBJECTIVES: Systemic lupus erythematosus and antiphospholipid antibody, often identified in patients with systemic lupus erythematosus, are associated with poor pregnancy outcome. This study distinguishes between the effect of each of these factors on gestational outcome and placental pathologic conditions in pregnant patients with systemic lupus erythematosus. STUDY DESIGN: Thirty-seven pregnancies and 40 placentas from 33 women with systemic lupus erythematosus were studied prospectively. RESULTS: Systemic lupus erythematosus alone, but not systemic lupus erythematosus activity, was associated with increased spontaneous abortions, preterm gestations, and fetal growth restriction. Placental correlates were ischemic-hypoxic change, decidual vasculopathy, decidual and fetal thrombi, chronic villitis, and decreased placental weight. Extensive infarction and fetal death were important antiphospholipid antibody-related findings. CONCLUSIONS: Decidual vasculopathy/coagulopathy appears to mediate the antiphospholipid antibody-related and much of the systemic lupus erythematosus-related deleterious effect on the placenta and gestational outcome. The presence of antiphospholipid antibody largely, but not invariably, predicts fetal death. Antiphospholipid antibody-independent chronic villitis may represent a second mechanism of systemic lupus erythematosus-related change.

Adult↗
PubMed1998

Corticosteroids during pregnancy.

In pregnancy, pharmacokinetics of corticosteroids changes. Systemic corticosteroids are not teratogenic. Pregnant women receiving corticosteroid therapy suffer the same side effects and benefits as do treated women who are not pregnant. Clinical experience suggests no abnormalities of children of mothers treated with usual doses of prednisone and methylprednisolone throughout pregnancy, but premature rupture of amniotic membranes and low birthweight babies may occur. Betamethasone and dexamethasone are used to treat the fetus. The effect on the fetus of bolus doses of methylprednisolone is unknown. Very little corticosteroid ingested by the mother enters her breast milk. Corticosteroid therapy in pregnancy is appropriate to control clinically active maternal illness; to treat an in utero infant suffering from neonatal lupus-associated carditis; in stress doses (in corticosteroid-treated patients) for labor and delivery: and, pre-delivery, to induce fetal lung maturation.

Adrenal Cortex Hormones↗
PubMed1997

Anticardiolipin IgG subclasses: association of IgG2 with arterial and/or venous thrombosis.

OBJECTIVE: To determine whether the presence of anticardiolipin antibodies (aCL) of a specific IgG subclass is associated with clinical complications of the antiphospholipid antibody syndrome (APS) and whether polymorphisms of Fc receptors for IgG (FcgammaR) with differential binding preferences contribute to an increased risk of thrombotic complications. METHODS: In 60 patients with IgG aCL, we assessed clinical complications of the APS, measured the level of antibody activity, and determined the IgG subclass distribution of aCL by a modified enzyme-linked immunosorbent assay (ELISA) with murine anti-human IgG subclass monoclonal antibodies. Selective IgG subclass adsorption studies were performed to determine the relative contribution of specific IgG subclasses to overall aCL activity. Fcgamma receptor IIA (FcgammaRIIA) genotypes of aCL patients with thrombosis and of non-systemic lupus erythematosus controls were determined by polymerase chain reaction amplification of genomic DNA and allele-specific probes. RESULTS: IgG2 aCL, detected in 75% of the patients, was the major subclass of aCL. Selective adsorption studies demonstrated that IgG2, in contrast to IgG1, was the predominant subclass responsible for aCL reactivity. IgG2 aCL was the only subclass associated with clinical complications, specifically, arterial and/or venous thrombosis (P < 0.04). The presence of FcgammaRIIA-H131, a receptor expressed on platelets, monocytes, and endothelial cells and the only human FcgammaR which efficiently recognizes IgG2, was associated with thrombosis in aCL patients. Among 45 high-titer (>40 GPL [IgG phospholipid] units) aCL patients with thrombosis, 40% were homozygous for FcgammaRIIA-H131, compared with 25% of disease-free controls (P = 0.042). CONCLUSION: While all 4 IgG subclasses are found in autoimmune aCL, only the presence of IgG2 is significantly associated with thrombotic complications. Reactivity in aCL ELISA is largely due to the presence of IgG2 in high-titer patients. The presence of IgG2 aCL, particularly in association with FcgammaRIIA-H131, may be a useful clinical predictor of increased thrombotic risk in patients with autoimmune IgG aCL. Allelic variants of FcgammaRIIA with distinct capacities to interact with IgG subclasses provide a mechanism for genetic susceptibility to an autoantibody-induced prothrombotic state.

Alleles↗
PubMed1996

Significance of aPL IgG subclasses.

Human immunoglobulin G (IgG) is comprised of four subclasses with distinct structural and biologic properties. Patients with autoimmune disease, in general, show an overall increase in serum IgG as well as skewing in subclass distribution for particular autoantibodies. Antinuclear antibodies and anti-double stranded DNA antibodies, for example, are primarily IgG1 and IgG3. In contrast, anticardiolipin antibodies show a skewing towards presence of IgG2 presence is associated with arterial and venous thrombotic complications. Selective absorption of IgG2 from high titer sera abrogates aCL ELISA binding. Pathogenicity of aCL may be related to IgG2 in an important way. The precise mechanism of action and nature of the inducing stimulus are not yet clear.

Antibodies, Anticardiolipin↗
PubMed1996

Antiphospholipid antibodies activate vascular endothelial cells.

Antiphospholipid antibodies (aPL) are associated with a syndrome of arterial and venous thrombosis and recurrent fetal loss. We have shown that IgG purified from patients with aPL activate vascular endothelial cells (EC), converting the steady-state, non-thrombotic endothelial surface to a pro-thrombotic state. The aPL-activated EC are characterized by the expression of leukocyte adhesion molecules, including ICAM-1, VCAM, and E-selectin. EC activation is dependent upon the presence of beta 2-GP-I, a cofactor necessary for anticardiolipin reactivity. In addition, EC activation is not attributable to endotoxin contamination, Fc receptor interactions, or immune complexes, but rather is the result of the specific anticardiolipin reactivity of the IgG. Endothelial activation by aPL may be an important mechanism by which these antibodies cause a hypercoagulable state.

Antibodies, Antiphospholipid↗
PubMed1995

Activation of cultured vascular endothelial cells by antiphospholipid antibodies.

Circulating antiphospholipid antibodies (aPL) are associated with a syndrome of thrombosis, recurrent fetal loss, and thrombocytopenia. We have demonstrated the activation of cultured human umbilical vein endothelial cells (HUVEC) by IgG from patients with anticardiolipin antibodies (aCL). Incubation of HUVEC for 4 h with purified IgG (100 micrograms/ml) from patients with high-titer aCL induced a 2.3-fold increase in monocyte adhesion over that seen in HUVEC incubated with IgG's from normal subjects. The effect of aCL was not attributable to LPS contamination, Fc receptors, or immune complexes. Monocyte adhesion was not induced when the aCL were added in serum-free media but was restored by the addition of purified beta 2GP1, previously described as a necessary cofactor for aCL reactivity. Purified rabbit polyclonal IgG raised against beta 2GP1 also induced monocyte adhesion when incubated with HUVEC. Preadsorption of patient serum with cardiolipin reduced monocyte adhesion by 60%. Immunofluorescent microscopy demonstrated that endothelial cells incubated with patient IgG expressed cell adhesion molecules, including E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. These data support the hypothesis that aPL activate vascular endothelial cells, thereby leading to a pro-thrombotic state.

Antibodies, Antiphospholipid↗
PubMed1995

Specificities and characteristics of beta 2 glycoprotein I-induced antiphospholipid antibodies.

Autoimmune antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and recurrent fetal death. These antibodies are thought to be directed against an epitope formed by phospholipids complexed with beta 2 glycoprotein I (beta 2GPI), a plasma protein with affinity for phospholipids. By immunizing mice and rabbits with heterologous beta 2GPI, we produced antibodies that bind strongly to acidic phospholipids in addition to binding to beta 2GPI. To evaluate the specificities of these antibodies, we passed the serum of a rabbit immunized with beta 2GPI through a cardiolipin (CL) affinity column and studied the bound and fall-through antibodies for binding to CL and beta 2GPI by ELISA. The results demonstrated the presence of two populations of antibodies, one with specificity for beta 2GPI alone without binding to phospholipids and the other with specificities for both CL and beta 2GPI. These dual-specificity antibodies are similar to the antiphospholipid antibodies present in autoimmune diseases because they bind to other acidic phospholipids in addition to CL and because their binding to phospholipids is enhanced by beta 2GPI and blocked by placental anticoagulant protein I (annexin V).

Animals↗
PubMed1994

Characteristics of human immunodeficiency virus and chlorpromazine induced antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to phospholipid.

OBJECTIVE: To investigate the nature of the target epitope for human immunodeficiency virus (HIV) and chlorpromazine (CPZ) induced antiphospholipid antibodies (aPL) by evaluating the effect of the aPL cofactor (beta 2 glycoprotein I) on phospholipid binding and to compare this with known binding patterns of infection induced and autoimmune aPL. METHODS: aPL positive sera from 17 patients with HIV and 16 patients with schizophrenia treated with CPZ were tested and compared with aPL positive sera from 20 patients with syphilis and 35 with autoimmune disease. Both the sera and either IgG fractions prepared by affinity chromatography or IgM fractions prepared by euglobulin precipitation and gel filtration were tested for binding to cardiolipin (CL) in ELISA in the presence and absence of purified human beta 2 glycoprotein I (beta 2-GPI). Competition studies evaluated biotinylated CPZ IgM aPL binding and the effect on this of added aPL, placental anticoagulant protein I--a phospholipid binding protein that inhibits autoimmune aPL--and CL vesicles. RESULTS: HIV IgG aPL binding to CL was inhibited by beta 2-GPI (51-53%), like syphilis IgG aPL and in contrast to autoimmune IgG aPL. CPZ IgM aPL, like autoimmune IgM aPL, bound more efficiently in the presence of beta 2-GPI, with binding increases of 31-149%. Binding of biotinylated CPZ IgM aPL to CL was competitively inhibited by autoimmune IgG aPL (47%) and CPZ aPL (92%) but not by HIV IgG aPL or normal IgG. Placental anticoagulant protein I and CL vesicles completely prevented binding of CPZ IgM aPL to CL (100 and 96% inhibition, respectively). CONCLUSIONS: Findings indicate that CPZ aPL resembles the autoimmune aPL, whereas aPL found in HIV infection do not appear to be of autoimmune type.

Antibodies, Antiphospholipid↗
PubMed1993

Do patients with antiphospholipid syndrome have autoantibodies to beta 2-glycoprotein I?

High positive anticardiolipin antibody tests have been associated with recurrent thrombosis and pregnancy loss. Although these antibodies were believed to bind negatively charged phospholipids, recent reports have suggested that a serum protein, beta 2-glycoprotein I (beta 2-GPI), may be the true antigen for these antibodies. To resolve this issue, we compared binding of 75 anticardiolipin-positive and 71 anticardiolipin-negative serum samples from patients with rheumatic diseases to beta 2-GPI by using an enzyme-linked immunosorbent assay (ELISA). Serum samples from 30 healthy blood donors and 10 laboratory personnel were used as normal controls. We found no difference in binding between the three groups of serum samples. In addition, when binding to beta 2-GPI coated plates was compared with binding to ELISA plates without beta 2-GPI (blank), no difference was observed. Finally, binding of anticardiolipin-positive serum samples to plates coated with cardiolipin-beta 2-GPI mixture varied directly with the cardiolipin concentrations. Based on these findings, we conclude that anticardiolipin-positive serum samples do not bind beta 2-GPI.

Antiphospholipid Syndrome↗