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M D Lockshin

Publications and source records attributed to M D Lockshin.

At least 19 recordsLinked to original sources
PubMed1992

Serologic studies of monozygotic twins with systemic lupus erythematosus.

OBJECTIVE: The goal of these studies was to assess the role of genetic factors and disease expression in the pattern and titer of autoantibodies to several RNA protein antigens in patients with systemic lupus erythematosus (SLE) by studying identical twins concordant and discordant for disease expression. METHODS: Autoantibodies to Ro/SS-A, La/SS-B, U1 RNP, and Sm were measured by quantitative enzyme-linked immunosorbent assay using affinity-purified antigens. RESULTS: Detailed serologic studies were performed in 7 pairs of identical twins, 3 of whom were concordant and 4 of whom were discordant for disease expression. Autoantibody titers were higher in affected than in unaffected twins from discordant pairs, but in 3 of 4 pairs, the profile of anti-RNA proteins (e.g., Ro/SS-A, La/SS-B, U1 RNP, and Sm) was virtually identical. In the SLE pairs concordant for disease expression, the autoantibody titers were very similar, as were the anti-RNA protein profiles. When the identical twins were matched by sex, race, and age to pairs of nontwin SLE patients, the 6 white twins shared an average of 2.5 (+/- 1.05 SD) anti-RNA proteins, while the control SLE pairs shared only 0.33 (+/- 0.82), P less than 0.01 (t = 4.0, P less than 0.01). In addition, in the white SLE twins, all had elevated levels of anti-U1 RNP while in white nontwin SLE patients, the frequency of anti-U1 RNP was 30%. CONCLUSION: These data point to a dominant role for genetic factors in the determination of specific autoantibody profiles.

Antigen-Antibody Reactions↗
PubMed1992

Phospholipid binding of antiphospholipid antibodies and placental anticoagulant protein.

We evaluated the interaction of antiphospholipid antibodies (aPL) with placental anticoagulant protein I (PAP I), a calcium-dependent phospholipid binding protein which may act as a natural anticoagulant. Clotting assays showed additive prolongation of clotting times with aPL and PAP I. ELISA and vesicle phospholipid binding studies showed PAP I inhibition of aPL binding to phospholipid but no inhibition of PAP I-phospholipid binding by aPL. aPL and PAP I interact additively in anticoagulant activity in in vitro clotting systems and compete for phospholipid in ELISA system. These data support the hypotheses that aPL and PAP I may recognize similar phospholipid epitopes and that in vivo interaction may occur.

Annexins↗
PubMed1992

Antiphospholipid antibodies differ in aPL cofactor requirement.

Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta 2-glycoprotein I (beta 2GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified beta 2GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to beta 2GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if beta 2GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications.

Antibodies, Antiphospholipid↗
PubMed1991

Antiphospholipid antibody and antiphospholipid antibody syndrome.

New details have been added to the description of the antiphospholipid antibody syndrome. These include quantitation of risk of stroke; delineation of an associated acute occlusive vasculopathy syndrome, including its pathology; increased awareness of the association of adrenal insufficiency with antiphospholipid antibody; new demonstration of placental pathology in cases of fetal death; and new details on the persistence or transience of antibody in patients with systemic lupus erythematosus. There are several animal models for the antiphospholipid antibody syndrome. Assay standardization and reproducibility issues, more for the lupus anticoagulant than for the enzyme-linked immunosorbent assay for antiphospholipid antibody, remain as important barriers to progress. Antibody characteristics of activity, isotype, and subclass must be considered in assay interpretation; antigen characteristics of fatty acid chain and lipid phase are also important variables. Other circulating proteins may have clinical importance. Several laboratories have commented that antiphospholipid antibody interferes with protein C. A cofactor, apolipoprotein H, enhances binding of some antiphospholipid IgG antibodies. Other phospholipid-binding proteins are known. Isolation, purification, and perhaps cloning of many of these factors should lead to a better understanding of the pathogenesis of the syndrome.

Annexins↗
PubMed1991

Pregnancy and aPL.

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Abortion, Spontaneous↗
PubMed1991

Occlusive vasculopathy in systemic lupus erythematosus. Association with anticardiolipin antibody.

Patients with systemic lupus erythematosus and with antiphospholipid antibody are subject to sudden occlusion of multiple blood vessels. We describe two patients with systemic lupus erythematosus with acute, catastrophic, widespread non-inflammatory visceral vascular occlusions associated with high-titer antiphospholipid antibody. The histopathologic features clearly distinguished these patients from classic systemic lupus erythematosus vasculitis. We further suggest that, based on a probable pathogenesis related to the presence of antiphospholipid antibody, and based on the non-inflammatory vascular occlusion, steroids and other immunosuppressive medications are of limited value. Plasmapheresis along with anticoagulant therapy should be considered.

Adult↗
PubMed1990

Characteristics of high-titer IgG antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death.

Although high-titer IgG antiphospholipid antibody (aPL) is a predictor of mid-pregnancy fetal death in women with systemic lupus erythematosus (SLE), some SLE patients with high-titer aPL carry pregnancies normally, and to term. To determine potential antibody differences between IgG aPL-positive women with and without fetal death, we studied aPL isotype, subclass, anticoagulant activity, phospholipid specificity, and antibody avidity in selected sera from pregnant SLE patients with high-titer IgG aPL. For controls, we selected sera from pregnant SLE patients who had negative results on tests for IgG aPL (with and without fetal loss). None of the specified antibody characteristics distinguished between the aPL-positive patient groups, nor were other specificities defined in IgG aPL-negative sera from women with fetal death. Although high-titer aPL is a good predictor of fetal death, currently known characteristics, other than a high titer of aPL, do not identify which women will experience this complication.

Antibody Specificity↗
PubMed1990

Fatty acid chain is a critical epitope for antiphospholipid antibody.

To explore the role of phospholipid fatty acids in binding of antiphospholipid antibody (aPL) in ELISA, we tested aPL binding to phospholipids containing fatty acids of varying chain length and degree of saturation using direct ELISA and inhibition methods. Polyclonal IgG and IgM human aPL's bind to C18:1 phosphatidylglycerol (PG) better than to C18:0 PG or C18:2 PG. Binding is greater to C18 than to C14:0 or C16:0 PGs; aPL's do not bind to C12:0 PG. aPL binding is not inhibited by C18:1 diacylglycerol, glycerol-3-phosphate, myoinositol, or myoinositol phosphate. The fatty acid chains are critical determinants for antigen recognition and, by projection, biological activity of aPL.

Autoantibodies↗
PubMed1990

Lysophosphatidylethanolamine is the antigen to which apparent antibody to phosphatidylethanolamine binds.

Because binding of antiphospholipid antibody (aPL) to phosphatidylethanolamine (PE) is central to the definition of the antigenic epitope targeted by aPLs, we examined the binding of aPL-positive SLE sera to PE under various conditions. No serum bound to PE uncontaminated with lysophosphatidylethanolamine (1PE), but many aPL-positive sera bound to 1PE-contaminated PE and to 1PE coated onto an ELISA plate. Absorption studies indicated partial cross-reactivity between PE containing 1PE and cardiolipin. We conclude that clinical aPLs do not bind to PE. Prior reports to the contrary most likely represent binding of aPL to PE's degradation product, 1PE.

Autoantibodies↗
PubMed1990

Antiphospholipid antibody syndrome: immunologic and clinical aspects.

Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss, and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. A positive antiphospholipid antibody test is defined by enzyme-linked immunosorbent assay (ELISA) (antiphospholipid antibody itself) or by coagulation assay (lupus anticoagulant). These are similar but not identical antibodies. The test for syphilis is less closely related to the preceding two and is less regularly associated with clinical complications. The mechanism of action of either antiphospholipid antibody or lupus anticoagulant is as yet unknown. SLE-induced but not infection-induced antiphospholipid antibody has immunoglobulin G2 (IgG2) and IgG4 predominance. It recognizes all negatively charged phospholipids, but various physical characteristics of the phospholipids alter the recognition patterns. Treatment for the antiphospholipid antibody syndrome has not been clearly defined. Anticoagulation with aspirin, heparin, or warfarin is currently favored. A role for corticosteroid remains to be demonstrated.

Antibodies↗
PubMed1990

Characteristics of IgG antiphospholipid antibodies in patients with systemic lupus erythematosus and syphilis.

To evaluate the similarities and differences of antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) and syphilis, we studied 20 SLE and 16 syphilis high titer IgG aPL sera for antibody isotype, avidity, phospholipid specificity, light chain and IgG subclass. Syphilis aPL had lower avidity, with kappa light chain and IgG1 and IgG3 predominance, in contrast to higher avidity, with lambda light chain and IgG2 and IgG4 predominance in SLE aPL. Phospholipid specificities were similar. SLE and syphilis aPL both recognize phospholipid epitopes but differ in important antibody characteristics.

Autoantibodies↗
PubMed1990

Pregnancy associated with systemic lupus erythematosus.

Lupus pregnancies may be complicated by difficulties in the diagnosis of flare, by complications related to aPL antibody, complications related to neonatal lupus, and by a high frequency of preeclampsia. Lupus pregnancies are often difficult to manage, but most complications can be anticipated and, with care, successfully managed.

Female↗