RESUMO
We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-beta2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-beta2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and anti-beta2GPI ELISA was more specific than aCL in both populations.
Assuntos
Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/imunologia , Glicoproteínas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/imunologia , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/epidemiologia , Criança , Pré-Escolar , Colômbia/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Espanha/epidemiologia , Trombose/diagnóstico , Trombose/epidemiologia , Trombose/imunologia , beta 2-Glicoproteína IRESUMO
The aim of this study was to investigate the interaction of antiphospholipid antibodies (aPL) from two different populations (patients with autoimmune or infectious disorders) with cardiolipin (CL) arranged in a defined bilayer. beta2-Glycoprotein I (beta2GPI), an apolipoprotein that plays a critical role in the aPL binding to phospholipids, was quantified by dot blot in purified IgG-aPL samples, further classified according to apparent avidity to CL. In solid-phase assays, beta2GPI increased, preferentially, the binding of low-avidity autoimmune aPL to CL but inhibited the binding of low-avidity syphilitic aPL. In the absence of beta2GPI, both autoimmune and infectious aPL induced the leakage of the entrapped fluorescent probe, carboxyfluorescein (CF), from small unilamellar vesicles containing CL. aPL-induced probe leakage was protein concentration-dependent and characterized by a lag-phase onset of 100-120 min. beta2GPI increased the leakage rate induced by low-avidity autoimmune aPL only and inhibited the leakage induced by all syphilitic aPL. The following conclusions were provided: (1) in the absence of beta2GPI, autoimmune and infectious aPL bind to CL in a bilayer, inducing liposome leakage; (2) the leakage mechanism induced by aPL is suggested to be intravesicular; (3) beta2GPI requirement for phospholipid binding in both solid and fluid phase is associated to aPL avidity; (4) CL alone or the CL-beta2GPI complex are the most likely epitopes for autoimmune aPL; (5) aPL from syphilis patients can only form the CL-aPL complex, supporting that beta2GPI is not (part of) the target epitope.
Assuntos
Anticorpos Antifosfolipídeos/imunologia , Afinidade de Anticorpos , Cardiolipinas/imunologia , Glicoproteínas/imunologia , Anticorpos Anticardiolipina/sangue , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Doenças Autoimunes/sangue , Cardiolipinas/análise , Epitopos/análise , Fluoresceínas , Corantes Fluorescentes , Glicoproteínas/análise , Humanos , Imunoglobulina G/análise , Lipossomos/química , Permeabilidade , Sífilis/sangue , beta 2-Glicoproteína IRESUMO
Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, AIDS) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/imunologia , Anticorpos Antifosfolipídeos/isolamento & purificação , HumanosRESUMO
Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, AIDS) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies
Assuntos
Humanos , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/fisiopatologia , Anticorpos Antifosfolipídeos/isolamento & purificação , Síndrome Antifosfolipídica/imunologiaRESUMO
OBJECTIVE: To investigate the prevalence of anticardiolipin antibodies (aCL) and isotype distribution and their clinical associations with the features of the antiphospholipid syndrome (APS) in 3 different ethnic groups of patients with systemic lupus erythematosus (SLE). METHODS: The study population consisted of 152 African-American, 136 Afro-Caribbean (Jamaican), and 163 Hispanic (Colombian) unselected patients with SLE. Serum samples were studied for the prevalence of aCL and isotype distribution. All aCL measurements were performed in the same laboratory by ELISA. RESULTS: Positive results for 1 of the 3 aCL isotypes were found in 42 African-Americans (28%), 28 Afro-Caribbeans (21%), and 43 Hispanics (26%). IgG aCL was the dominant isotype in Hispanic and African-American patients, while IgA was the dominant isotype in Afro-Caribbeans. Of note, IgA aCL was found in all Afro-Caribbean patients who were aCL positive, while only 3 patients in this group had IgG aCL and 2 had IgM aCL. Clinical features of the APS were found to correlate better in Hispanics than in African-Americans and Afro-Caribbean patients with aCL isotypes. CONCLUSION: Our data suggest the existence of ethnic differences in the prevalence and isotype distribution of aCL as well as in their clinical relevance in patients with SLE. Further studies of the role of genetic and/or environmental factors in the observed differences are required.