IgA anti-ß2 glycoprotein I antibodies: Experience from a large center.

OBJECTIVE: IgG and IgM antibodies directed at ß2-glycoprotein I are included in the classification criteria for the antiphospholipid syndrome (APS) while the IgA antibodies against ß2-glycoprotein I (IgA aß2GPI) are not. Conflicting data about the significance of IgA aß2GPI and APS manifestation can be found and more studies are necessary in order to define the diagnostic value of IgA aß2GPI. In the present article, we investigated the possible role of IgA aß2GPI as marker of APS. METHODS: A cohort of 314 patients with APS and systemic autoimmune disease was investigated for the presence of IgA aß2GPI and its association with clinical manifestation of APS. RESULTS: Eighty-nine patients presented IgA aß2GPI, 68 cases associated with others antiphospholipid antibodies (aPL) and in 21 cases being the only aPL present. In primary APS IgA aß2GPI are highly coincidental with other aPL (92,2%) while most of the isolated IgA aß2GPI were present in the SLE group (16/21). No association between IgA aß2GPI and APS manifestations: thrombosis and pregnancy morbidity was found, while a positive association between IgA aß2GPI and the presence of anti-nDNA, anti-RNP, anti-Sm, anti-SSA, anti-SSB antibodies was encountered. CONCLUSION: Our study does not show association between IgA aß2GPI and APS manifestations and does not support the inclusion of IgA aß2GPI as a classification criteria for APS.

Actin polymerisation after FCγR stimulation of human fibroblasts is BCL10 independent.

B-cell lymphoma 10 (BCL10) is not essential for actin polymerisation after FcγR stimulation in human fibroblasts.

Case report: lupus nephritis with autoantibodies to complement alternative pathway proteins and C3 gene mutation.

BACKGROUND: Glomerulonephritis is one of the most severe complications of lupus, a systemic disease with multi-organ involvement, with tissue damage produced mainly by complement activation. As a result of this activation, patients with active lupus present hypocomplementemia during disease flares, but C3 and C4 levels are recovered between episodes. CASE PRESENTATION: We present a patient who suffered two lupus nephritis episodes in 5 years, achieving complete remission with treatment after both of them, but with C3 levels persistently below normal range. Genetic study revealed that the patient carried a mutation in heterozygosis in the C3 gene. Serial sera samples were analyzed, and autoantibodies to complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin) were found. Functional assays showed that these autoantibodies cause alternative pathway activation. CONCLUSION: This case is the first reported of a heterozygous C3 mutation associated with lupus nephritis and autoantibodies against complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin).These autoantibodies cause activation of this pathway and this fact could explain that the tissue damage is restricted to the kidney.

The effect of a triple therapy on maternal anti-Ro/SS-A levels associated to fetal cardiac manifestations.

OBJECTIVE: To evaluate the efficacy and safety of the combination of steroids, plasmapheresis and intravenous immunoglobulins (IVIG) on maternal anti Ro/SS-A antibody levels in cases of fetal cardiac involvement. MATERIAL AND METHODS: A series of three cases of positive anti-Ro/SS-A mothers with fetuses showing mild cardiac involvement were treated with a triple therapy composed of steroids, plasmapheresis and IVIG. Maternal antibody levels were measured several times before and after the application of each cycle of therapy. The effect of the treatment on fetal cardiac manifestations was also evaluated. RESULTS: Maternal anti-Ro/SS-A levels significantly decreased after each cycle of either plasmapheresis or IVIG therapy. The most significant decrease occurred after the first cycle. The natural evolution of the disease was stopped by this therapy in two of these cases, signs of cardiac inflammation decrease and none of the newborns needed neonatal pacemaker. CONCLUSIONS: A triple therapy combining plasmapheresis, IVIG and glucocorticoids may stop the natural evolution of the fetal cardiac affectation in positive anti-Ro/SS-A antibody patients. Further studies are needed in order to validate clinical applications of this treatment approach.

[Antipituitary antibodies in patients with suspected autoimmune hypophysitis]. / Anticuerpos antihipófisis en pacientes con sospecha de hipofisitis autoimmune.

INTRODUCTION: Definitive diagnosis of autoimmune hypophysitis (AH) is histological. However, a presumptive diagnosis can be made through clinical, biochemical and imaging data. OBJECTIVE: The objective of this study was to review the presence of antipituitary antibodies (APA) and antithyroid antibodies (ATA) in patients with suspected AH in order to determinate the utility of APA in the diagnosis of AH. MATERIAL AND METHODS: We studied 36 patients divided into seven groups according to the data suggesting AH (isolated corticotropin deficiency, other idiopathic pituitary deficiencies, idiopathic hyperprolactinemia, empty sella, sellar mass with thickened stalk, proven histological hypophysitis) or because of previous autoimmune endocrine diseases. Twenty-four controls without endocrinological disease were also included. In all subjects, APA were determined by immunofluorescence over primate pituitary gland and ATA by an agglutination technique. RESULTS: None of the controls and only 9 patients, all of them women, were APA-positive. Of the 9 APA-positive patients, 43% belonged to the group of patients with isolated ACTH deficiency. In 8 patients, APA were determined again during the follow-up; 6 remained APA-negative, but one patient became APA-positive and another became APA-negative. ATA were positive in 12 patients, 22.2% of whom were also APA-positive, and in one control. CONCLUSIONS: The prevalence of APA positivity among the study patients was low. These antibodies were found only in women, mostly with isolated corticotropin deficiency. APA and ATA coexisted in only 22% of the patients studied.

Anticuerpos antihipófisis en pacientes con sospecha de hipofisitis autoimmune / Antipituitary antibodies in patients with suspected autoimmune hypophysitis

Introducción El diagnóstico definitivo de la hipofisitis autoinmune es histológico; sin embargo, puede sospecharse en base a criterios clínicos, bioquímicos y radiológicos. Objetivo El objetivo de nuestro estudio fue revisar la presencia de anticuerpos antihipófisis (AAH) y anticuerpos antitiroideos en pacientes con sospecha de hipofisitis autoinmune por si la presencia de los primeros pudiera ayudar en el diagnóstico de la enfermedad. Material y métodos Estudiamos 36 pacientes divididos en 7 grupos por datos que hicieran sospechar una hipofisitis autoinmune (insuficiencia suprarrenal secundaria aislada, deficiencias hormonales sin causa justificada, hiperprolactinemia idiopática, silla turca vacía, masa selar con engrosamiento del tallo, confirmación histológica de hipofisitis) o por historia de autoinmunidad endocrina. Incluimos también 24 controles sin patología endocrina conocida. En todos se determinaron AAH mediante inmunofluorescencia indirecta sobre sustrato de glándula pituitaria de primate y anticuerpos antitiroideos mediante técnica de aglutinación. Resultados Los AAH fueron positivos en 9 pacientes, todos ellos mujeres, y en ningún control, perteneciendo el 43% de los pacientes con AAH positivos al grupo de pacientes con insuficiencia suprarrenal aislada. En 8 pacientes se determinaron de nuevo AAH durante el seguimiento, en 6 se mantuvieron negativos, en una se positivizaron y en otra se hicieron negativos. Los anticuerpos antitiroideos fueron positivos en 12 pacientes, de los cuales el 22,2% también tenían AAH positivos y en un control. Conclusiones La prevalencia de AAH fue baja, siendo todos los casos mujeres y en su mayoría con insuficiencia suprarrenal secundaria aislada. Solo en el 22% de los pacientes estudiados coexistieron AAH y anticuerpos antitiroideos (AU)

Introduction Definitive diagnosis of autoimmune hypophysitis (AH) is histological. However, a presumptive diagnosis can be made through clinical, biochemical and imaging data. Objective The objective of this study was to review the presence of antipituitary antibodies (APA) and antithyroid antibodies (ATA) in patients with suspected AH in order to determinate the utility of APA in the diagnosis of AH. Material and methods We studied 36 patients divided into seven groups according to the data suggesting AH (isolated corticotropin deficiency, other idiopathic pituitary deficiencies, idiopathic hyperprolactinemia, empty sella, sellar mass with thickened stalk, proven histological hypophysitis) or because of previous autoimmune endocrine diseases. Twenty-four controls without endocrinological disease were also included. In all subjects, APA were determined by immunofluorescence over primate pituitary gland and ATA by an agglutination technique. Results None of the controls and only 9 patients, all of them women, were APA-positive. Of the 9 APA-positive patients, 43% belonged to the group of patients with isolated ACTH deficiency. In 8 patients, APA were determined again during the follow-up; 6 remained APA-negative, but one patient became APA-positive and another became APA-negative. ATA were positive in 12 patients, 22.2% of whom were also APA-positive, and in one control. Conclusions The prevalence of APA positivity among the study patients was low. These antibodies were found only in women, mostly with isolated corticotropin deficiency. APA and ATA coexisted in only 22% of the patients studied (AU)

Recurrence of bile salt export pump deficiency after liver transplantation.

Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.

The proteasome is a major autoantigen in multiple sclerosis.

Multiple sclerosis seems to be an autoimmune disease of unknown aetiology affecting the white matter of the CNS. It is generally accepted that the autoimmune response is directed against specific components of myelin. We show here that proteasome, a ubiquitous protease complex composed of 14 different subunits, is a target for autoantibodies (IgG and IgM classes) present in the serum (66%, 73 out of 110) and in the CSF (61%, 16 out of 26) of patients with multiple sclerosis. Using recombinant proteasomal subunits we demonstrate the presence of specific autoantibodies against subunits C2, C8, C9 and C5 in multiple sclerosis patients. Recombinant C2 constructs allow us to localize an immunodominant autoepitope recognized by the sera of multiple sclerosis patients within the C-terminal of C2 proteasomal subunit (251-DEPAEKADEPMEH-263). In addition, two constructs of the recombinant proteasomal subunits C2 and C8 were also used to study the proliferation of peripheral blood mononuclear cells from multiple sclerosis patients; 12 out of 30 (40%) multiple sclerosis patients show positive proliferation with one or both of these recombinant subunits. The high prevalence of anti-proteasome autoantibodies in multiple sclerosis sera compared with sera from patients with other chronic inflammatory conditions: systemic lupus erythematosus (35%, 35 out of 100), primary Sjogren's syndrome (16%, 5 out of 31), vasculitis (0 out of 20), sarcoidosis (7%, 1 out of 13) and Behcet's disease (19%, 4 out of 21) suggest that humoral autoreactivity to proteasome could be a useful test in multiple sclerosis patients that may be of help in the diagnosis and/or progression of this chronic inflammatory disease. Finally, these results suggest that some global abnormality in B and/or T cell function is also involved in the chronic inflammatory response observed in multiple sclerosis patients, as it is frequently observed in other human organ-specific autoimmune diseases.