Henrique Luiz Staub

Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis.

Most patients with lupus anticoagulant (LA) activity have coincident antibodies to a group of negatively charged phospholipids, and its is suggested that LA and anticardiolipin tests detect antibodies with overlapping specificities. Some discordance between the two assays has been described, however. One patient presenting with severe thrombotic disease (recurrent deep vein thrombosis, pulmonary embolism, inferior venocaval obstruction, myocardial infarction, and digital gangrene) showed strong LA activity in February 1987. An enzyme linked immunosorbent assay (ELISA) showed no binding to the negatively charged phospholipids cardiolipin, phosphatidylserine, and phosphatidic acid, but binding to zwitterionic phosphatidylethanolamine (PE) was demonstrated. Inhibition studies and affinity purification confirmed this finding. Interestingly, the serum did not bind to the kaolin cephalin clotting time reagent when used as antigen in an ELISA. The pathogenic significance of anti-PE antibodies and their relation to LA remains to be clarified. Further studies of the occurrence of anti-PE antibodies in patients with LA activity who have negative anticardiolipin tests are suggested.

Antibodies to the atherosclerotic plaque components beta2-glycoprotein I and heat-shock proteins as risk factors for acute cerebral ischemia

One third of cases of cerebral ischemia have no clear etiology. A humoral response to the atherosclerotic plaques components beta2-glycoprotein l (beta2-gpl) and heat-shock proteins (Hsp) might be involved in the pathogenesis of stroke. This case-control study includes a complete profile of anti-beta2-gpl antibodies and testing of IgG antibodies to the 60/65 kilodaltons (kDa) Hsp in stroke patients. Ninety-three patients with acute ischemic stroke and 93 controls were evaluated for age, sex, race, hypertension, smoking, previous cardiopathy, diabetes mellitus, hypercholesterolemia and previous history of cerebral ischemia. lgG/lgM/lgA anticardiolipin (aCL) and anti-beta2-gpl antibodies, as well as lgG antibodies to human 60 kDa Hsp and to Mycobacterium bovis 65 kDa Hsp, were detected by immunoassay. Adjusted odds ratios (OR) were calculated by logistic regression. The adjusted OR for IgA anti-beta2-gpl antibodies was 4.6 (90%Cl 1.5 to 14.3; p = 0.025). The non-adjusted OR for IgG antibodies to Hsp 60 was 26.1. The adjusted OR for IgG antibodies to Hsp 65 was 3.2 (90%Cl 1.2 to 8.3; p = 0.044). The adjusted OR for lgG to any Hsp (60 or 65) was 4.8 (90%Cl 1.9 to 12.1; p = 0.006). This study demonstrates that elevated IgA anti-beta2-gpl and lgG anti-Hsp 60/65 antibodies are associated with increased risk of ischemic stroke. The association occurred independently of other risk factors. This humoral response might link autoimmunity, thrombophilia and atherosclerosis in stroke patients.

Anticorpos contra beta2-glicoproteína I como fatores de risco para infarto agudo do miocárdio

OBJECTIVE: To determine whether high levels of antibodies against the phospholipid beta2-glycoprotein I (beta2-gpI) cofactor are associated with an increase in the risk of acute myocardial infarction. METHODS: The study comprised 82 patients with acute myocardial infarction and 82 controls, who were assessed in regard to age, sex, race, hypertension, smoking, previous heart disease, history of diabetes mellitus, and hypercholesterolemia. The following antibodies were detected using immunoassay: anticardiolipin and anti-beta2-gpI IgA, IgG, and IgM. Adjusted odds ratios (OR) for risk factors were obtained through logistic regression. RESULTS: The mean ages of the cases and controls were, respectively, 57.7 and 51.1 years (P=0.003). Men (P=0.005) and the white race predominated in both groups (P=0.798). Of the risk factors, a history of diabetes (OR=5.3; 95% CI: 1.9 to 14.9; P=0.001) and previous heart disease (OR=4.7; 95% CI: 2.0 to 10.7; P<0.001) were the most consistent associations with myocardial infarction. The frequency of anticardiolipin IgG, IgM, and IgA antibodies did not differ between cases and controls (P=1.000). Anti-beta2-gpI IgA antibodies were more frequent in cases than in controls (P=0.054). The adjusted OR for anti-beta2-gpI IgA antibodies was 3.4 (95% CI: 1.3 to 9.1; P=0.015). CONCLUSION: Anti-beta2-gpI IgA antibodies, but not anticardiolipin antibodies, seemed to behave as independent risk factors for myocardial infarction, which may represent a link between autoimmunity and atherosclerosis in patients with acute myocardial infarction.

Anti-phosphatidylethanolamine antibody, thromboembolic events and the antiphospholipid syndrome

The antiphospholipid syndrome (APS) is an acquired disorder characterized by arterial and/or venous thrombosis and pregnancy morbidity. In solid assays, sera from patients with APS usually react to negatively charged phospholipids (PL) and PL cofactors such as β2-glycoprotein I (β2GPI). Binding to neutral PL such as phosphatidylethanolamine (PE) is less common. PE is one of the main lipid components of the biological membranes, being mostly located in the inner leaflet. In 1989 we reported the first case of primary APS whereby a LA was accompanied not by an anticardiolipin antibody (aCL), but by an antibody to PE (aPE). In this review, we update the literature concerning the presence of aPE in patients with thromboembolic events and obstetric morbidity. We also discuss aPE as the sole antibody detected in many of these clinical circumstances. An eventual link of aPE antibodies with failure of in vitro fertilization is also considered as well as uncommon clinical associations of aPE that are also discussed.

Yellow fever vaccination and Kawasaki disease.

DISCUSSION This is the first report of the use of oral linezolid for the successful treatment of staphylococcal liver abscess in CGD. Linezolid is an oxazolidinone antibiotic that has a bacteriostatic action by inhibition of the 70s ribosomal initiation complex. Linezolid is rapidly and completely absorbed after oral administration. It is used in complex or resistant gram-positive infections, and is an oral option where intravenous therapy would be the normal route of administration. In this case it was used with caution and as a last resort because of reports of serious adverse events related to mitochondrial toxicity in treatment courses beyond 28 days. Short courses of linezolid are well tolerated in children. Common adverse events include nausea, vomiting, and diarrhea. Teeth and tongue discoloration with taste disturbance has also been reported. Anemia and thrombocytopenia are frequently seen but are reversible and often do not require discontinuation of therapy. The more serious adverse events relate to its mitochondrial toxicity. The main risk of long-course therapy is irreversible peripheral neuropathy; optic neuropathy can also occur but rapidly improves after discontinuation of therapy. Michel Erlewyn-Lajeunesse, MRCPCH, DM Woolf Walker, BM, MRCPCH Adriana Basarab, MRCP, FRCPath Efrem Eren, FRCPath, PhD Nadeem Afzal, MRCPCH, MRCP(UK) Southampton University Hospitals NHS Trust Southampton, United Kingdom

Decreased Levels of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Patients with Primary Antiphospholipid Syndrome

IntroductionCD4+CD25+Foxp3+ regulatory T (Treg) cell dysfunction has been documented in various autoimmune disorders, but not in antiphospholipid syndrome (APS) so far.MethodsIn this cross-sectional study, we aim to investigate CD4+CD25+Foxp3+ Treg cells, CD3+CD19− T cells and CD3−CD19+ B cells in patients with primary APS and healthy controls. Cell subtypes were immunophenotyped using specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti-Foxp3, anti-CD19 PE) and flow cytometry.ResultsTwenty patients with APS and 20 age- and sex-matched controls were studied. The percentage of total lymphocytes, activated Th cells (CD4+CD25+), Treg cells and CD3−CD19+ B cells were found significantly lower in APS patients as compared to controls (all p < 0.05).ConclusionA dysfunction in CD4+CD25+Foxp3+ Treg cells may represent one of the mechanisms leading to autoimmunity in APS patients. The decreased number of CD3−CD19+ B cells of APS patients warrants further elucidation.

Autoantibodies to the Atheroma Component Beta2-Glycoprotein I and Risk of Symptomatic Peripheral Artery Disease

Peripheral artery disease (PAD) is mostly related to atherosclerosis. Autoimmunity and, in particular, antibodies to cardiolipin (aCL) and phospholipid cofactors such as beta2-glycoprotein I (beta2-gpI) might influence the development of atheroma. Beta2-glycoprotein I (beta2-gpI) has been found in atheroma. It has previously been shown that immunoglobulin A (IgA) anti-beta2-gpI antibodies are associated with a risk of cerebral ischemia and myocardial infarction. This case control study aimed to determine whether elevated levels of aCL/anti-beta2-gpI antibodies are associated with a risk of symptomatic PAD (sPAD). Cases comprised a nonselected population of patients with sPAD (intermittent claudication or critical ischemia). Patient recruitment was based on arteriography changes. Controls were selected from patients admitted to orthopedic wards as a result of fractures or muscle-ligamentous disorders. Age, sex, race, hypertension, smoking, diabetes mellitus, and hypercholesterolemia were evaluated as risk factors in both groups. IgG/IgM/IgA aCL and anti-beta2-gpI were detected by enzyme-linked immunoabsorbant assays (ELISA). To estimate the grade of association of antibodies with sPAD, odds ratios (OR) were calculated. Logistic regression was utilized for adjustment of confounding factors. Seventy-seven cases and 93 controls were studied. The mean age was 61.5 years for cases and 47.5 years for controls (p <0.001). Among the risk factors evaluated, the presence of hypertension showed the strongest association with sPAD (OR 12.1; 95%CI 5.8—30). The presence of IgA anti-beta2-gpI was independently associated with sPAD (OR 5.4; 95%CI 1.8—15.8; p = 0.01). IgA aCL was strongly associated with the outcome (nonadjusted OR 11.5 after Agresti correction). IgA aCL and IgA anti-beta2-gpI antibodies were not associated with any known risk factors for sPAD or with arteriography changes. The occurrence of these autoantibodies might represent one of the links between autoimmunity and atherosclerosis in patients with sPAD.

Scalp seborrheic dermatitis: prevalence and associated factors in male adolescents

Background  The prevalence of seborrheic dermatitis (SD) in the general population is variable in the literature. Factors associated with SD are not well understood.

Antimaláricos e perfil lipídico em pacientes com lúpus eritematoso sistêmico

A beneficial influence of antimalarials on lipid profile of systemic lupus erythematosus (SLE) patients has been recently claimed. In this cross-sectional study, we evaluated the effect of chloroquine on cholesterol levels of a Brazilian population with SLE. Sixty patients were studied, 95% females. Mean age was 48.7 years (SD 13.3 years). Overweight or obesity was documented in 27 cases (45%). Thirty-four patients (56.6%) were using chloroquine in standard dosage, while 33 (55%) were on corticosteroids. Hypercholesterolemia was present in 26 patients (43.3%), while low HDL cholesterol levels were seen in 18 cases (30%). Normal cholesterolemia was documented equally in users and non-users of antimalarials (P > 0.20). After adjustment for statin and corticosteroid intake by multivariate analysis, cholesterol and HDL-cholesterol levels did not significantly differ in users or non-users of chloroquine (P > 0.05). There was no association of chloroquine intake with low body mass index (P = 0.314). Our findings suggest that antimalarial intake by itself does not distinguish cholesterol profiles in SLE patients.

The antiphospholipid syndrome and Tregs.

The antiphospholipid syndrome (APS) is an intriguing autoimmune thrombophilia of young adults with a complex pathogenesis. Antiphospholipid antibodies (aPL) promote activation of platelets and endothelial cells, inhibition of fibrinolysis, release of tissue factor, and complement activation [1]. Dendritic cells may represent a link between aPL and endothelial dysfunction in APS [2]. Recently, an increased activity of the IL-23/IL-17 axis was reported in APS [3]. It is tempting to speculate that cellular regulatory mechanisms are failing in this pathogenic context. Over the last decade, the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in the control of immune response has been extensively studied. Thymus-derived natural Treg (nTreg) usually express Helios (an Ikaros family transcription factor), but recently Heliosnegative nTreg subsets were described. The CD25high is the most importantmarker of diverse induced Treg phenotypes. Treg cells can inhibit antigen-specific response by cell-to-cell contact, secrete regulatory molecules such as IL-10 and transforming growth factor beta (TGFbeta), and block memory T cells [4]. Quantitative or functional defects of Treg cells are likely to switch the immune system toward autoimmunity [5]. Treg dysfunction has been documented in a number of systemic autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis and primary Sjögren syndrome [6]. Little is known, however, on the role of regulatory cells in the physiopathogenesis of APS. The first study addressing B and T subsets in primary APS is dated from 1994, a “pre-Treg era”. Lower total lymphocyte count, expansion of naive CD4 cells and lower proportion of memory CD4 cells were reported in the APS group as compared to controls [7]. In 1995, it was found that the injection of CD8 cells from bromocriptine-treated mice with SLE or primary APS abrogated the disease in the respective experimental models, suggesting a non-specific immunosuppressive role for these cells [8]. In 2009, a study demonstrated that patients with obstetric APS had lower percentages and absolute counts of CD4+CD45RA-CCR7effector memory cells. Of interest, increased percentages of CD8+DR+T cells and of naive B cells associatedwith occurrence of thrombosis in patients with obstetric APS. Tregs were not investigated in this study [9]. In women with recurrent miscarriages, a recent report accounted for decreased number of Tregs leading to a Th1 and Th17 proinflammatory response in pregnancy [10]. Our group recently evaluated B and T cell subsets (Tregs for the first time) in patients with primary APS. The percentage of total lymphocytes, activated Th cells (CD4+CD25+), CD4(+)CD25(+)Foxp3(+) Treg cells and CD3(−)CD19(+) B cells were significantly lower in the