Polyspecific IgG Research Articles

Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients

Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14+ cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.

Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis

Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases.

Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis

BackgroundThe diagnosis of multiple sclerosis (MS) is currently based solely on clinical and magnetic resonance imaging features. However, histopathological studies have revealed four different patterns of lesion pathology in patients diagnosed with MS, suggesting that MS may be a pathologically heterogeneous syndrome rather than a single disease entity.ObjectiveThe aim of this study was to investigate whether patients with pattern I MS differ from patients with pattern II or III MS with regard to cerebrospinal fluid (CSF) findings, especially with reference to intrathecal IgG synthesis, which is found in most patients with MS but is frequently missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive encephalomyelitis.MethodsFindings from 68 lumbar punctures in patients who underwent brain biopsy as part of their diagnostic work-up and who could be unequivocally classified as having pattern I, pattern II or pattern III MS were analysed retrospectively.ResultsOligoclonal bands (OCBs) were present in 88.2% of samples from pattern I MS patients but in only 27% of samples from patients with pattern II or pattern III MS (P < 0.00004); moreover, OCBs were present only transiently in some of the latter patients. A polyspecific intrathecal IgG response to measles, rubella and/or varicella zoster virus (so-called MRZ reaction) was previously reported in 60–80% of MS patients, but was absent in all pattern II or III MS patients tested (P < 0.00001 vs. previous cohorts). In contrast, the albumin CSF/serum ratio (QAlb), a marker of blood–CSF barrier function, was more frequently elevated in samples from pattern II and III MS patients (P < 0.002). Accordingly, QAlb values and albumin and total protein levels were higher in pattern II and III MS samples than in pattern I MS samples (P < 0.005, P < 0.009 and P < 0.006, respectively).ConclusionsPatients with pattern II or pattern III MS differ significantly from patients with pattern I MS as well as from previous, histologically non-classified MS cohorts with regard to both intrathecal IgG synthesis and blood–CSF barrier function. Our findings strongly corroborate the notion that pattern II and pattern III MS are entities distinct from pattern I MS.

Intravenous immunoglobulin as clinical immune-modulating therapy.

Intravenous immunoglobulin is derived from pooled plasma from thousands of healthy donors and contains polyspecific IgG. In addition to its indication for immunodeficiency disorders, immunoglobulin is used in a variety of immune-mediated disorders. Several issues remain unresolved: optimal dose,

Polyspecific IgG against mumps, rubella and measles in paediatric population with neuroinflammation process in vaccine failure conditions

Event Abstract Back to Event Polyspecific IgG against mumps, rubella and measles in paediatric population with neuroinflammation process in vaccine failure conditions Ivonne M. Iglesias Gonzalez1*, Barbara Padilla Docal1, Alberto J. Dorta Contreras1 and Ricardo Junco Calzadilla1 1 Laboratorio Central de Liquido Cefalorraquideo (LABCEL) Facultad Miguel Enriquez Univesidad de Ciencias Medicas de la Habana, Cuba Introduction: The vaccines combined trivalent against mumps, rubella and measles have been used during years in United States and in the greater part of the European countries. Also several Latin American countries have included this vaccine in their national vaccination program. Objective: Determine according to the polyspecific answer anti IgG mumps, rubella and measles in a children population with neuroinfammation process if a vaccine failure was produced. Material and methods: Pediatric patients suffering from viral meningoencephalitis during 2009-12. Previously, the patients were immunized with against with a trivalent vaccine againt mumps, rubella and measles. Serum and cerebrospinal fluid (CSF) IgG and albumin were quantified by immunodiffusion to determine intrathecal IgG synthesis and virus specific IgG antibody index by ELISA technique. Results: IgG intrathecal synthesis were presented without blood-CSF dysfunction. CSF and serum anti-mumps IgG were significant positive correlationate and between measles antibody index with age of the patients and answer time but not in anti rubella and anti measles antibody index with age and answer time and vaccination year. Conclusions: A vaccination failure was produced in this children population according to their polyspecific IgG antibodies against measles, rubella and mumps and correlated with epidemiology findings. Keywords: Vaccine failure, neuroimmunology response, Measles, Mumps Vaccine, Rubella Vaccine Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Immunotherapy Citation: Iglesias Gonzalez IM, Padilla Docal B, Dorta Contreras AJ and Junco Calzadilla R (2015). Polyspecific IgG against mumps, rubella and measles in paediatric population with neuroinflammation process in vaccine failure conditions. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00077 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Mar 2015; Published Online: 14 Sep 2015. * Correspondence: Dr. Ivonne M Iglesias Gonzalez, Laboratorio Central de Liquido Cefalorraquideo (LABCEL) Facultad Miguel Enriquez Univesidad de Ciencias Medicas de la Habana, Havana, Havana, 10700, Cuba, iigonzalez@infomed.sld.cu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ivonne M Iglesias Gonzalez Barbara Padilla Docal Alberto J Dorta Contreras Ricardo Junco Calzadilla Google Ivonne M Iglesias Gonzalez Barbara Padilla Docal Alberto J Dorta Contreras Ricardo Junco Calzadilla Google Scholar Ivonne M Iglesias Gonzalez Barbara Padilla Docal Alberto J Dorta Contreras Ricardo Junco Calzadilla PubMed Ivonne M Iglesias Gonzalez Barbara Padilla Docal Alberto J Dorta Contreras Ricardo Junco Calzadilla Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effect of IVIg on human dendritic cell-mediated antigen uptake and presentation: Role of lipid accumulation

Intravenous immunoglobulin (IVIg) is a therapeutic preparation consisting of pools of normal, polyspecific IgG antibodies obtained from plasma of several thousand healthy individuals. In addition to its use in primary and secondary immune deficiency, IVIg is increasingly used in the therapy of a large number of autoimmune conditions. Despite its successful use in immunopathologies for over two decades, the precise mechanisms underlying the therapeutic benefit have not been fully elucidated. We and others have demonstrated that IVIg inhibits the antigen uptake and presentation by dendritic cells (DC). Here we report that IVIg-mediated inhibition of uptake and processing of antigens is associated with an increased accumulation of lipid as analyzed by flow cytometry and electron microscopy. As accumulation of lipids in DC is known to impart tolerogenic properties, these findings unravel novel link between antibodies and intracellular physiology of innate cells and may further uncover novel immunoregulatory mechanisms of IVIg in auto-inflammatory diseases.

Patterns of intrathecal autoreactive antibodies in MS using antigen microarrays

The role of autoreactive antibodies in multiple sclerosis (MS) has received intense attention since the discovery of oligoclonal immunoglobulin (Ig) bands in the majority of patients with MS.1 However, many questions remain. We still do not know whether the intrathecal production of Ig is an epiphenomenon of CNS autoimmunity, resulting from growth factor–driven expansion of long-lived B cells in the meningeal compartment or whether Ig production from antigen-driven proliferation of B-cell clones contributes to CNS immunopathology.2 CSF Ig from oligoclonal bands is produced by CSF B lineage cells3 and primarily recognizes epitopes of multiple neurotropic viruses and Epstein-Barr virus antigens.4,5 However, antimyelin antibodies also occur in the serum and CSF of patients with MS.6 In this issue of Neurology ®, Quintana et al.7 describe an array platform that can be used to detect serum and CSF antibodies directed against a large number of linear epitopes of CNS antigens, including not only peptides derived from myelin and astrocytic proteins but also heat shock proteins or even lipid constituents. The intrathecally produced (polyspecific) IgG class response was heterogeneous in individual patients with MS, and steroid treatment was associated with decreased intrathecal autoantibody reactivity. The authors concluded that the antigen array technology is a …

Intravenous immunoglobulin therapy in rheumatic diseases

Prepared from the collective plasma of several thousand people, therapeutic intravenous immunoglobulin (IVIg) consists mostly of human polyspecific IgG. In addition to its use in primary and secondary immune deficiencies, IVIg is used in the treatment of several rheumatic conditions, including Kawasaki disease, dermatomyositis and antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. In these diseases, IVIg therapy generally involves the use of 2 g/kg administered over either 2 or 5 consecutive days. However, dosage regimens have not been thoroughly explored, and indications for IVIg in most rheumatic diseases, such as systemic lupus erythematosus, polymyositis and catastrophic antiphospholipid syndrome, derive from its off-label usage. Randomized clinical trials are warranted to support the evidence-based use of IVIg, and to identify the ideal administration protocols to maximize the benefits of what is a limited resource. Further research to improve the therapeutic application of IVIg relies essentially on the conception of next-generation immunoglobulin preparations and optimization of combined therapies with immunomodulatory drugs and biologic agents.

Incidence of Isolated Heparin-Induced Thrombocytopenia and the Risk of Developing Subsequent Thrombosis Using the New IgG Specific Anti-PF4/Heparin ELISA

AbstractAbstract 1448 BACKGROUND:The new IgG specific ELISA for anti-platelet factor 4 (PF4)/heparin antibody is recently introduced for the diagnosis of heparin-induced thrombocytopenia (HIT). It is as sensitive but more specific than the poly-specific IgG, M, A ELISA. About 50% of patients testing positive for the anti-PF4/heparin antibody have thrombocytopenia alone as initial manifestation of HIT without thrombosis (isolated HIT). These patients are thought to be at high risk (≂f30%) for developing thrombosis within next 28 days. The incidence of isolated HIT using IgG-specific ELISA is unknown. OBJECTIVES:Evaluate the incidence of isolated HIT using the IgG specific anti-PF4/heparin ELISA and the risk of developing subsequent thrombosis in these patients. PATIENTS AND METHODS:We performed a retrospective observational study of patients being tested for the anti-PF4/heparin antibody at our institution from December 2008 to May 2010 using the IgG-specific anti-PF4/heparin ELISA with a two-step assay using high dose heparin in the second step to demonstrate heparin specificity. A positive test was defined as optical density (OD) >0.4 with >50% inhibition. RESULTS:319 patients were tested during the study period. 23 (7.2%) patients were diagnosed with HIT based on clinical findings (4T score) and ELISA. 16/23 (70%) had thrombosis at diagnosis whereas 7/ 23 (30%) had isolated HIT. All 7 patients with isolated HIT had follow up data for at least 3 months after diagnosis. Only 2/7 were treated with direct thrombin inhibitors (DTI) and 4/7 were treated with warfarin for at least 1 month. While only 3 of the 7 isolated HIT patients had compression ultrasonography to rule out occult lower extremity thrombus, none of these 7 patients (including 4 with an OD of >1.0) developed symptoms or signs of thrombosis in the subsequent 3 months after the diagnosis of isolated HIT. CONCLUSION:The incidence of isolate HIT in this study (7.2%) is significantly lower than previously reported by others and our own historical patients (57.4%, Altuntus et al, Euro J of Haematology 2008) using the IgG, M, A poly -specific anti-PF4/heparin ELISA (z value 2.092, p=0.036). It is possible that many patients previously thought to have HIT by the poly-specific anti-PF4/heparin ELISA assay were false positive. Using the IgG-specific anti-PF4/heparin ELISA not only improved the specificity of the ELISA assay, it also reduced the number of patients with isolated HIT significantly who also seem to have lower risk of developing subsequent thrombosis.Pt4T scoreOD% inhibitionNadir plateletDTIWarfarin after DTIThrombosis at follow up151.8779752YesYesNo262.0989240YesYesNo340.5119779NoNoNo440.479105107NoNoNo541.22710557NoNoNo641.213100104NoYesNo740.4928450NoYesNo Disclosures:No relevant conflicts of interest to declare.

Analysis of camelid antibodies for antivenom development: Neutralisation of venom-induced pathology

Camelid IgG has been reported to be less immunogenic, less able to activate the complement cascade and more thermostable than IgG from other mammals, and has the ability to bind antigens that are unreactive with other mammalian IgGs. We are investigating whether these attributes of camelid IgG translate into antivenom with immunological and venom-neutralising efficacy advantages over conventional equine and ovine antivenoms. The objective of this study was to determine the preclinical venom-neutralising effectiveness of IgG from camels immunised with venoms, individually or in combination, of the saw-scaled viper, Echis ocellatus, the puff adder, Bitis arietans and the spitting cobra, Naja nigricollis – the most medically-important snake species in West Africa. Neutralisation of the pathological effects of venoms from E. ocellatus, B. arietans and N. nigricollis by IgG from the venom-immunised camels, or commercial antivenom, was compared using assays of venom lethality (ED 50), haemorrhage (MHD) and coagulopathy (MCD). The E. ocellatus venom ED 50, MHD and MCD results of the E. ocellatus monospecific camel IgG antivenom were broadly equivalent to comparable ovine (EchiTAbG ®, MicroPharm Ltd, Wales) and equine (SAIMR Echis, South African Vaccine Producer, South Africa) antivenoms, although the equine antivenom required half the amount of IgG. The B. arietans monospecific camel IgG neutralised the lethal effects of B. arietans venom at one fourth the concentration of the SAIMR polyspecific antivenom (a monospecific B. arietans antivenom is not available). The N. nigricollis camel IgG antivenom was ineffective (at the maximum permitted dose, 100 μl) against the lethal effects of N. nigricollis venom. All the equine polyspecific antivenoms required more than 100 μl to be effective against this venom. The polyspecific camel IgG antivenom, prepared from five camels, was effective against the venom-induced effects of E. ocellatus but not against that of B. arietans and N. nigricollis venoms. No direct correlation was evident between either camel IgG relative avidity or titre and the effectiveness of venom neutralisation in preclinical assays.

Intravenous immunoglobulin increases survival time in the acute phase of experimental Chagas disease

Chagas disease induced by Trypanosoma cruzi (Tc) infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are insufficient and largely inadequate. Intravenous immunoglobulin (IVIg) is a therapeutic preparation containing normal polyspecific IgG obtained from plasma pools of several thousand healthy donors and is used in several autoimmune, inflammatory and infectious diseases. In the study of heart from mice chronically infected with Tc, we observed that IVIg restores type 1 atrioventricular block or bradycardia. In the present study, we investigated the effects of IVIg in acute Tc infection. Intravenous immunoglobulin administration after the first week of infection was associated with an increase in survival time. Taken together, results observed in the chronic and in the acute phase associate IVIg treatment with a favourable outcome in T. cruzi infection.

A close look at human IgG sialylation and subclass distribution after lectin fractionation

Polyspecific human IgG preparations are indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. In addition, intraveneous IgG (IVIG) is used to treat patients with autoimmune and systemic inflammatory diseases. Lectin chromatography on Sambucus nigra agglutinin stood at the cradle of the hypothesis that the anti-inflammatory properties depend on sialylation of the N-glycans in the Fc region of IgG. A detailed analysis of fractions obtained by lectin chromatography revealed that binding of IVIG is essentially mediated by Fab glycosylation. Moreover, experiments with a monoclonal antibody from a human cell line and IVIG Fc fragments indicated that at least two sialic acids in the Fc region of an antibody are required for lectin binding. Such glycoforms contain either two monosialylated glycans or a disialylated glycan and constitute 1% or less of the total human IgG. Arguably this small proportion holds the entire anti-inflammatory potency. A new mass spectrometric quantification method of IgG subclass ratio revealed that the IVIG Fc preparation essentially consists of IgG1. This observation may be relevant when studying the effect of human Fc in murine models of inflammation because mouse IgG subclasses differ substantially in their interaction with receptors.

Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis

Anti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21 sera from patients with acute systemic vasculitis following incubation with normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive binding assays using F(ab')2 fragments from IVIg and affinity chromatography of ANCA IgG on Sepharose-bound F(ab')2 fragments from IVIg. Co-incubation of sera from patients with acute systemic vasculitis with paired autologous remission stage sera also resulted in inhibition of ANCA activity in acute sera. Remission sera contain IgM and IgG capable of interacting with beta and or alpha idiotypes of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of expression of ANCA activity in whole serum from patients in remission from systemic vasculitis, which were found to contain high titres of ANCA IgG. These observations suggest that remission of systemic vasculitis is associated with the generation of anti-idiotypes against autoantibodies rather than the suppression of production of ANCA autoantibodies. IVIg may modulate the activity of systemic vasculitis in vivo.

Effect of IgG for intravenous use on Fc receptor-mediated phagocytosis by human monocytes

Polyspecific IgG given intravenously at high doses (IVIG) is used for immunomodulatory therapy in autoimmune diseases such as idiopathic thrombocytopenic purpura and myasthenia gravis. It is assumed that the clinical effect is brought about in part by a modulation of mononuclear phagocyte function, in particular by an inhibition of Fc receptor (FcR) mediated phagocytosis. In the present study, the effect of IVIG on FcR-mediated phagocytosis by monocytes was analysed in vitro. Since monocytes exposed to minute amounts of surface-bound IgG displayed impaired phagocytosis of IgG-coated erythrocytes (EA), the effect of IVIG was studied with mononuclear cells suspended in teflon bags in medium containing 10% autologous serum and IVIG (2-10 mg/ml). Monocytes pre-exposed to IVIG and then washed, displayed impaired ingestion of EA when compared with control cells cultured in 10% autologous serum only. The decrease in phagocytosis was observed with sheep erythrocytes treated with either rabbit IgG or bovine IgG1 and with anti-D-treated human erythrocytes. This suggests that phagocytosis via both FcR type I (FcRI) and type II (FcRII) was decreased. The impairment of phagocytosis was dependent on the presence of intact IgG and was mediated by IVIG from nulliparous donors and from multigravidae to the same extent, suggesting that alloantibodies contained in IVIG have a minor role in modulating FcR-mediated phagocytosis by monocytes. A flow cytometric analysis using anti-FcRI, FcRII and FcRII monoclonal antibodies showed that IVIG treatment upregulated FcRI expression but did not significantly alter the expression of FcRII and FcRIII.

Morbidity and Mortality of Patients With Invasive Group A Streptococcal Infections Admitted to the ICU

<h3>Study objectives</h3> To describe the clinical features and outcome of patients with invasive group A streptococcal (GAS) infections admitted to the ICU. <h3>Design</h3> Prospective, population-based surveillance for invasive GAS infections was conducted in Ontario from January 1992 until June 2002. All 62 patients meeting clinical and/or histopathologic criteria for invasive GAS who were admitted to the ICUs of four university-affiliated hospitals in Toronto, Canada were included. Demographic and clinical information were obtained retrospectively by chart review. ICU morbidity data included the occurrence of organ dysfunction (renal, hepatic, coagulation, ARDS), treatment, and interventions such as hemodialysis and mechanical ventilation. <h3>Measurements and results</h3> ARDS developed in 34%, renal dysfunction developed in 55%, hepatic dysfunction developed in 64%, and coagulopathy developed in 69% of patients. A total of 56% of patients were treated with IV polyspecific IgG (IVIG), 81% were intubated and placed on mechanical ventilation, and 21% required renal replacement therapy. The median durations of ICU and hospital stay were 5.3 days and 15.0 days, respectively. The overall mortality was 40%. Mortality correlated directly with acute physiology and chronic health evaluation II score and the number of dysfunctional organs. Survivors were younger, had lower severity of illness scores, fewer dysfunctional organs, and were less likely to have shock or to receive treatment with vasopressors, mechanical ventilation, or pulmonary artery catheters. There was no association between the use of IVIG, surgical intervention, or clindamycin, and survival. Variables independently associated with mortality on multivariable analysis were the presence of coagulopathy (p = 0.0005) and liver dysfunction (p = 0.0123). <h3>Conclusions</h3> Patients with invasive GAS infection admitted to the ICU have a high mortality rate. In this group of patients, coagulopathy and liver failure were independently associated with mortality. We did not observe any association between the use of IVIG, surgical intervention, or clindamycin, and survival.

Effect of IgG Therapy on Lymphocyte Subpopulations in the Peripheral Blood of Kuwaiti Women Experiencing Recurrent Pregnancy Loss

Intravenously administered polyspecific IgG is being increasingly used as an immunomodulating therapy with controversial beneficial outcome. The aim of this study was to evaluate the effects of IgG infusion on peripheral T-cell subpopulations in women with recurrent pregnancy loss (RPL). Fifteen women with a history of three previous RPL between 6 and 22 weeks of gestation and positivity for the antiphospholipid antibody syndrome (APS) were randomized to one of two treatment groups: (a) an intravenous immunoglobulin therapy group (RPL-IVIg; 7 patients), 500 mg IVIg/kg/month and (b) a placebo-treated group given multivitamins (8 patients). Control groups comprised either normal pregnant women without APS (10 patients) or non-pregnant women. The T-cell markers were characterized using a monoclonal antibody panel including CD3, CD4, CD8, CD25, CD29, CD38, CD45RA, CD45RO, CD54 and HLA-DR. Analysis was performed with a two-color fluorescent-activated flow cytometer. In the first trimester, the percentage of CD4+CD25+, CD4+CD45RO+, CD8+HLA-DR+, and CD8+CD38+ populations were reduced in the multivitamin group compared to normal pregnant women (p < 0.05) while in the RPL-IVIg group only CD4+CD25+ cells were reduced (p < 0.05). By the second trimester, CD3+CD16+CD56+ was significantly higher in multivitamin- than in IVIg-treated women (p < 0.05). The percentage of CD4+HLA-DR+ was significantly higher in the two RPL groups compared to normal pregnant women (p < 0.05). IVIg therapy in women with RPL was associated with a significant reduction in CD3+CD16+CD56+ and CD4+CD25+. This may contribute to the suppression of immune-mediated processes contributing to premature abortion.

Anti-Diego a Red Blood Cell Alloantibody as a Possible Cause of Anemia in a 3-Week-Old Infant

Our aim in this case report was to describe anemia caused by anti-Diego a red blood cell (RBC) antibody in a 3-week-old infant derived during pregnancy to low-frequency Diego a RBC antigen. Pre- and postnatal maternal serum screening for unexpected RBC antibodies and determination of RBC antibody specificity in the sera of the mother and child and in the elute of the child were performed by use of microcards (Diamed, Basel, Switzerland; BioVue, Ortho Clinical Diagnosis, Raritan, NJ, USA) with commercially prepared test RBCs (Diamed, Ortho Clinical Diagnosis, and Gamma Biologicals, Houston, TX, USA) at 37°C and indirect antiglobulin test (IAT) according to manufacturer instructions. Direct antiglobulin test (DAT) was performed by use of microcards (Diamed, Ortho Clinical Diagnosis) with both polyspecific and monospecific IgG anti-human globulin. Di a antigen was determined on maternal, paternal, and infant's red cells by commercial reagent (Gamma Biologicals). Determination of RBC antibody specificities in maternal and child sera and in the child's RBC eluate showed 2+ positive reactions only with two Di a+ test RBCs. Father and baby were positive and mother was negative for Di a antigen. When a newborn has positive DAT and there are no clinical reasons for this, the possibility of positive DAT resulting from alloimmunization to low-frequency RBC antigens should be considered.

Relative neutralizing activity in polyspecific IgM, IgA, and IgG preparations against group A streptococcal superantigens.

In this study we compared the ability of different immunoglobulin (Ig) preparations containing IgG, IgM, and/or IgA to neutralize the activity of streptococcal pyrogenic exotoxin A (SpeA) or culture supernatant from a clinical group A streptococcal isolate. All Ig preparations markedly inhibited the mitogenic and cytokine-inducing activity of SpeA and culture supernatant at concentrations of 0.05-0.5 mg/mL, and at 0.5 mg/mL, most caused 95-100% inhibition of both stimuli. A significantly higher (P< or =.05) inhibition of SpeA was achieved by Pentaglobin (IgG, IgM, and IgA) and IgAbulin (IgA and IgG), as compared with pure IgG preparations. IgM- and IgA-enriched preparations had significantly higher inhibitory activity against SpeA than against culture supernatant, whereas the reverse was true for the IgG preparations (P< or =.05). The data show that IgM and IgA are potent inhibitors of specific streptococcal superantigens. These findings may have implications for the optimization of immunotherapy in invasive streptococcal infections.

Antibodies to the cytoplasm, cell membrane and nuclear membrane of malignant neoplasms in pooled normal human polyspecific immunoglobulin G.

IVIg is a preparation of normal polyspecific IgG obtained from pooled plasma of a large number of healthy donors. IVIg treatment of patients with chronic lymphocytic leukemia induced a reduction in the total number of lymphocytes in the peripheral blood. Regression of Kaposi's sarcoma was also noted in an HIV patient treated with IVIg. The aim of this study was to determine whether F(ab')2 prepared from IVIg binds to cellular structures of different tumor tissues. Biotinylated F(ab')2 was prepared from 3 different preparations of IVIg and from affinity purified IgG from a patient with multiple myeloma. Direct immunohistochemistry using a streptavidin peroxidase staining method was performed on biopsy samples of 18 different tumor tissues. Positive staining of the cytoplasm, cell membrane and nuclear membrane of several types of malignant tumors by F(ab')2 from IVIg was immunohistochemically demonstrated. Nuclear staining of tumor cells by IVIg was rare. IVIg bound to different tumors of epithelial origin, especially colon carcinoma, breast carcinoma and squamous cell carcinoma of the lung. Malignant tumors of mesenchymal origin such as leiomyosarcoma have also demonstrated positive staining by IVIg. IVIg contains antibodies to the cytoplasm, nuclear membrane and cell membrane of different malignant tumors especially of epithelial origin. This binding might provide a basis for the assumption that IVIg treatment of cancer patients may induce antibody dependent cell mediated cytotoxicity response against tumors, and implies that it can be potentially beneficial as adjuvant treatment of malignant diseases.

Polyspecific self-reactive antibodies in individuals infected with human immunodeficiency virus facilitate T cell deletion and inhibit costimulatory accessory cell function.

Self-reactive polyspecific IgG antibodies (PSAs) arise in human immunodeficiency virus (HIV)-seropositive subjects before they develop AIDS. Self-reactive PSA levels correlate with the destruction of CD8 T cells in HIV-infected individuals and mediate the antibody-dependent cellular toxicity-based destruction of human T cells in tissue culture. PSAs react across the species barrier and bind to T cell antigens in mice. Such reactivity with mouse lymphocytes was not detected in normal human serum. Injection of human PSA IgG causes massive T cell depletion in the spleen, lymph nodes, and thymus in mice: evidence that PSA IgG facilitates T cell destruction in vivo. In addition to facilitating macrophage cytotoxicity, self-reactive PSA IgG inhibits the macrophage-mediated activation of T cells with antigen receptor-specific monoclonal antibody or with antigen. Exogenous costimulatory stimuli or interleukin (IL)-12 can reverse the inhibition. In contrast, exogenous IL-10 mimics this inhibition. These data implicate PSA IgG as a pathogenic factor in the development of HIV disease.