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Intravenous immunoglobulins (IVIg) exert a broad range of immunoregularoty functions that provide a basis for the beneficial effects of IVIg in autoimmune and systemic inflammatory disorders. This review focuses on the effects f IVIg on humoral and cellular immunity that may be of relevance for the treatment of inflammatory neurological diseases. [ABSTRACT FROM AUTHOR]

Abstract Natural autoantibodies (NAbs), produced by B-1 B-cells, are directed against autoantigens and pathogens. NAbs can capture and present antigen to T helper cells thereby initiating adaptive immunities. It is proposed that screening for NAbs against pathogens will predict the strength of an antigen-induced immune response and could be used as a tool for vaccine development. [ABSTRACT FROM AUTHOR]

Therapeutic polyclonal intravenous immunoglobulin (IVIg) consists of normal IgG obtained from the pools of plasma of several thousand healthy blood donors. IVIg is used as substitutive treatment of primary and secondary immunodeficiences. Since the first study of Paul Imbach who demonstrated the beneficial effect in idiopathic thrombocytopenic purpura, IVIg is also used in a number of autoimmune and inflammatory diseases. The immunoregulatory effects of IVIg in autoimmune diseases depend on the interaction of Fc portion of immunoglobulins with Fc receptors and on the selection of lymphocyte repertoires of patients through variable regions of infused immunoglobulins. IVIg modulates the activation and effector functions of B and T lymphocytes, neutralizes pathogenic autoantibodies, interferes with antigen presentation and has a strong anti-inflammatory effect which depends on its interaction with the complement system, cytokines and endothelial cells. The immunomodulatory potential of IVIg in patients is thus a result of a variety of complex mechanisms that act in a synergy. [Copyright &y& Elsevier]

The epidemiological role of small ruminants in foot-and-mouth disease (FMD) outbreaks has been generally neglected. Although, the disease in these species is sub-clinical in nature, their role as virus carriers represents a reservoir for further infection and spread of disease. Data on the usefulness of polyvalent FMD vaccine (FMDV) in goats is scant. Thus, the present study was undertaken to evaluate the benefits of a highly potent polyvalent FMDV in goats. In the present investigations, FMDV quadrivalent double oil emulsion (Montanide ISA 206) vaccines were tested in goats at reduced doses of 2 ml per animal (antigen payload 3.5 μg per serotype per dose). The oil adjuvant elicited superior immune response at any given period than aluminium hydroxide gel (AGS) vaccine and the rapidity of development of response was quicker. The duration of immunity also appeared to be maintained for long period. The differences in immune response between two adjuvant groups were statistically significant (P<0.05). The differences were apparent even in kinetics of immune response. Unlike cattle, goats were found to be late responders for oil-adjuvanted vaccine. Our results indicate possible universal usage of double oil emulsion vaccines for disease control programs irrespective of species of animals. [Copyright &y& Elsevier]

Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals. The multiplicity of FMDV serotypes in animals poses a central problem in the policy of vaccination and is of much concern to health authorities. Hence it is the practice of vaccination with polyvalent vaccine for prophylactic measure. In the present report, we analysed the early antibody responses elicited by FMDV quadrivalent (FMDV O, A, C and Asia 1 serotypes) double emulsion (Montanide ISA 206) vaccines in cattle. We observed variations between various viral serotypes in eliciting early antibody response although neutralizing antibody response against all the four serotypes were detected as early as fourth day following vaccination. The duration of immunity also appeared to maintain for long period. The neutralizing antibody titres were maintained well above 2 log10 even after 6 months of vaccination irrespective of serotypes. Thus, allows the possibilities of two vaccinations per year for the maintenance of herd immunity. [Copyright &y& Elsevier]

Summary. Idiotypic vaccination has proven successful in several animal models and human trials. Here we suggest that the expression of cross-reactive idiotypes on factor VIII (FVIII) inhibitors of patients with haemophilia A, patients with anti-FVIII autoimmune disease and natural anti-FVIII antibodies of healthy individuals, together with the ability of anti-idiotypic reagents to neutralize anti-FVIII antibodies, provides a rationale for designing a vaccine strategy aimed at preventing the occurrence of or suppressing inhibitors, based on the induction of protective anti-idiotypes. Here we discuss the rationale supporting the concept of using idiotypic vaccination to prevent the occurrence of FVIII inhibitors in patients with haemophilia A. [ABSTRACT FROM AUTHOR]

The occurrence of factor VIII (FVIII) inhibitors is one of the major complications of the treatment of haemophilia A. We present this review as a description of the major players of the antiFVIII immune response, with particular emphasis on the nature and properties of the different antiFVIII antibodies, their mechanisms of action in inhibiting FVIII activity, their potential neutralization by antiidiotypic antibodies, and the importance of the T cell in participating in the induction of FVIII inhibitors. We briefly conclude on the avenues that remain to be explored in order to establish efficient therapeutic approaches aimed at eliminating FVIII inhibitors in patients with haemophilia A. [ABSTRACT FROM AUTHOR]

Summary: The mechanisms of action of intravenous immunoglobulins (IVIg) in autoimmune diseases are not fully understood. The fixed duration of efficacy and noncumulative effects of IVIg in immune thrombocytopenia (ITP) and acquired von Willebrand disease (AVWD) suggest other mechanisms besides immunological ones. Additionally to the peripheral destruction of platelets in ITP, their medullary hypoproduction emerged as a new paradigm with rescue of thrombopoietin receptor agonists (TPO‐RA). In an ITP mouse model, interleukin (IL)‐11 blood levels increase following IVIg. IL‐11 stimulates the production of platelets and other haemostasis factors; recombinant IL‐11 (rIL‐11) is thus used as a growth factor in post‐chemotherapy thrombocytopenia. We therefore hypothesized that IVIg induces IL‐11 over‐production, which increases platelets, VWF and factor VIII (FVIII) levels in humans and mice. First, in an ITP mouse model, we show that IVIg or rIL‐11 induces a rapid increase (72 h) in platelets, FVIII and VWF levels, whereas anti‐IL‐11 antibody greatly decreased this effect. Secondly, we quantify for the first time in patients with ITP, AVWD, inflammatory myopathies or Guillain–Barré syndrome the dramatic IL‐11 increase following IVIg, regardless of the disease. As observed in mice, platelets, VWF and FVIII levels increased following IVIg. The late evolution (4 weeks) of post‐IVIg IL‐11 levels overlapped with those of VWF and platelets. These data may explain thrombotic events following IVIg and open perspectives to monitor post‐IVIg IL‐11/thrombopoietin ratios, and to assess rIL‐11 use with or without TPO‐RA as megakaryopoiesis co‐stimulating factors to overcome the relative hypoproduction of platelets or VWF in corresponding autoimmune diseases, besides immunosuppressant. [ABSTRACT FROM AUTHOR]

La survenue de formes sévères ou critiques de COVID-19, avec nécessité d'une hospitalisation en réanimation, est associée à la présence d'anticorps anti-Interféron de classe I dans environ 10 % des cas [1]. Ces anticorps identifiés dans le contexte de la COVID-19 bloquent les molécules d'interféron (IFN) et expliqueraient chez ces patients, la survenue d'une atteinte grave de COVID-19, avec une absence d'élimination précoce du virus SARS-CoV-2. Ainsi, il s'agirait d'une forme de déficit immunitaire, acquis, dirigé contre le virus SARS-CoV-2 mais aussi potentiellement contre d'autres virus. Les caractéristiques cliniques, biologiques et morphologiques des patients présentant ces anticorps n'ont pas été décrites précisément, l'évolution des patients n'est pas connue. Une recherche d'anticorps anti-Interféron a été réalisée chez des patients ayant été pris en charge en réanimation à l'hôpital Bégin, à l'hôpital Avicenne et à l'hôpital Foch pour une COVID-19. La présence d'anticorps anti-IFNalpha2 et anti-IFNomega étaient recherchée par test ELISA puis confirmée par un test fonctionnel d'inhibition de la phosphorylation de STAT1. Les caractéristiques cliniques des patients ont été relevées à partir des dossiers médicaux. Un suivi médical a été organisé afin de suivre leur évolution sur le plan clinique, biologique et morphologique. Onze patients ont été identifiés. Il s'agissait de 11 hommes. L'âge médian au diagnostic était de 60 ans (min 36 - max 80). Parmi les autres facteurs de risques de COVID-19 grave classiquement identifiés, on retrouvait chez eux, du diabète pour 1 patient, de l'hypertension artérielle pour 6 patients et de l'obésité (IMC > 30 kg/m2) pour 5 patients. L'IMC médian était de 29,8 kg/m2 (min 24 - max 32,8). Il n'était pas noté d'antécédent remarquable, notamment pas d'argument pour un déficit immunitaire, pas d'endocrinopathie auto-immune. On retrouvait 1 BPCO, 2 asthmes, 1 coronaropathie et 1 valve aortique mécanique. Au diagnostic de COVID-19, les signes cliniques initiaux habituels de l'infection étaient retrouvés : asthénie (n = 11), fièvre (n= 10), toux (n = 5). Deux patients présentaient des diarrhées et 2 de l'insuffisance rénale aiguë, modérée. Chez 2 patients, on notait une embolie pulmonaire sur le scanner initial. L'évolution était marquée par une aggravation justifiant une admission en réanimation après une médiane de 7 jours (min 3 - max 12), pour une forme sévère chez 2 patients avec au maximum une oxygénothérapie au masque à haute concentration jusqu'à 15L/min pour 1 patient et 4L/min pour 1 autre. Une forme critique survenait chez 9 patients, avec recours à une intubation oro-trachéale pour ventilation mécanique pour 7 cas, une oxygénothérapie nasale à haut débit (OPTIFLOW) était suffisante dans 2 cas. Des pneumopathies bactériennes documentées nécessitaient une antibiothérapie spécifique dans 6 cas. Dans 10 cas, des traitements à visée spécifique du COVID-19 étaient entrepris : corticothérapie (n = 4), hydroxychloroquine (n = 4), lopinavir/ritonavir (n = 3) et tocilizumab (n = 2). En raison du développement d'un SDRA sévère, des séances d'optimisation de l'oxygénothérapie par décubitus ventral étaient entreprises chez 5 patients, avec nécessité d'un recours à une ECMO véno-veineuse pour le jeune patient de 36 ans. Afin d'éliminer les Ac antiIFN, ce dernier a également bénéficié avec succès de 3 séances d'échanges plasmatiques. Au total, 9 patients ont survécu, la durée médiane d'hospitalisaiton en réanimation était de 16 jours (min 2 - max 31). Les 2 décès sont intervenus après limitation thérapeutique pour SDRA réfractaire. Avec un suivi médian de 4,2 mois (min 1 - max 11,2), on note une bonne évolution chez l'ensemble des patients survivants, aucune réinfection n'a été observée et une régression quasi complète des lésions pulmonaires scanographiques (n = 4/5) était retrouvée à 3 mois. Lors du dernier bilan réalisé, il n'était pas constaté d'anomalie de la NFS (n = 7/8), ni syndrome inflammatoire (n = 6/7) et le taux d'immunoglobulines était normal (4/4). Cette série de cas donne une première description des patients ayant présenté une forme critique de COVID-19 avec Ac anti-IFN de classe I. En dehors de la faible prévalence de comorbidités, il ne semble pas y avoir de phénotype clinique particulier chez cette population en dehors de la prédominance masculine. [ABSTRACT FROM AUTHOR]

The administration of therapeutic factor VIII ( FVIII) to patients with haemophilia A induces the development of inhibitory anti- FVIII IgG in a substantial number of patients. For an antigen-specific immune response to develop, antigen-presenting cells ( APCs) need to mature and procure appropriate co-stimulatory signals to T cells at the time of presentation of the endocytosed antigen. The nature of the danger signals that induce APC maturation, thus initiating the anti- FVIII immune response, are yet ill-characterized. Contradictory reports on a direct effect of therapeutic FVIII on APC maturation have been released. Here, we investigated whether FVIII directly triggers Toll-like receptor 2 ( TLR2) signalling. The capacity of human recombinant FVIII to promote the maturation of a mouse bone marrow macrophage cell line (BMA) was investigated by flow cytometry. In parallel, the triggering of TLR1.2 or TLR2.6-expressing HEK293 cells by FVIII was analysed following transfection of the cells with a reporter construct for NFκB activity. In contrast, to zymosan, a known TLR2 agonist, human recombinant FVIII did not induce the maturation of mouse BMA macrophages, as analysed by the levels of expression of CD80, CD86, CD40 and I-Ab at the cell surface. Furthermore, incubation of FVIII with cells expressing TLR2 paired with TLR1 or TLR6, failed to activate NFκB, whereas NKκB activity was triggered in the presence of zymosan. Our results confirm that FVIII alone is insufficient to trigger the maturation of APCs that is required to initiate an immune response. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin (IVIG) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors. For more than 20 years, IVIG has been used in the treatment of a wide range of primary and secondary immunodeficiencies. IVIG now represents a standard therapeutic option for most antibody deficiencies. Routinely, IVIG is used in patients with X-linked agammaglobulinaemia (XLA), common variable immunodeficiency (CVID), X-linked hyper-IgM, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and selective IgG class deficiency. In addition, IVIG is used extensively in the treatment of a wide variety of autoimmune disorders. IVIG is administered at distinct doses in the two clinical settings: whereas immunodeficient patients are treated with replacement levels of IVIG, patients with autoimmune and inflammatory diseases are administered with very high doses of IVIG. Several lines of experimental evidence gathered in the recent years suggest that the therapeutic beneficial effect of IVIG in immunodeficiencies reflects an active role for IVIG, rather than a mere passive transfer of antibodies. [ABSTRACT FROM AUTHOR]

The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunodeficiencies, autoimmunity and basic research. The immunodeficiency presentations dealt with novel, rare class-switch recombination (CSR) deficiencies, attenuation of adverse events following IVIg treatment, association of immunoglobulin (Ig)G trough levels and protection against acute infection in patients with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID), and the reduction of class-switched memory B cells in patients with specific antibody deficiency (SAD). The impact of intravenous immunoglobulin on fetal alloimmune thrombocytopenia, pregnancy and postpartum-related relapses in multiple sclerosis and refractory myositis, as well as experiences with subcutaneous immunoglobulin in patients with multi-focal motor neuropathy, were the topics presented in the autoimmunity session. The interaction of dendritic cell (DC)-SIGN and α2,6-sialylated IgG Fc and its impact on human DCs, the enrichment of sialylated IgG in plasma-derived IgG, as wells as prion surveillance and monitoring of anti-measles titres in immunoglobulin products, were covered in the basic science session. In summary, the presentations illustrated the breadth of immunoglobulin therapy usage and highlighted the progress that is being made in diverse areas of basic and clinical research, extending our understanding of the mechanisms of immunoglobulin action and contributing to improved patient care. [ABSTRACT FROM AUTHOR]

Background: Viscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.Methods: Four day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 microg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyzed by allogeneic mixed lymphocyte reaction and activation of Melan-A/MART-1-specific M77-80 CD8+T cells. Cytokines in cell free culture supernatant was analyzed by cytokine bead array assay.Results: VA Qu Spez stimulated DCs presented with increased expression of antigen presenting molecule HLA-DR and of co-stimulatory molecules CD40, CD80 and CD86. The VA Qu Spez also induced the secretion of inflammatory cytokines IL-6 and IL-8. Further, Qu Spez-educated DC stimulated CD4+T cells in a allogeneic mixed lymphocyte reaction and activated melanoma antigen Melan-A/MART-1-specific M77-80 CD8+T cells as evidenced by increased secretion of TNF-alpha and IFNgamma.Conclusion: The VA preparations stimulate the maturation and activation of human DCs, which may facilitate anti-tumoral immune responses. These results should assist in understanding the immunostimulatory properties of VA preparations and improving the therapeutic strategies. [ABSTRACT FROM AUTHOR]