Differential Effects of X-Irradiation and Cyclosporin-A Administration on the Thymus with Respect to the Generation of Cyclosporin-A-Induced Autoimmunity

Cyclosporin A (CsA), a potent inhibitor of T-cell activation, has been shown to have several effects on thymocyte maturation, thymic stromal cells, and the generation of autoreactive T cells. In Lewis rats, the combination of lethal irradiation, syngeneic bone marrow transplantation, and a 4-week course of CsA administration causes the development of an autoimmune disease (CsA-AI) resembling allogeneic graft-versus-host disease. This occurs upon withdrawal of CsA, provided the thymus receives irradiation and is present during CsA treatment. In this study, the separate effects of irradiation or CsA treatment on thymic stromal cells and thymocytes, compared to the combinatory effects, were examined using immunohistochemistry and tricolor flow cytometric analysis

Nature versus nurture in the spectrum of rheumatic diseases: Classification of spondyloarthritis as autoimmune or autoinflammatory

Abstract Spondyloarthritides (SpA) include inflammatory joint diseases with various clinical phenotypes that may also include the axial skeleton and/or entheses. SpA include psoriatic arthritis, reactive arthritis, enteropathic arthritis and ankylosing spondylitis; the latter is frequently associated with extra-articular manifestations, such as uveitis, psoriasis, and inflammatory bowel disease. SpA are associated with the HLA-B27 allele and recognize T cells as key pathogenetic players. In contrast to other rheumatic diseases, SpA affect women and men equally and are not associated with detectable serum autoantibodies. In addition, but opposite to rheumatoid arthritis, SpA are responsive to treatment regimens including IL-23 or IL-17-targeting biologics, yet are virtually unresponsive to steroid treatment. Based on these differences with prototypical autoimmune diseases, such as rheumatoid arthritis or connective tissue diseases, SpA may be better classified among autoinflammatory diseases, with a predominant innate immunity involvement. This would rank SpA closer to gouty arthritis and periodic fevers in the spectrum of rheumatic diseases, as opposed to autoimmune-predominant diseases. We herein provide available literature on risk factors associated with SpA in support of this hypothesis with a specific focus on genetic and environmental factors

The search for an autoimmune origin of psychotic disorders: prevalence of autoantibodies against hippocampus antigens, glutamic acid decarboxylase and nuclear antigens

The etiology of psychotic disorders is still unknown, but in a subgroup of patients symptoms might be caused by an autoimmune reaction. In this study, we tested patterns of autoimmune reactivity against potentially novel hippocampal antigens. Serum of a cohort of 621 individuals with psychotic disorders and 257 controls were first tested for reactivity on neuropil of rat brain sections. Brain reactive sera (67 diseased, 27 healthy) were further tested for antibody binding to glutamic acid decarboxylase (GAD) isotype 65 and 67 by cell-based assay (CBA). A sub-cohort of 199 individuals with psychotic disorders and 152 controls was tested for the prevalence of anti-nuclear antibodies (ANA) on HEp2-substrate as well as for reactivity to double-stranded DNA, ribosomal P (RPP), and cardiolipin (CL). Incubation of rat brain with serum resulted in unidentified hippocampal binding patterns in both diseased and control groups. Upon screening with GAD CBA, one of these patterns was identified as GAD65 in one individual with schizophrenia and also in one healthy individual. Two diseased and two healthy individuals had low antibody levels targeting GAD67 by CBA. Antibody reactivity on HEp-2-substrate was increased in patients with schizoaffective disorder, but only in 3 patients did antibody testing hint at a possible diagnosis of systemic lupus erythematosus. Although reactivity of serum to intracellular antigens might be increased in patients with psychotic disorder, no specific targets could be identified. GAD antibodies are very rare and do not seem increased in serum of patients with psychotic disorders.HEALTH-F2-2010-241909info:eu-repo/semantics/publishedVersio

B cell depletion in infants after intra uterine exposure to immunomodulating chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP): A case series and review of the literature

The immunomodulating chemotherapeutic drugs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) have the ablity to pass the placenta during pregnancy and might affect the development of the immune system of exposed infants. In particular rituximab causes a transient and almost complete depletion of CD20 expressing B cells and can remain detectable in the infant several months after birth.In this case series we report on the clinical and immunological outcomes of 3 infants exposed to R-CHOP during pregnancy because of maternal B-cell lymphoma and review other cases that have been published. We show that R-CHOP in pregnancy has a profound effect on the immune system in the first year of life, including B-cell lymphopenia, hypogammaglobinemia, neutropenia and decreased response to immunization. Immune monitoring of exposed infants is warranted