41,502 research outputs found
V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations
No full textSevere combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either of the 2 recombination activating genes (RAG)-1 and -2, which mediate the process of V(D)J recombination leading to the assembly of antigen receptor genes. It is reported here that the clinical and immunologic phenotypes of patients bearing mutations in RAGs are more diverse than previously thought and that this variability is related, in part, to the specific type of RAG mutation. By analyzing 44 such patients from 41 families, the following conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS) have missense mutations on at least one allele and maintain partial V(D)J recombination activity, which accounts for the generation of residual, oligoclonal lymphocytes; (3) in a third group of patients, findings were only partially compatible with OS, and these patients, who also carried at least one missense mutation, may be considered to have atypical SCID/OS; (4) patients with engraftment of maternal T cells as a complication of a transplacental transfusion represented a fourth group, and these patients, who often presented with a clinical phenotype mimicking OS, may be observed regardless of the type of RAG gene mutation. Analysis of the HAG genes by direct sequencing is an effective way to provide accurate diagnosis of RAG-deficient as opposed to RAG-independent V(D)J recombination defects, a distinction that cannot be made based on clinical and immunologic phenotype alone. (C) 2001 by The American Society of Hematology
Embryonic production of nitric oxide and its role in implantation: a pilot study.
No full textTo investigate the ability of human embryos to produce nitric oxide (NO) and correlate its production with embryo quality and pregnancy rate.Twenty-three women participated in the study and were submitted to controlled ovarian stimulation and intracytoplasmic sperm injection. Embryos were singularly cultured in medium microdrops of 50 microL and were replaced, by transcervical transfer, at the 2- to 6-cell stage. In the culture media of each embryo the NO production was assessed by monitoring the levels of its stable oxidation products (nitrites/nitrates).All the 23 patients underwent embryo transfer. After microinjection 64 embryos were obtained. The mean number of transferred embryos was 2.61 +/- 0.46 and the pregnancy rate was 26\%. The mean nitrite/nitrate concentrations of culture medium of each embryo was significantly higher (5.88 +/- 2.34 micromol/L) than in pure P-1 medium (0.81 +/- 0.21 micromol/L; p < 0.001) demonstrating an embryonic secretion of NO. Comparing pregnant (7.34 +/- 2.72 micromol/L) versus nonpregnant patients (5.53 +/- 1.49 micromol/L; p = 0.022), the mean nitrite/nitrate concentrations were significantly higher. Furthermore, the best quality embryos of pregnant women produced significantly higher nitrite/nitrate concentrations than those of not pregnant patients.It seems that NO production in nidating embryos is increased and that it may be primarily associated with a better morphology and a better growth potential of developing embryos
Ureteral obstruction in a patient with chronic granulomatous disease, receiving combined prophylaxis with IFN-gamma and antibiotics
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[Granulocyte disorders].
No full textThe various "in vitro" tests for evaluating polymorphonuclear leucocyte function in children with recurrent infections are described and the different clinical conditions caused or accompanied by defects in polymorphonuclear function are summarized briefly. The necessity of correct interpretation of the results of the laboratory tests used in the diagnostic evaluation of patients with suspected immunodeficiency is stressed
Immunodeficiency with hyper-IgM (HIM).
No full textImmunodeficiency with hyper-IgM (HIM) is a rare disorder characterized by recurrent infections associated with low IgG and IgA, and normal to increased IgM serum levels. Both primary and secondary forms of HIM syndrome have been reported. Among primary HIM syndrome, evidence for genetic heterogeneity is provided by the occurrence of the disease as X-linked, autosomal recessive, or autosomal dominant trait. The most common clinical manifestations include upper and lower respiratory tract infections, otitis, diarrhoea, oral ulcers, lymphoid hyperplasia, and autoimmunity. Recurrent neutropaenia is a frequent finding. Immunological abnormalities consist of lack of IgG and IgA secretion, and failure to respond to vaccination. Lymph nodes show absence of germinal centres. Few patients with a concurrent T-cell defect, and clinical expression of combined immune deficiency, have been reported. The gene responsible for the X-linked HIM syndrome (HIGM1) has been tentatively assigned to Xq24-27. However, carrier detection and prenatal diagnosis are not yet possible. Pathogenetic hypotheses include failure of B-cell differentiation, and defective regulation of immunoglobulin isotype switching due to abnormal T-cell-mediated signals. Treatment is mainly based upon regular administration of intravenous immunoglobulins. Steroids may be useful in the treatment of neutropaenia and of severe autoimmune manifestations
COVID-19 and Inborn Errors of Immunity
No full textInborn errors of immunity (IEI) are a heterogeneous group of disorders affecting immune host defense and immunoregulation. Considering the predisposition to develop severe and chronic infections, it is crucial to understand the clinical evolution of COVID-19 in IEI patients. This review analyzes clinical outcomes following SARS-CoV-2 infection, as well as response to COVID-19 vaccines in patients with IEI
Congenital and acquired defects of immunity: An ever-evolving story
No full textInborn errors of immunity (IEI), also referred to as primary immunodeficiencies (PID), are disorders that, for the most part, result from mutations in genes involved in immune host defense and immune regulation. With the increased availability of high-throughput DNA sequencing and improved genomic data interpretation, the number of newly identified genes associated with IEI has exponentially increased over the last decade. Here, we focus on the newly described IEI associated with severe COVID-19 and SASH3 deficiency, the most recently reported IEI with impaired T-cell receptor (TCR) signaling
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