Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral pulmonary infections are a major cause of morbidity and mortality in solid organ transplant recipients. The herpes viruses-cytomegalovirus, herpes simplex virus, varicella zoster virus, and Epstein-Barr virus--cause most of the viral infections in this population. Respiratory syncytial virus, adenovirus, and human immunodeficiency virus also cause pneumonitis in the transplant recipient. Differences in the clinical and laboratory presentation of pneumonitis due to the various viral agents can provide clues to the etiology. However, definitive diagnosis requires laboratory identification of the virus or appropriate serologic changes. With cytomegalovirus, herpes simplex virus, Epstein-Barr virus, and adenovirus, one must take care to distinguish between asymptomatic shedding of the virus and disease produced by the virus. Advances in diagnostic techniques such as rapid antigen detection, nucleic acid hybridization, and gene amplification may allow an earlier diagnosis of viral pneumonia. Advances in risk reduction with appropriate pairing of donors and recipients, improved immunosuppressive regimens, vaccination, and prophylactic administration of antiviral agents may reduce the incidence of viral infection. Finally, advances in anti-viral therapy have made possible the successful treatment of pneumonia due to some of the viral agents.
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PMID:Viral pneumonia in recipients of solid organ transplants. 216 Jul 18

A selective CD3 gamma defect, involving point mutations in both the paternal and the maternal genes, has been analyzed. The CD3 gamma defect affected two brothers of a four sibs family; one of them died at the age of 3 of a viral pneumonia with concomitant autoimmune features (Haemolytic anaemia and gut epithelial cell autoantibodies), whereas the other is still alive at the age of 10 with relatively mild infection episodes. In this work, the effects of the absence of the CD3 gamma chain in the structure and signal transduction of the T-cell receptor (TCR)/CD3 complex and in the selection and function of T lymphocytes were studied. The absence of CD3 gamma did not prevent the expression of certain amounts of TCR/CD3 complexes on the surface of T lymphocytes. This suggests the existence of at least two TCR/CD3 isoforms in T cells, either with or without CD3 gamma. A persistent low proportion of CD8+ T cells, not functional in vitro (they were unable to proliferate) and probably in vivo (associated to a lethal viral pneumonia), was observed. In contrast, the proportion of CD4+ T cells was not altered, and they were functional both in vitro (they showed a normal proliferation and a low, but detectable, increase of cytosolic Ca2+ in response to anti-TCR/CD3 stimuli, although the production of IL-2 was impaired) and in vitro (they normally helped B cells). These results show that the absence of CD3 gamma affects the selection and function of cytotoxic, but apparently not helper, T lymphocytes, although the possibility that the CD4+ T cells represent a specific subpopulation can not be ruled out. They also suggest that the interactions of the TCR/CD3 complex with its co-receptors during thymic selection and antigen recognition in the periphery may be asymmetrical, with CD8 interacting through CD3 gamma and, probably, CD4 through the homologous CD3 delta.
Immunodeficiency 1993
PMID:T lymphocyte signalling defects and immunodeficiency due to the lack of CD3 gamma. 790 75

Respiratory viruses are a common cause of morbidity in childhood. Except in the child with immunodeficiency, the common respiratory viruses rarely pose a serious threat to life. Because infection with most of these viruses in childhood is nearly universal and usually bestows partial immunity, the "childhood respiratory viruses" are not generally thought of as being a cause of disease in adults. However, adults who work around children, who are frequently exposed to other adults and children with respiratory tract infections (as in a hospital clinic setting), or who are military recruits appear to be at risk of infection or reinfection with one of these agents. In addition, adults with immune deficiency are at a significant risk for serious infection. The risk of serious disease can be reduced by maximizing immunity with (re)immunization and optimal treatment of any underlying disorders. Tobacco smoke and respiratory irritants should be avoided and adults at risk for severe disease should avoid contact with infected children and adults as much as possible. Specific chemotherapy for viral pneumonia, when available, may reduce morbidity in selected individuals.
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PMID:"Childhood" viruses as a cause of pneumonia in adults. 866 51

The diagnosis and management of human immunodeficiency virus (HIV) infected infants and children who do not respond to recommended empiric therapy for acute or chronic pneumonia is a frequent clinical challenge, especially as the greatest burden of childhood HIV-related lung disease occurs in low-income regions where options for investigation and treatment are limited. Lung disease is due to a wider spectrum of causes in HIV-infected than non-infected children. Bacterial pneumonia, viral pneumonia and pulmonary tuberculosis (TB) are common in children throughout the developing world, and the added impact of HIV infection on the incidence and outcome of these diseases is covered in companion articles. This review focuses on lung diseases that are more specifically HIV-related. Pneumocystis jirovecii pneumonia (PJP) is a major cause of pneumonia and death in HIV-infected infants, especially in regions where maternal HIV status is often not known and the provision of PJP prophylaxis for HIV-exposed infants is unusual. Cytomegalovirus is commonly found in the lungs of HIV-infected infants, with implications for the use of corticosteroids for PJP. Lymphoid interstitial pneumonitis, a common cause of persistent respiratory symptoms in HIV-infected children, must be differentiated from pulmonary or miliary TB. The incidence of uncommon causes such as fungal pneumonia or HIV-related pulmonary malignancy varies among regions. The burden of lung disease due to opportunistic infections would be significantly reduced by more widely applying available measures that reduce mother-to-child HIV transmission, by providing cotrimoxazole prophylaxis for HIV-exposed infants, and by increasing the availability of antiretroviral therapy.
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PMID:Non-tuberculosis opportunistic infections and other lung diseases in HIV-infected infants and children. 1597 85

Influenza virus infection is a seasonal infectious disease for humans, whereas it is also a zoonosis that is originally transmitted from animals to humans. Therefore, several animal models are used in research on influenza virus infection. We have used a nonhuman primate (NHP) model to extrapolate pathogenicity of various influenza viruses and efficacy of vaccines and antiviral drugs against the influenza viruses in humans. NHPs have genes, anatomical structure, and immune responses similar to those of humans as compared to other animal models. Using an NHP model, we revealed that the pandemic 2009 influenza A virus caused viral pneumonia as reported in human patients. Thus, it is thought that NHP models can be used to predict replication of emerging viruses in humans. We also examined the pathogenicity of highly pathogenic avian influenza viruses and evaluated a new therapeutic antibody in macaques under an immunocompromised condition. NHP models have provided promising results in research on other infectious diseases including Ebola virus and human/simian immunodeficiency virus infections. Thus, NHPs are important in biomedical research for determining the pathogenesis and for development of treatments, especially when clinical trials are difficult. We summarize the characteristics and advantages of research using NHP models in this review.
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PMID:Translational research on influenza virus infection using a nonhuman primate model. 2681 Nov 9

The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood.
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PMID:Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease. 2742 83

The T-cell receptor (TCR)/CD3 complex is crucial for T-cell development and regulation. In humans, CD3D, CD3E, and CD3Z gene defects cause severe combined T- and B-cell immunodeficiency. However, CD3G mutations alone lead to a less severe condition, which is mainly characterized by autoimmunity. In the present study, we report the case of a 36-year-old male who presented with recurrent sinopulmonary infections without opportunistic infections; this was compatible with hypogammaglobulinemia, but normal PHA-lymphocyte proliferation. This patient had the common variable immunodeficiency (CVID) phenotype and received regular immunoglobulin infusions over 20-years; he gradually developed nodular regenerative hyperplasia over a 5-year period. Distinct from the previously reported CD3G mutations, which mainly present as autoimmunity, the novel CD3G deletion (c.del213A) in our patient caused an obvious decrease in switched memory B cells and diminished CD40L expression. However, sufficient Treg suppression function was maintained so that he remained free of autoimmune thyroiditis (AIT), inflammatory bowel disease (IBD), and autoimmune pancytopenia. A PubMed search for this rare disease entity revealed seven Turkish and two Spanish patients (five unrelated families). Among a total of 20 alleles, there were 14 splicing mutations (80(-1)G>C), two missense mutations (c.1G>A), two nonsense mutations (c.250A>T), and two deletions (c.del213A). Three patients presented with isolated AIT without significant infections. Three patients died, one from a severe infection at 31 months, one from post-transplant respiratory failure due to viral pneumonia at 17 months, and one from graft-vs.-host disease at 47 months. Those experiencing opportunistic infections, severe life-threatening infections in need of hematopoietic stem cell transplantation, and IBD-like diarrhea had a significantly higher mortality rate compared with those without these features (p = 0.0124, p = 0.01, and p = 0.0124, respectively). The patients with AIT had a significantly better prognosis (p = 0.0124) to those without AIT. Our patient with the novel CD3G mutation presented with predominant B-cell deficiency overlapping with the CVID phenotype but without recognizable autoimmunity, which was consistent with his normal Treg suppression function.
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PMID:A Novel CD3G Mutation in a Taiwanese Patient With Normal T Regulatory Function Presenting With the CVID Phenotype Free of Autoimmunity-Analysis of all Genotypes and Phenotypes. 3192 Nov 17

X-linked agammaglobulinemia (XLA) is a primary humoral immunodeficiency characterized by severe hypogammaglobulinemia and increased risk of infection. The genetic condition results from a mutation in the Bruton tyrosine kinase (BTK) gene located on the X chromosome leading to a near absence of B cells. Patients affected by XLA are most commonly predisposed to frequent and severe bacterial infections. However, here we report the case of a 20-year-old male with XLA who presented with viral pneumonia with multiple pathogens. This coexistence has been rarely reported. The patient received intravenous immunoglobulin therapy with noted significant improvement in the two weeks of follow-up. His clinical history supports the hypothesis of increased susceptibility to viral pathogens in the absence of immunoglobulin therapy. The humoral defect is the cornerstone of this phenomenon. This case presents the importance of multiviral causes for patients with recurrent episodes of pneumonia in an immunocompromised state.
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PMID:X-linked Agammaglobulinemia Presenting with Multiviral Pneumonia. 3248 38

Immunocompromised patients, including HSCT recipients, may have a poor prognosis after contracting COVID-19 due to the absence of a pathogen-specific adaptive immune response. One of the possible options for severe COVID-19 treatment may be the transfusion of hyperimmune SARS-CoV-2 convalescent plasma. A 9-month-old girl with juvenile myelomonocytic leukemia received an HSCT from a haploidentical donor. On day +99, during routine virologic monitoring, SARS-CoV-2 was detected without any clinical symptoms. On day +144, the child developed a polysegmental bilateral viral pneumonia with 60 % damage to the lung tissue and confirm a positive SARS-Cov-2 results in throat swab. The patient was treated with tocilizumab and three doses of fresh frozen plasma obtained from a SARS-CoV-2 convalescent patient. Therapy with tocilizumab and three doses of fresh frozen plasma was well tolerated. In spite of full resolution of the lung lesions, complete elimination of SARS-CoV-2 has not been achieved 4 months after the first detection, which is due to persistence of secondary immunodeficiency after HSCT and the lack of reconstitution of the adaptive immune response. This case represents a demonstration of an atypical course of COVID-19 and the delayed development of lung lesions, which was most likely associated with the features of the patient's immune status after HSCT. SARS-CoV-2 convalescent plasma in combination with other therapeutic approaches is one of the possible curative options for this clinical situation.
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PMID:SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation. 3315 2