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)

In Africa the AIDS epidemic is primarily spread by heterosexual sexual contact. According to WHO estimates 400,000 Africans contracted AIDS in the last 10 years and approximately 3,500,000 equally divided among both sexes are infected with HIV (human immunodeficiency virus). About 600,000 of them are children 5. Child mortality is projected to increase by 50% in the next 10 years attributable to a further spread of HIV among women who will contaminate their children. Currently, there are more than 1 million African children 10 who are not infected but whose mothers are. There are ominous implications both for women in the traditional role and for working African women on the infrastructure in addition to the anxiety of contracting HIV, the impact on future pregnancies, and the stigma of AIDS victims who are ostracized from society. The case of a woman whose husband recently died of AIDS and who is suffering from ARC (AID-related complex) is detailed. Her twin daughters aged almost 2 are also seropositive. At a clinic an AIDS worker informed her that she and her daughters had 1 or 2 more years to live. AIDS has placed a double burden on the shoulders of African women: to prevent AIDS as care providers and to help the victims, especially because governments and organizations do not provide much support. Committed women who organize to overcome social injustice intrinsic in the suffering of AIDS victims can develop the fighting spirit to better their lives.
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PMID:[The consequences of AIDS for women and children in Africa]. 206 27

Case management has become an important strategy in responding to the complex physical and social needs of persons with human immunodeficiency virus (HIV) disease. Yet, inconsistent implementation and professional turf guarding, based on disciplinary differences, have rendered traditional models ineffective. AID Atlanta has adopted an integrated, multisite approach to case management that uses the expertise of social workers, nurses, pastoral counselors, and therapists to develop client-centered plans of care across the continuum of need. This article presents the integrated model and describes the standards of service and outcome evaluation criteria that underpin this model. The impact of nursing expertise on the development of the model is discussed.
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PMID:An integrated case management model: developing standards, evaluation, and outcome criteria. 815 32

Recent studies have shown that mutations in a newly described RNA editing enzyme, activation-induced cytidine deaminase (AID), can cause an autosomal recessive form of hyper IgM syndrome. To determine the relative frequency of mutations in AID, we evaluated a group of 27 patients with hyper IgM syndrome who did not have defects in CD40 ligand and 23 patients with common variable immunodeficiency. Three different mutations in AID were identified in 18 patients with hyper IgM syndrome, including 14 French Canadians, 2 Lumbee Indians, and a brother and sister from Okinawa. No mutations were found in the remaining 32 patients. In the group of patients with hyper IgM syndrome, the patients with mutations in AID were older at the age of diagnosis, were more likely to have positive isohemagglutinins, and were less likely to have anemia, neutropenia, or thrombocytopenia. Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the patients with hyper IgM syndrome and defects in AID.
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PMID:Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome. 1111 57

The hyper IgM syndrome is a rare, inherited immune deficiency disorder resulting from defects in the CD40 ligand/CD40-signaling pathway. X-linked hyper IgM is caused by defects in the CD40 ligand gene, while autosomal recessive hyper IgM is caused by defects in the CD40-activated RNA-editing enzyme, activation-induced cytidine deaminase, which is required for immunoglobulin isotype switching and somatic hypermutation in B cells. The loss of interaction between CD40 and its ligand in X-linked hyper IgM results in an impairment of T cell function, of B cell differentiation, and of monocyte function, while only B cell differentiation appears to be affected in autosomal recessive hyper IgM. With genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitely, to perform genetic screening, and to delineate the clinical manifestations of this syndrome. Further research may lead to novel and definitive therapeutic options for patients with hyper IgM syndrome.
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PMID:The hyper IgM syndrome. 1189 71

In humans several abnormalities can occur during terminal B cell differentiation, leading to primary humoral immunodeficiencies. A recent study provided evidence of a qualitative defect of the affinity antibody maturation in some patients affected with common variable immunodeficiency syndrome, the molecular basis of which remains unknown. Several genetic defects in class switch recombination leading to a hyper-IgM syndrome have recently been delineated. Besides the well-known role of CD40-CD40 ligand interaction, they definitively demonstrate the requirement of CD40-mediated nuclear factor kappa B activation and the essential role of a newly described molecule, the activation-induced cytidine deaminase, in B cell terminal differentiation.
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PMID:Terminal defects of B lymphocyte differentiation. 1196 35

The deamination of cytosines in DNA to uracil, thought to be initiated by free water within the cells, is a well studied pathway by which C to T mutations occur. Until recently, this conversion was frequently referred to as being spontaneous because of the involvement of cellular water. The recent discovery of a family of enzymes in mammalian cells that catalyze this reaction was unexpected and has created excitement in at least two areas of biology, immunology and virology. One of these enzymes, activation-induced cytidine deaminase (AID), is required for the final steps in the maturation of antibodies. The key features of this process include the introduction of a wide variety of base substitutions in the immunoglobulin genes and the creation of region-specific double-strand breaks. Another member of this family, Apobec3G, is involved in the mutational inactivation and degradation of the human immunodeficiency virus (HIV-1). Among the many intriguing features of these processes is the likely involvement of the enzyme that is thought to "protect" cellular DNA against the accumulation of uracils, uracil-DNA glycosylase (UDG). It appears that in certain situations, the newly discovered DNA-cytosine deaminases can team up with UDG to extensively mutate and degrade DNA. This article discusses the many questions raised regarding the role of these enzymes in protecting cells against infections, and about their possible roles in genome evolution and carcinogenesis.
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PMID:DNA-cytosine deaminases: from antibody maturation to antiviral defense. 1517 77

Ligation of CD40 by CD4 T cells through CD154 is key both to germinal centre induction and follicular T-dependent Ig class switching, but its requirement for aspects of T cell priming and extrafollicular antibody responses is less clear. Here comparison of the T helper (Th) type 2 response in lymph nodes from wild-type mice and CD154-deficient mice after immunization with alum-precipitated antigen reveals selective effects of this immunodeficiency. The timing and magnitude of the early interleukin (IL)-4 induction and proliferation in T cells of the T zone were unaltered by CD154 deficiency. As expected, germinal centres were not induced. Additionally the T-dependent extrafollicular antibody response, which initially requires T cell help but expands without further T cell involvement, was severely curtailed. The median number of extrafollicular antigen-specific plasma cells was 370-fold lower in CD154-deficient mice. Of these plasma cells the median proportion that had switched to IgG1 was <5%, while in wild-type mice the proportion was 89%. Surprisingly, some CD154-deficient lymph nodes showed substantial switching to IgG1. Commensurately, increases in gamma1 germline transcripts and Blimp-1 mRNA were observed, albeit significantly lower than in controls, but activation-induced cytidine deaminase mRNA was undetectable in CD154-deficient mice. These experiments demonstrate that the acquisition of some T cell priming characteristics can be CD154-independent; in contrast, T-dependent extrafollicular responses require CD154. Thus functional CD154 ligation during the first encounter of T cells and B cells in the T zone is critical for follicular and extrafollicular antibody responses.
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PMID:Loss of CD154 impairs the Th2 extrafollicular plasma cell response but not early T cell proliferation and interleukin-4 induction. 1537 79

A functional immune system is one of the prerequisites for the survival of a species. Humans have one of the most complicated immune systems, with the ability to learn from and adapt to pathogens. At first, a primary repertoire of antibodies is generated, which, upon antigen encounter, will diversify and adapt to produce a highly specific and potent secondary response, part of which is kept in memory to fight off future infections. In this review, the mechanism as well as the specificities of the key protein in the secondary immune response, activation-induced cytidine deaminase (AID), are highlighted, as well as its role in the DNA deamination model of immunoglobulin diversification. The review also highlights aspects of AID's regulation on both the transcriptional as well as post-translational level and its potential molecular mechanism and specificity. Furthermore, it expands outside the involvement of AID in somatic hypermutation, class switching, and gene conversion to discuss the implications of DNA deamination in epigenetic modifications of DNA (as a potential demethylase), the induction of mutations during oncogenesis, and includes an evolutionary comparison to the DNA deaminase family member APOBEC3G, a key protein in human immunodeficiency virus pathogenesis.
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PMID:DNA deamination in immunity. 1566 Oct 23

The activation-induced deaminase/apolipoprotein B-editing catalytic subunit 1 (AID/APOBEC) family comprises four groups of proteins. Both AID, a lymphoid-specific DNA deaminase that triggers antibody diversification, and APOBEC2 (function unknown) are found in all vertebrates examined. In contrast, APOBEC1, an RNA-editing enzyme in gastrointestinal cells, and APOBEC3 are restricted to mammals. The function of most APOBEC3s, of which there are seven in human but one in mouse, is unknown, although several human APOBEC3s act as host restriction factors that deaminate human immunodeficiency virus type 1 replication intermediates. A more primitive function of APOBEC3s in protecting against the transposition of endogenous retroelements has, however, been proposed. Here, we focus on mouse APOBEC2 (a muscle-specific protein for which we find no evidence of a deaminating activity on cytidine whether as a free nucleotide or in DNA) and mouse APOBEC3 (a DNA deaminase which we find widely expressed but most abundant in lymphoid tissue). Gene-targeting experiments reveal that both APOBEC2 (despite being an ancestral member of the family with no obvious redundancy in muscle) and APOBEC3 (despite its proposed role in restricting endogenous retrotransposition) are inessential for mouse development, survival, or fertility.
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PMID:Mice deficient in APOBEC2 and APOBEC3. 1605 35

The immune system is the site of various genotoxic stresses that occur during its maturation as well as during immune responses. These DNA lesions/modifications are primarily the consequences of specific physiological processes such as the V(D)J recombination, the immunoglobulin class switch recombination (CSR), and the generation of somatic hypermutations (SHMs) within Ig variable domains. The DNA lesions can be introduced either by specific factors (RAG1 and RAG2 in the case of V(D)J recombination and AID in the case of CSR and SHM) or during the various phases of cellular proliferation and cellular activation. All these DNA lesions are taken care of by the diverse DNA repair machineries of the cell. Several animal models as well as human conditions have established the critical importance of these DNA lesions/modifications and their repair in the physiology of the immune system. Indeed their defects have consequences ranging from immune deficiency to development of immune malignancy. The survey of human pathology has been highly instrumental in the past in identifying key factors involved in the generation of DNA modifications (AID for the Ig CSR and generation of SHM) or the repair of specific DNA damages (Artemis for V(D)J recombination). Defects in factors involved in the cell cycle checkpoints following DNA damage also have deleterious consequences on the immune system. The continuous survey of human diseases characterized by primary immunodeficiency associated with increased sensitivity to ionizing radiation should help identify other important DNA repair factors essential for the development and maintenance of the immune system.
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PMID:The repair of DNA damages/modifications during the maturation of the immune system: lessons from human primary immunodeficiency disorders and animal models. 1610 76


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