Immunodeficiency reviews最新文献

{"title":"Immunodeficiency with hyper-IgM (HIM).","authors":"L D Notarangelo,&nbsp;M Duse,&nbsp;A G Ugazio","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Immunodeficiency 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.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 2","pages":"101-21"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12722961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B and T cell leakiness in the scid mouse mutant.","authors":"M J Bosma","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recombination of antigen receptor gene elements (V, D and J) that code for Ig and TCR variable regions is defective in the scid mouse mutant. However, the defect is not absolute. Developing scid lymphocytes occasionally succeed in forming a productive VDJ and VJ rearrangement at two critical loci (e.g., IgH/IgL or TCR beta/TCR alpha), and given the appropriate stimuli, differentiate into clones of functional B or T cells. Scid mice with detectable B and/or T lymphocytes are referred to as leaky. This review considers the nature and possible basis of B and T cell leakiness in scid mice.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 4","pages":"261-76"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis.","authors":"M P Lefranc,&nbsp;L Hammarström,&nbsp;C I Smith,&nbsp;G Lefranc","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Single and extensive multigene deletions have been described in the Ig CH immunoglobulin heavy-chain constant region genes, some of these encompassing up to 160 kilobases. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their findings; deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP-G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly in the Mediterranean area. The high level of consanguinity in the Tunisian population accounts for the high frequency of individuals homozygous for one or the other of these multigene deletions which involve highly homologous regions as hot spots of recombinations, outside of the switch sequences, in the Ig CH locus. In 15 cases out of 16, these multigene deletions have been observed in healthy people, although these individuals lacked several immunoglobulin subclasses and, even, one class. Such an immunological situation makes it possible to study the importance of these subclasses for the overall immunity, and to analyse the specific immune responses by the retained IgG and IgA subclasses.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"2 4","pages":"265-81"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13064982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Xlr (X-linked lymphocyte regulated) gene family (a candidate locus for an X-linked primary immune deficiency).","authors":"H J Garchon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The murine Xlr (X-chromosome linked lymphocyte-regulated) gene family was originally identified by subtractive cDNA cloning and hybridization. A single predominant functional transcript encoding a 25 kDa peptide was initially found to be expressed in lymphoid cell lines corresponding to late stages of differentiation. A second functional Xlr gene has now been defined. It is expressed in differentiating male germ cells. Both the lymphoid and the germinal cell Xlr proteins are located in the cell nucleus and are closely homologous to each other. In parallel with the small number of currently known functional transcripts, the Xlr family comprises 50-75 sequences per haploid genome of which a majority is nonfunctional and that are localized on the proximal half of the X-chromosome and also on the Y-chromosome. This accumulation of pseudogenes may be related to the evolutionarily recent amplification of Xlr in rodents. Although murine Xlr probes do not cross-hybridize with human DNA, the existence of a human homolog for Xlr should be nevertheless postulated because of the conservation of X-chromosomal organization in mammals. Possible relationships of Xlr with X-linked primary immune deficiencies in man and mouse are finally discussed.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"2 4","pages":"283-302"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13215477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early therapeutic intervention in HIV infection--stepping stones to success.","authors":"I V Weller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The improvement in survival observed in symptomatic HIV disease in the last three years may be accounted for by factors over and above the introduction of zidovudine therapy. Such factors include earlier diagnosis and advances in the treatment and prophylaxis of life threatening opportunistic infections. These advances in the management of symptomatic HIV disease considerably influenced the move towards early intervention in asymptomatic infected individuals. Currently two developments are changing clinical practice, namely the primary prophylaxis of pneumocystis carinii pneumonia and antiretroviral treatment with zidovudine. This review concerns itself with the scientific data supporting such changes in practice and the uncertainties and unanswered questions that remain, particularly with respect to the timing of intervention with and appropriate dose of zidovudine.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"2 4","pages":"303-13"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13215478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purine nucleoside phosphorylase deficiency.","authors":"M L Markert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disease accounting for approximately 4% of patients with severe combined immunodeficiency. Thirty-three patients have been reported. PNP-deficient patients suffer from recurrent infections, usually beginning in the first year of life. Two thirds of patients have evidence of neurologic disorders. Findings range from spasticity to developmental delay, to mental retardation. One third of patients develop autoimmune disease. The most common manifestation of this is autoimmune hemolytic anemia. Idiopathic thrombocytopenic purpura and systemic lupus erythematosis have also been reported. Patients usually present with infections but approximately one fourth have come to medical care initially for neurological problems. In PNP deficiency, T- and B-cell immunity are affected. T-cell function may be profoundly deficient, may be normal at birth and then decrease with time, or may fluctuate repeatedly between low and normal. B-cell function can be normal but is deficient in approximately one third of patients. PNP protein is a trimer of approximately 90,000 daltons. It is found in most tissues of the body but is at highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. Many mechanisms have been proposed to explain the metabolic toxicity in PNP deficiency. The elevated dGTP found in PNP deficiency is thought to inhibit ribonucleotide reductase and, thus, impede cell division. Depressed GTP levels may correlate with neurologic dysfunction. The gene for PNP has been cloned; it is located on the long arm of chromosome 14. Studies of a mutant PNP gene isolated from one patient showed that a point mutation resulting in an amino acid substitution was responsible for PNP deficiency. PNP deficiency has a grave prognosis. No patient has reached the third decade of life. Twenty-nine of the 33 reported patients have died from their disease. Prenatal diagnosis is currently available. Many different therapies have been utilized for PNP deficiency including bone marrow transplantation, red cell transfusions, and supplementation of the diet with purines and pyrimidines. None of these therapies has been consistently successful. In light of the poor prognosis for PNP deficiency, bone marrow transplantation should be considered for all patients. In the future, improved forms of therapy such as gene therapy may become available.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 1","pages":"45-81"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13091076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgA deficiency.","authors":"F M Schaffer,&nbsp;R C Monteiro,&nbsp;J E Volanakis,&nbsp;M D Cooper","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>IgA deficiency, the most common primary immunodeficiency, is a very heterogeneous clinical disorder which may be associated with a variety of infections, allergies, autoimmune disorders, gastrointestinal diseases, and genetic disorders. The central phenotypic feature of this immunodeficiency is a B cell differentiation arrest, the extent of which may determine the clinical variability. Integrity of the immunoglobulin genes and their expression by immature B cells in affected individuals suggests an immunoregulatory basis for the B cell arrest. Genetic studies imply that a susceptibility gene in or near the major histocompatibility locus may predispose homozygous individuals to a spectrum of antibody deficiencies which may range from isolated IgA deficiency to panhypogammaglobulinemia. Essential cofactors in the pathogenesis of IgA deficiency include environmental factors, such as certain drugs and viral infections.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 1","pages":"15-44"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13091075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human graft-versus-host disease.","authors":"R Parkman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The principal clinical problem encountered following allogeneic bone marrow transplantation is acute and chronic graft-versus-host disease. The presence of acute graft-versus-host disease is the strongest predictor for the development of chronic graft-versus-host disease. The introduction of new prophylactic regimens has reduced the incidence of acute graft-versus-host disease. The clinical presentation and pathophysiology of acute and chronic graft-versus-host disease are discussed. New therapies for chronic graft-versus-host disease may result in improved treatment for human autoimmune diseases.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"2 4","pages":"253-64"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13215476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AZT resistance in isolates of HIV.","authors":"D D Richman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The development of reduced susceptibility to zidovudine (AZT) has been documented in isolates of human immunodeficiency virus (HIV) from patients receiving prolonged therapy with the drug. Resistance emerges more quickly and to a higher degree in patients in later stages of disease. Progressive stepwise reductions in susceptibility occur with sequential isolates in conjunction with the cumulative acquisition of mutations in the gene for reverse transcriptase. Cross resistance to other compounds has been observed to date only with nucleosides possessing a 3'-azido moiety. The clinical significance of reduced drug susceptibility and strategies to deal with this issue are under investigation.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"2 4","pages":"315-8"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13214828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DiGeorge anomaly.","authors":"R Hong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The DiGeorge anomaly, DGA (formerly termed DiGeorge syndrome), is now known to be a developmental field defect in which pharyngeal pouch derivatives do not arise, usually because of inadequate neural crest contributions. The conditions in which this occurs include exposure to teratogens, cytogenetic abnormalities, and Mendelian disorders. As a result, the facies and cardiovascular defects which occur are very characteristic. Two rare conotruncal anomalies, type B interrupted aortic arch and truncus arteriosus account for over half of the cardiac lesions seen in DGA. Failure of descent of the thymus is extremely common in DGA, but immunodeficiency which requires correction occurs only in approximately 25% of the cases. The term, complete DGA, should be reserved for those patients in need of reconstitution of the immune system. One can identify those patients requiring treatment of the thymic defect by T cell enumeration and in vitro proliferation assays. Two alternatives for therapy are thymus transplantation and bone marrow transplantation from a HLA matched sibling.</p>","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13089034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}