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Results for “inborn errors of immunity”

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At least 73 records · Page 4Linked to original sources
PubMed1974

Human beta-D-N-acetylhexosaminidases A and B: expression and linkage relationships in somatic cell hybrids.

Knowledge of the genetic relationships between beta-D-N-acetylhexosaminidases A and B (EC 3.2.1.30) may help in understanding the hexosaminidase deficiency associated with GM(2) gangliosidosis, a fatal lipid storage disease in man. Through the use of man-mouse somatic cell hybrids we have found that a gene involved in hexosaminidase A expression was linked to the genes coding for mannosephosphate isomerase and pyruvate kinase-3. The gene coding for hexosaminidase B was not linked to any of the genes coding for 25 enzyme markers tested. A combination of immunological and electrophoretic techniques was employed to identify human hexosaminidases A and B with certainty in cell hybrids. Discordant segregation of hexosaminidase A and hexosaminidase B in 60 clones indicated that the genes coding for their expression were not linked. However, hexosaminidase A was never expressed in cell hybrids in the absence of hexosaminidase B. This suggests that the gene responsible for the hexosaminidase A phenotype, linked to mannosephosphate isomerase and pyruvate kinase-3, requires the presence of the gene coding for hexosaminidase B for the expression of hexosaminidase A. These observations offer a genetic explanation for the biochemical and immunological relationships between hexosaminidases A and B and provide the framework for identifying the basic genetic defects responsible for GM(2) gangliosidosis.

Animals↗
PubMed2002

Mechanisms of liver injury relevant to pediatric hepatology.

Hepatocyte injury and necrosis from many causes may result in pediatric liver disease. Influenced by other cell types in the liver, by its unique vascular arrangements, by lobular zonation, and by contributory effects of sepsis, reactive oxygen species and disordered hepatic architecture, the hepatocyte is prone to injury from exogenous toxins, from inborn errors of metabolism, from hepatotrophic viruses, and from immune mechanisms. Experimental studies on cultured hepatocytes or animal models must be interpreted with caution. Having discussed general concepts, this review describes immune mechanisms of liver injury, as seen in autoimmune hepatitis, hepatitis B and C infection, the anticonvulsant hypersensitivity syndrome, and autoimmune polyendocrinopathy. Of the monogenic disorders causing significant liver injury in childhood, alpha-1 antitrypsin deficiency and Niemann-Pick C disease demonstrate the effect of endoplasmic or endosomal retention of macromolecules. Tyrosinemia illustrates how understanding the biochemical defect leads to understanding cell injury, extrahepatic porphyric effects, oncogenesis, pharmacological intervention, and possible stem cell therapy. Pathogenesis of cirrhosis in galactosemia remains incompletely understood. In hereditary fructose intolerance, phosphate sequestration causes ATP depletion. Recent information about mitochondrial disease, NASH, disorders of glycosylation, Wilson's disease, and the progressive familial intrahepatic cholestases is discussed.

Autoimmune Diseases↗
PubMed1982

A review of some effects of recent medical practices in reducing the numbers of children born with congenital abnormalities.

Attempts to reduce the number of children born with congenital malformations may be seen as part of the programmes for rubella immunization and for screening for neural tube defects and chromosome anomalies. The rubella immunization programme in England and Wales has not been accompanied by any appreciable decline in the overall incidence of heart or eye malformations detected at or soon after birth. However, the decline in the incidence of babies born with defects of the central nervous system, and of babies born with Down's syndrome to elderly mothers, indicates that interventive methods of control are achieving changes.

Congenital Abnormalities↗
PubMed1991

[History of immunologic deficiency].

The description of agammaglobulinemia by O. Bruton in 1952 and later clinical studies by R. Good preceeded by sporadic clinical observations on deficits in the immune function associated with hyponutrition, nephrosis and tumors or with inborn errors of metabolism have all made their contribution to the emerging of the concept of immunological deficiency diseases. The clinical-pathogenetic description of immunological deficiency diseases has played a fundamental role in the understanding of the anatomo-functional bases of the immune system and research work on the phylogenetic and ontogenetic evolution of the immune response. Various methodologies, from the idea of experimentum naturae to molecular pathology, combine to define and direct this research, the result of an ongoing interaction between the hospital and the laboratory. This leads to a necessary theoretical-practical synthesis and contributes to the consolidation of an immunologically-directed medicine.

Adolescent↗
PubMed1975

Combined immunodeficiency disease: an inborn error of purine metabolism.

The recently discovered association of adenosine deaminase (ADA) deficiency and combined immune deficiency (CID) has emphasized the critical role of purine salvage in the function of lymphoid tissue. Known enzymatic properties of ADA are presented. In addition, known phenotypic data and possible genetic mechanisms for the occurrence of ADA deficiency in CID are discussed. A hypothesis based on considerations of known metabolic pathways in human erythrocytes is proposed to account for the selectivity of ADA deficiency for lymphoid tissue. Finally, some inhibitors of ADA are discussed as well as some immunosuppressive agents.

Adenine↗
PubMed1983

[Rubella immunity in pregnant women in 1983].

The measurement of diaplacentally transferred specific antibodies in 2153 samples of dried blood of our neonatal screening programme for the detection of inborn errors of metabolism showed that only 4.3% of the children's mothers lacked immunity to rubella in March 1983. This demonstrated a substantial improvement as compared with 1979 and 1982 when 9.3 and 5.3% of the mothers were susceptible to infection with the rubella virus. The reimbursement of serological testing by the legal insurance companies and the vaccination in case of negative results were considered instrumental in reducing the susceptibility to rubella.

Adolescent↗
PubMed1980

Genetically determined deficiencies in IgA and IgG.

Disturbance in the immune response can be caused by malfunction of T and/or B cells. Certain inborn errors such as absence of enzymes in the purine salvage pathway, may lead to severe combined immunodeficiencies or to other syndromes related to impaired immune response, that are mostly diseases of infancy. Selective immunodeficiencies in one or more immunoglobulin subclasses are less severe and occur among adults. The best known is IgA deficiency. The first case of IgG3 subclass deficiency was described in 1976 [13]. Examples of IgG1 and IgG2 deficiencies are reported in this paper. The implication of structural and of regulator genes in the various defects is discussed.

B-Lymphocytes↗
PubMed2006

Immunizations for patients with metabolic disorders.

Individuals with underlying metabolic disorders are a potential high-risk group for vaccine-preventable diseases. Newborn metabolic screening has provided a means of early identification and treatment for many of these disorders, whereas childhood immunization is one of the most effective means of decreasing the morbidity and mortality resulting from communicable diseases worldwide. There are very few contraindications to the routine administration of vaccines to the healthy, immunocompetent individual. In certain high-risk groups, such as immunocompromised patients, gravid females, and those with a history of previous anaphylactic reaction to a vaccine or its components, selective withholding of immunizations must be considered to decrease potential adverse events. A detailed analysis of the medical literature revealed few specific recommendations regarding appropriate immunization techniques for patients with metabolic disorders. In this review we detail the major metabolic disorder subtypes, elaborate on the available literature on immunizations for patients with these disorders, and provide suggested vaccine recommendations.

Adolescent↗
PubMed2000

Transient depletion of CD4 lymphocyte improves efficacy of repeated administration of recombinant adenovirus in the ornithine transcarbamylase deficient sparse fur mouse.

One of the current limitations of adenoviral gene therapy is a vector-induced humoral immune response that blocks effective re-administration of the vector. In an animal model of the inborn error of urea synthesis ornithine transcarbamylase (OTC) deficiency, the sparse fur (spf/y) mouse, we tested a strategy to transiently block the CD4 mediated immune response at the time of virus administration using an anti-CD4 monoclonal antibody (GK1.5). The co-administration of GK1.5 resulted in a significantly diminished production of neutralizing antibody to the adenovirus vector, but minimally prolonged metabolic correction. A second infusion of the same virus in GK1.5 treated spf/y mice led to a complete normalization of liver OTC activity at day 3 after infection and a significant metabolic correction of urinary orotate and plasma glutamine. In contrast, there was no evidence of enhanced OTC expression or metabolic correction (measured by normalization of plasma glutamine and urinary orotate) after the second infusion of virus in spf/y mice not treated with GK1.5. Furthermore, when co-administered with two consecutive doses of adenovirus, the anti-CD4 treatment allowed improved transgene expression upon a third administration of virus and a partial normalization of the metabolic abnormalities, compared with mice that did not receive anti-CD4 treatment. The level of OTC expression from the third viral infusion, however, was lower than that from the second viral infusion. Passive transfer experiments suggest that low levels of neutralizing antibodies developing over repeated viral administration was the likely cause of the reduced transgene expression. Together, these findings demonstrated that the host immune system can be modulated to permit effective transgene expression at therapeutic levels by re-administered adenoviral vectors.

Adenoviridae↗