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)

Twenty three patients with primary immunoglobulin(Ig) deficiency were seen during the last ten years. Nine had hypogamma globulinemia (hypo-Ig) and the rest, selective Ig deficiency. Most were in pediatric age group. There was preponderance of males with only one female. Clinical symptoms pertaining to gastrointestinal and sinupulmonary infections were most common. Complete absence of B cells was not observed in any patient with hypogammaglobulinemia. They could be typed as physiological in one patient, X-linked immunodeficiency in 2 patients and common variable immunodeficiency in the remaining six. Three patients with selective IgA deficiency were above 20 years of age. Two had only secretory IgA deficiency, confirmed by jejunal fluid examination and the rest had both secretory and serum IgA deficiency. Low IgM was seen in one patient. We see a spectrum of immunoglobulin deficiencies varying from subtle defects like absence of secretory IgA only, to severe depletion of all immunoglobulins. Therapy is still not ideal due to economic reasons.
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PMID:Immunoglobulin deficiency. 828 26

The most common form of primary immunodeficiency is IgA deficiency (IgAD). However, the molecular basis of this disease remains elusive. Therefore, to address this issue we made a systematic analysis of the molecular events leading to IgA production. B lymphocytes that produce IgA have undergone somatic rearrangement that joins the switch (S) mu to S alpha region with deletion of the intervening sequences. Examination of the resulting S mu/S alpha junctions in unstimulated PBMC from IgAD patients by nested primer PCR revealed a significant decrease in the number of the S mu/S alpha fragments. To obtain the antisense primers to generate the S mu/S alpha fragments, we sequenced the human S alpha 1 and the downstream region extending to the C alpha 1 locus. Similar to previously reported switch sequences, we also found the S alpha 1 to be predominantly composed of pentameric repeats GAGCT and GGGCT. The decrease in the number of S mu/S alpha fragments is consistent with a profound decrease in the C alpha membrane mRNA expression in unstimulated PBMC, as well as in the C alpha mRNA levels and IgA production in PWM-stimulated PBMC. Sequence analysis of the switch junctions from IgA-producing cell lines, control donors, and an IgAD patient showed direct joining in 8 of 9 cases examined. TGF-beta 1, previously shown to be the switch factor for human and mouse IgA, was also examined. No difference in the TGF-beta 1 mRNA levels in unstimulated PBMC between the control subjects and the IgAD patients were detected. Our findings indicate that the failure to switch to IgA-producing B lymphocytes, or an impaired survival of such cells, may be an important molecular mechanism in IgAD.
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PMID:Molecular analysis of IgA deficiency. Evidence for impaired switching to IgA. 830 Nov 44

Expression of the gamma/delta T cell receptor (TCR) on CD3+ intraepithelial lymphocytes (IELs) was studied by two-colour immunofluorescence in duodenal tissue sections from healthy (n = 6) or infection-prone (n = 7) subjects with selective IgA deficiency (IgAD), and subjects (n = 4) with combined IgAD and IgG subclass deficiency. TCR gamma/delta+ IEL proportions in selective IgAD subjects (median 6.3%, range 1.0-41%) and in those with combined deficiency (median 4.5%, range 1.2-33%) were well within the range (0.3-38%) for histologically normal controls (n = 11), but the healthy IgAD subgroup tended to show raised TCR gamma/delta+ IEL proportions (median 13.6%) compared with the other two subgroups. Also the number of TCR gamma/delta+ IELs per intestinal length unit was relatively high (median 13.9/mm) in the healthy IgAD subjects, and significantly raised (P < 0.03) compared with controls (median 3.2/mm). Paired staining revealed that most TCR gamma/delta+ IELs in both selective IgAD (98%) and combined deficiency (99%) were CD8-, and a large fraction (median 84% and 63%, respectively) expressed the V delta 1/J delta 1-encoded epitope. The total number of CD3+ IELs (mostly CD8+) was similar to controls. IgAD subjects, and especially the healthy subgroup, had significantly increased serum concentrations of soluble CD8 (P < 0.0002), neopterin (P < 0.005), and beta 2-microglobulin (P < 0.007), which was similar to our previous observations in common variable immunodeficiency, and probably reflected stimulation of cell-mediated immunity. In addition, the increased TCR gamma/delta+ IELs might reflect a component of compensatory surface protection in the healthy IgAD subgroup.
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PMID:Duodenal intraepithelial gamma/delta T cells and soluble CD8, neopterin, and beta 2-microglobulin in serum of IgA-deficient subjects with or without IgG subclass deficiency. 840 24

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency with recurrent infections, IgA and IgE deficiency, and increased incidence of malignancies. The pathognomonic biological abnormalities consist of spontaneous chromosomal instability resulting in a high in vivo occurrence of cells with translocations, especially involving chromosomes 7 and 14, and a relative insensitivity of DNA replication in vitro to radiation exposure. We report on a patient with the biological hallmarks of AT but with atypical clinical manifestations. Although progressive cerebellar ataxia was present, the neurological picture was broader than that usually seen in AT and included peripheral polyneuropathy and spinal atrophy. On the other hand, telangiectasias, recurrent infections, malignancies, IgA deficiency, or other immunological abnormalities were not present. This illustrates that the clinical picture of AT is broad and nonspecific, and highlights the diagnostic value of cytogenetic analysis and studies of radioresistance of DNA synthesis.
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PMID:Atypical clinical presentation of ataxia telangiectasia. 845 62

A statistically significant increase of selective IgA deficiency was found evaluating 52 first degree relatives of 15 patients with common variable immunodeficiency, 4/5 of these cases were observed in the children of our patients. In addition to this decreased mean serum IgM level and increase of frequency of antithyroid autoantibodies compared to control subjects were observed. An excess of rheumatoid factor or antinuclear antibodies as not observed.
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PMID:[Immunologic laboratory findings in relatives of patients with common variable immunodeficiency]. 847 88

IgA deficiency is the most common humoral defect in man and results in an increased susceptibility to respiratory tract and gastrointestinal infections. Both clinical and genetic data support a close relationship with common variable immunodeficiency, a disease which involves not only IgA and IgG production, but also, in half of the patients, IgM. It is likely that the two disorders represent an allelic condition with a variable expression of a common gene defect which is thought to be involved in the regulation of immunoglobulin class switching. It is possible that a single, autosomally inherited gene with a limited penetrance is responsible for the development of both these defects.
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PMID:Genetics of IgA deficiency. 856 23

IgA deficiency (IgA-D) represents the most common immunodeficiency syndrome of infancy. In most cases IgA-D represents an isolated immunological disorder, while sometimes it is associated with IgG subclass deficiency or with the presence of autoantibodies. We investigated the pattern of association of IgA-D with DRB1 and DQB1 loci of the HLA region by DNA molecular typing, which allows the identification of previously serologically undefined specificities. We also compared the gene frequency of DRB1 and DQB1 allelic variants between IgA-D subjects with or without serum autoantibodies. Our results indicate that the gene frequency of the DRB1*0102 subtype and of the DRB1*0102, DQB1*0501 haplotype is significantly higher in IgA-D than in the general population. Furthermore, the IgA-D subjects with autoantibodies showed a positive association with DR4 and DR13 subtypes, thus supporting the hypothesis that genetic factors are also involved in the association between IgA-D and autoantibodies.
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PMID:DNA typing of DQ and DR alleles in IgA-deficient subjects. 858 46

A 7-year and 11 month-old girl with cerebellar astrocytoma linked to familial ataxia-telangiectasia (AT) is presented. She was born as the 7th girl of a woman with aortic arch syndrome. Two elder sisters of the patient have ataxia telangiectasia. She had immunodeficiency, and cerebellar ataxia, but had no oculocutaneous telangiectasia. The risk of cancer developing in AT patients is about 1,200 times greater than that in age-matched controls. With regard to central nervous system tumours, seven primary tumours have been reported, such as 3 cases of medulloblastoma and 4 cases of glioma. Members of AT families who were under the age of 45 had a risk of dying of a malignant neoplasm five times greater than in the general population. However, there were no reports of glioma in AT families. In this case, it is suggested that IgA deficiency linked to familial AT may have contributed to the development of astrocytoma.
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PMID:Astrocytoma linked to familial ataxia-telangiectasia. 874 98

IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) are two primary immunodeficiencies that share clinical features. Occasionally, both diseases have been diagnosed in the same family, which suggests the existence of some common pathogenic mechanism, but progression from IgA-D to CVID has rarely been documented. We report three cases of CVID diagnosed 1 to 12 years after IgA-D was detected. Two of these patients presented autoimmune diseases followed by a progressive decline in IgG levels. They are currently on intravenous immunoglobulin therapy with complete remission of their autoimmune and infectious symptoms.
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PMID:Development of a common variable immunodeficiency in IgA-deficient patients. 917 22

The screening of humoral immunity was performed in 6280 children with recurrent infections. The low level of immunoglobulins was detected in 287 children. The most frequently were: the decreased level of IgA (142 children), and selective IgA deficiency (78 children). The decreased level of all classes of immunoglobulins was rare. Within this group of children severe immunodeficiency diseases (Omenn syndrome, Seemanov syndrome, SCID with NK predominance or MHC class II deficiency) were diagnosed.
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PMID:[Incidence of humoral immunodeficiency in children with recurrent infections]. 883 39


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