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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The package inserts of live viral vaccines include immunodeficiency as a contraindication. Nevertheless, patients with mild forms of immunodeficiency may benefit from vaccination. No published guidelines exist for the administration of these vaccines specifically to patients with chromosome 22q11.2 deletion syndrome. This syndrome is also sometimes called DiGeorge syndrome and is associated with thymic hypoplasia and diminished T-cell numbers and has a wide spectrum of phenotypic features that include cardiac anomalies, dysmorphic facial features, and hypocalcemia. Patients generally exhibit a mild to moderate decrement in T-cell numbers with preservation of T-cell function. The aims of this study were to investigate the incidence of side effects after live viral vaccine administration in a population with chromosome 22q11.2 deletion syndrome. The high frequency of this syndrome in the population (1:3000 children) mandates a greater understanding of the risks and benefits related to live viral vaccine administration. A retrospective analysis of vaccine adverse events was performed. The data acquisition form evaluated the frequency of live vaccine administration and the consequences of both vaccination and withholding the vaccine. Flow cytometric enumeration of T cells was performed as part of an immunologic evaluation. Thirty-two of 59 responders were vaccinated with the varicella vaccine. Only 9% of patients reported adverse events. However, 63% of unvaccinated children developed chickenpox. Comparison of patients who tolerated the vaccine with those who reported adverse events showed no statistically significant differences in current age (7 vs 5.7 years), age at vaccination (3 vs 2.5 years), or T-cell subset counts: CD3 (1951 vs 2083 cells/ microL), CD4 (1283 vs 1463 cells/ microL), and CD8 (530 vs 502 cells/ microL). Fifty-two of 59 responders were vaccinated with measles-mumps-rubella (MMR). Twelve (23%) of 52 reported mild side effects, including fever, rash, and constitutional symptoms. No severe adverse reactions were reported. No patient reported natural disease with measles, mumps, or rubella. There were no statistically significant differences between the T-cell counts in the vaccinated group reporting side effects versus the vaccinated group without side effects (mean CD3 counts: 1928 vs 1736 cells/ microL; CD4 counts: 1250 vs 1127 cells/ microL; and CD8 counts: 528 vs 483 cells/ microL). In our study, patients with chromosome 22q11.2 deletion syndrome had a similar incidence of adverse effects with varicella and MMR vaccines compared with that reported in the general population. All side effects were mild. However, in patients who did not receive the varicella vaccine, an overwhelming 63% contracted the disease. Patients who were not vaccinated against MMR did not develop natural disease. The data suggest that this is a cohort of patients with 22q11.2 deletion syndrome who have tolerated live viral vaccinations without evidence of significant side effects. A prospective study could address whether there are T-cell thresholds below which vaccination is unsafe; however, the information that we present suggests that vaccinating children with chromosome 22q11.2 deletion with live viral vaccines does not carry a significantly higher risk of adverse reactions compared with the general population, provided that they have no evidence of severe immunocompromise.
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PMID:Safety of live viral vaccines in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). 1452 20

Patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) typically exhibit thymic hypoplasia, conotruncal cardiac defects, and hypoparathyroidism. The immunodeficiency that results from the thymic hypoplasia has been extensively described and consists primarily of T-cell lymphopenia. A curious feature of the T-cell lymphopenia is that the age-related rate of decline of T-cell numbers is slower in patients than controls. This leads to T-cell numbers in adulthood that are minimally decreased compared with controls. This suggests that homeostatic mechanisms might be acting to preserve the peripheral blood T-cell numbers in patients. We characterized changes in CD4/CD45RA and CD4/CD45RO T-cell populations in patients and controls of various ages and determined T-cell recombination excision circles and telomere length within the CD4/CD45RA population. Patients had evidence of accelerated conversion of naive to memory cells and had evidence of more extensive replicative history within the CD4/CD45RA compartment compared with controls. Oligoclonal T-cell receptor (TCR) Vbeta families and missing Vbeta families were seen more often in patients than controls. These data are consistent with homeostatic proliferation of T cells in patients with limited T-cell production due to thymic hypoplasia.
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PMID:T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. 1452 74

Partial DiGeorge syndrome (pDGS) is an inherited primary immunodeficiency syndrome (incidence, 1:3000 live births) primarily affecting cellular immune function; partial, infers thymic hypoplasia with detectable circulating T-lymphocytes and adequate function. No guidelines exist regarding the recommendations for use of live viral vaccines (LVVs) in this extensive population of pediatric patients. We reviewed the experience with live viral vaccines in our cohort of patients with pDGS. Of 53 patients, 25 (47%) had received a live viral vaccine. No significant adverse events were recorded in association with administration of live viral vaccines. There was no statistically significant difference between cellular immune function at initial presentation between those patients that received live viral vaccines and those that did not. Adequate cellular immune function was documented for 15 of the 25 LVV recipients at the time of vaccine administration without significant change from baseline. These observations suggest that live viral vaccines appear safe in patients with pDGS and stable immune function.
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PMID:Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity. 1520 87

Fetal tissue is the richest source of primordial stem cells and has several properties that make it particularly useful for transplantation. It is superior to adult (mature) tissue in certain respects. First, fetal cells are capable of proliferating faster and more often than mature, fully differentiated cells. This means that these donor cells are able to quickly reverse the lost function of the host. In addition, these fetal cells can often differentiate in response to the environmental cues around them. This is because of their location--they can grow, elongate, migrate, and establish functional connections with other cells around them in the host. It has been found that fetal tissue is not easily rejected by the recipient due to the low levels of histocompatibility antigens in the fetal tissue. At the same time, angiogenic and trophic factors are at high levels, enhancing their ability to grow once they are transplanted. Since early fetal hematopoietic tissue lacks lymphocytes, graft vs host reactions are minimized. Fetal cells tend to survive excision, dissection, and grafting better because they generally do not have long extensions or strong intercellular connections. Finally, fetal tissue can survive at lower oxygen levels than mature cells. This would make them more resistant to the ischemic conditions found during transplantation or in vitro situations. Studies on fetal cell/tissue transplant have been encouraging. Fetal tissue can be used in different indications, for instance, fetal liver transplants may be used in combating aplastic anemia, placental umbilical cord whole blood transfusion can serve as an emergency alternative to adult whole blood transfusion, fetal adrenal transplant has been tried in combating intractable pain in arthritis, and fetal thymic transplant in combating leucopenia in non-Hodgkin's lymhoma and other immunodeficiency conditions like DiGeorge Syndrome, only to name a few. Fetal brain tissue transplant has also been done in a heterotopic site and the proliferation of the tissue has been observed. Neurotransplantation with fetal tissue in Parkinsonism shows positive results in some globally accepted studies. There are futuristic potential uses of fetal tissue in bioengineering through coating/seedling of fetal tissue on implants, stents and other artificial surgical life-saving devices to improve their functioning, and it may also extend the life of these costly gadgets. By properly using pre-HLA fetal tissue seedling in orthopedic, thoracic and also neurosurgical appliances, there could be a reduction of long-term irritation sequelae of the implant and the host interphase, and thus, a better device, i.e., a more biofriendly interphase could be developed. This may help in the reduction of pseudomembrane formation, loss of patency and other resultant TH2 reactions of the host system.
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PMID:Fetal cell/tissue therapy in adult disease: a new horizon in regenerative medicine. 1549 Oct 58

The vast majority of known primary immunodeficiencies (PIDs) are autosomal or X-linked recessive Mendelian traits. Only four classical primary immunodeficiencies are thought to be autosomal-dominant, three of which still lack a well-defined genetic etiology: isolated congenital asplenia, isolated chronic mucocutaneous candidiasis, and hyper IgE syndrome. The large deletions on chromosome 22q11.2 associated with Di George syndrome suggest that this disease may be dominant but not Mendelian, possibly involving several genes. The clinical and genetic features of six novel autosomal-dominant primary immunodeficiencies have however been described in recent years. These primary immunodeficiencies are caused by germline mutations in seven genes: ELA2, encoding a neutrophil elastase, and GFI1, encoding a regulator of ELA2 (mutations associated with severe congenital neutropenia); CXCR4, encoding a chemokine receptor (warts, hypogammaglobulinemia, infections and myelokathexis syndrome); LCRR8, encoding a key protein for B-cell development (agammaglobulinemia); IFNGR1, encoding the ligand-binding chain of the interferon-gamma receptor; STAT1, encoding the signal transducer and activator of transcription 1 downstream from interferon-gammaR1 (Mendelian susceptibility to mycobacterial diseases); and IKBA, encoding IkappaBalpha, the inhibitor alpha of NF-kappaB (anhidrotic ectodermal dysplasia with immunodeficiency). These recent data suggest that many more autosomal-dominant PIDs are likely to be identified in the near future.
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PMID:Autosomal-dominant primary immunodeficiencies. 1560 87

Live attenuated vaccines are usually contraindicated in patients with congenital or acquired immunodeficiency. On the other hand, infections due to wild type virus may be particularly severe in patients with low levels of T cells. The aim of the present study was to evaluate safety and immunogenicity of measles-mumps-rubella (MMR) vaccine in children with congenital T cell defect (DiGeorge anomaly). Fourteen patients were included in the study. No severe adverse reaction was reported. No difference between patients and controls was found in frequency of seroconversion for both measles (92.9% versus 96.3%) and rubella (92.9% versus 100%). No difference in mean titres of anti-measles (1.62+/-0.54 versus 1.89+/-0.49 index) (p=0.13) or anti-rubella (78.1+/-48.0 versus 72.0+/-41.0 UI/ml, p=0.68) antibodies was found between patients and controls. No decrease in CD4 cells was detected after immunization. MMR vaccine is immunogenic and can be safely used in patients with DiGeorge anomaly, so preventing severe complication due to wild virus infection.
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PMID:Safety and immunogenicity of measles-mumps-rubella vaccine in children with congenital immunodeficiency (DiGeorge syndrome). 1570 70

Data collection for the national registry for patients with primary immunodeficiency disorders in the Republic of Ireland commenced in 1996. One hundred and fifteen cases of primary immunodeficiency diseases were registered between December 1996 and February 2003. The most frequent primary immunodeficiency disorders were antibody deficiency (n = 53) and complement deficiency (n = 32). In addition, patients with T cell deficiency (n = 11) and chronic granulomatous disease (n = 11) were identified. A small number of patients with Wiskott-Aldrich syndrome, natural killer cell deficiency, DiGeorge syndrome and chronic mucocutaneous candidiasis were also registered. Comparison of our data with that recently reported in the European registry revealed that complement deficiency was more prevalent in the Republic of Ireland compared to other European countries. Results of our registry point to a significant prevalence of primary immunodeficiency disorders in the Republic of Ireland (2.9 cases per 100,000 population). However, it is likely that these figures underestimate the true prevalence of such cases in the country. We hope, with increased awareness of the national registry among primary care physicians, that more patients will be included and we will be able to identify accurately the frequency and the distribution of these disorders.
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PMID:Primary immunodeficiency disorders in the Republic of Ireland: first report of the national registry in children and adults. 1574 60

DiGeorge syndrome (DGS) is a congenital disorder characterized by typical facial features, hypoparatyroidism, conotruncal cardiac defects and thymic hypoplasia. Although there are some reports addressing lymphocytes counts and function in DGS children over time, few data have been reported on the T-cell receptor V beta (TCRBV) repertoire in relation to disease progression. The aim of this study was to evaluate the degree and nature of immunodeficiency and to investigate a possible correlation to clinical findings. We used third complementary region (CDR3) size spectratyping as a tool for monitoring T-cell repertoire diversity in 7 DGS's children. The rate of thymic output, the phenotype and function of peripheral T-cells and the humoral immunity were also investigated. At baseline a profound alteration of the TCR repertoire was noted, mainly in the CD8+ T-cells, in DGS patients when compared to a control group. Furthermore, analysis of thymic output showed a significant decrease in TCR rearrangement excision circles (TRECs) levels in the patient group. Immunoglobulin abnormalities were also detected. The observed TCR repertoire alterations, although not statistically significant, may suggest an increased susceptibility to infections. A parallel increase in the TCR repertoire diversity and clinical improvement occurred during the follow-up. Our results confirm that the extent of immunodeficiency is highly variable and could improve through childhood, and indicate that TCR repertoire may be a useful marker to clinically monitor thymic function in this primary immunodeficiency.
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PMID:Post-natal ontogenesis of the T-cell receptor CD4 and CD8 Vbeta repertoire and immune function in children with DiGeorge syndrome. 1598 Oct 92

We report an atypical case of complete DiGeorge (DG) anomaly that presented initially exclusively as severe combined immunodeficiency (SCID). The child had severe infections at diagnosis, in keeping with the SCID phenotype; however, normal lymphocyte counts and immunoglobulin levels were noted at admission, which delayed diagnosis. Importantly, the child presented without neonatal hypocalcemia or velofacial or cardiac abnormalities at the time of diagnosis, which masked underlying DG. This case outlines the difficulties in making the diagnosis of SCID in a timely manner and illustrates the variation in presentation of the 22q11.2 deletion syndrome. There should be a high index of suspicion for primary immunodeficiency among children with severe infections and, because management may vary, DG anomaly should be considered in the differential diagnosis of T- B+ natural killer+ SCID.
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PMID:Complete DiGeorge anomaly in the absence of neonatal hypocalcemia and velofacial and cardiac defects. 1606 70

The authors selected articles published in the literature from January 2004 through December 2004 that were relevant to the areas of basic and clinical immunology. Several articles explored the development of TH1 or TH2 response and the role of the monocyte-T cell interaction. Others were articles describing the action of drugs commonly used in asthma to inhibit cytokine responses and the anti-inflammatory role of nonimmune pulmonary cells present in the lung. Several reports show how dendritic cells are being developed as vehicles for DNA vaccines aimed at stimulating cellular responses, an advance of great importance for HIV researchers working on vaccines, who are concerned about the different ways HIV evades the immune response. Other publications described Toll-like receptors in diverse cells, including mast cells and CD4+ T cells, for the recognition of viruses and bacteria. In the area of clinical immunology, an updated classification for primary immunodeficiencies with more than 100 identified genes responsible for these diseases and the report on the second clinical trial of gene therapy for X-linked severe combined immunodeficiency syndrome were published. Significant advances included the clinical prognosis in common variable immunodeficiency for patients presenting with lung pathology, the safety of live vaccines in partial DiGeorge syndrome, the report of patients with complete DiGeorge syndrome with the presence of peripheral blood T cells, the clinical spectrum of patients with NF-kappaB essential modifier (NEMO) gene deficiency, the publication of a consensus algorithm for the management of hereditary angioedema, and the report of immune restoration syndrome in pediatric HIV infection.
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PMID:Basic and clinical immunology. 1608 98


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