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Primary Immunodeficiency (primary + immunodeficiency)

Distribution by Scientific Domains

Medical Sciences	93%

Terms modified by Primary Immunodeficiency

primary immunodeficiency disease

Selected Abstracts

Novel primary immunodeficiencies relevant to internal medicine: novel phenotypes

JOURNAL OF INTERNAL MEDICINE, Issue 6 2009
L. Maródi
Abstract. Primary immunodeficiencies (PIDs) are often recognized in adults, either because of delayed diagnosis of a paediatric illness, or increasingly because of the recognition of adult onset forms of these diseases. Moreover, a growing fraction of children diagnosed with PIDs reach adulthood. It has become clear that many of these conditions affect various organs and therefore will be referred to professionals from various fields of internal medicine. It is well known that infectious diseases, allergy, auto-immunity and cancer may result from PIDs. Surprisingly, other clinical manifestations were recently found to reflect inborn errors of immunity. Ground-breaking discoveries suggest that atypical haemolytic uraemic syndrome, Crohn's disease, and alveolar proteinosis may actually be manifestations of novel PIDs. [source]

Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency

HUMAN MUTATION, Issue 4 2001
Luigi D. Notarangelo
Abstract During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3 -gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T,B+ SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families. Hum Mutat 18:255,263, 2001. © 2001 Wiley-Liss, Inc. [source]

Inherited disorders of human Toll-like receptor signaling: immunological implications

IMMUNOLOGICAL REVIEWS, Issue 1 2005
Cheng-Lung Ku
Summary:,In vitro nine of 10 known human Toll-like receptors (TLRs) are engaged by well-defined chemical agonists that mimic microbial compounds, raising the possibility that human TLRs play a critical role in protective immunity in vivo. We thus review here the recently described human primary immunodeficiencies caused by germline mutations in genes encoding molecules involved in cell signaling downstream from TLRs. Subjects with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) carry either X-linked recessive hypomorphic mutations in NEMO or autosomal dominant hypermorphic mutations in IKBA. Their cells show a broad defect in nuclear factor-,B (NF-,B) activation, with an impaired, but not abolished response to a large variety of stimuli including TLR agonists. EDA-ID patients show developmental anomalies of skin appendages and a broad spectrum of infectious diseases. Patients with autosomal recessive amorphic mutations in IRAK4 present a purely immunological syndrome and more restricted defects, with specific impairment of the Toll and interleukin-1 receptor (TIR),interleukin-1 receptor-associated kinase (IRAK) signaling pathway. In these subjects, the NF-,B- and mitogen-activated protein kinase-mediated induction of inflammatory cytokines in response to TIR agonists is impaired. The patients present a narrow range of pyogenic bacterial infections that become increasingly rare with age. Altogether, these data suggest that human TLRs play a critical role in host defense. However, they do not provide compelling evidence, as even the infectious phenotype of patients with mutations in IRAK4 may result from impaired signaling via receptors other than TLRs. Paradoxically, these experiments of nature raise the possibility that the entire set of human TLRs is largely redundant in protective immunity in vivo. [source]

Common variable immunodeficiency: 20-yr experience at a single centre

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2009
Ma Pilar Llobet
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It can present at any age in patients with a history of recurrent bacterial infections, with or without a family history of other primary immunodeficiencies (PID), and shows a wide range of clinical manifestations and immunological data. Diagnosis is based on low IgG, IgM and/or IgA levels. Delayed diagnosis and therapy can lead to bronchiectasis and malabsorption. The aim of this study was to describe a paediatric population diagnosed of CVID and its evolution in the population. Memory B-cell (MB) classification carried out in these patients was correlated with clinical manifestations and outcome. Clinical and immunological data of 22 CVID children under 18 yr treated at our centre between 1985 and 2005 are presented. Immunological studies included those for diagnosis and MB quantification. Differences in form of presentation, familial incidence and MB classification were reviewed. A statistical descriptive analysis was made. Infections were the commonest manifestation, affecting mainly respiratory (19/22) and gastrointestinal (10/22) tracts. Bronchiectasis was present in seven cases, and detected prior to CVID diagnosis in five. Replacement therapy led to a significant reduction in the number of infections. Severe complications appeared mostly in patients without MB. Patients of the same family share the same MB group. Family members had also been diagnosed of CVID in seven cases. Early diagnosis and therapy are essential to improve outcome in these patients. MB studies are useful in children to orient prognosis and further genetic studies. [source]

Rituximab for the treatment of post-bone marrow transplantation refractory hemolytic anemia in a child with Omenn's syndrome

PEDIATRIC TRANSPLANTATION, Issue 5 2007
Briuglia Silvana
Abstract:, Omenn's syndrome is a rare severe combined immunodeficiency that kills affected subjects before the end of the first year of life unless patients are treated with bone marrow transplantation (BMT). Unfortunately, post-BMT patients may develop autoimmune diseases, such as autoimmune hemolytic anemia (AIHA), which sometimes fails to respond to standard therapies. Rituximab is a chimeric, human, immunoglobulin G1/k monoclonal antibody specific for the CD20 antigen expressed on the surface of B lymphocytes. Rituximab is currently only labeled for treatment of B-cell lymphoproliferative disorders, such as B-cell non-Hodgkin's lymphoma and follicular lymphoma; however, it is also employed in the treatment of a variety of disorders mediated by auto-antibodies, such as AIHA and transplant-related autoimmune disorders. Herein, we describe the case of a 23-month-old male child with Omenn's syndrome, who had undergone BMT and was successfully treated with rituximab (375 mg/m2 intravenously, weekly for three times) for refractory post-BMT hemolytic anemia. Our findings evidence that rituximab should be considered for treatment of post-BMT AIHA refractory to traditional therapy also in children with primary immunodeficiencies; furthermore, rituximab might represent a means to obtain remissions without the toxic effects associated with corticosteroid and immunosuppressive agents. [source]

Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis in Wiskott-Aldrich syndrome

ACTA PAEDIATRICA, Issue 7 2003
S Pasic
A patient with Wiskott-Aldrich syndrome who developed Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is described in this study. At 4 mo of age the patient developed fever associated with bicytopenia and splenomegaly. Analysis of a bone marrow specimen revealed extensive haemophagocytosis, and in situ hybridization for EBV of the bone marrow specimen using an EBV-encoded RNA probe was positive. Diagnosis of EBV-HLH was established and immunotherapy with HLH-94 protocol was started. HLH has been described in patients with other well-defined primary immunodeficiencies such as X-linked lymphoproliferative syndrome, Chediak-Higashi syndrome and Griscelli disease. Also, HLH was reported recently in severe combined immunodeficiency and DiGeorge syndrome. Conclusion: The possibility of an underlying primary immunodeficiency should be considered in paediatric patients who present with HLH during infancy. [source]

Immunoglobulin A deficiency and oral health status: a case,control study

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2010
Gudmundur H. Jorgensen
Abstract Introduction: Immunoglobulin A (IgA) is important for mucosal health. Selective IgA deficiency (IgAD) is the most common primary immunodeficiency but its effect on oral health is unclear. The aim of this study was to investigate dental, periodontal and oral mucosal health in IgAD individuals. Material and methods: In total, 32 adult IgAD subjects were compared with 63 randomly selected individuals. Participants answered questionnaires regarding general and oral health and underwent oral examination, including examination using the periodontal screening and recording (PSR) system and dental examination using the DMF system. Results: The IgAD individuals had significantly more often undergone tonsillectomy (44%versus 24%, p=0.046) and adenoidectomy (31%versus 8%, p=0.003) compared with the controls. Furthermore, the IgAD subjects reported having pharyngitis, stomatitis and herpes labialis significantly more often. There was no significant difference in periodontal health (mean PSR index; 1.87 versus 1.77) or dental health (mean DMFS; 51.3 versus 53.7) between the two cohorts. A positive correlation between Helicobacter pylori infection and severity of periodontitis was found (p=0.036). Conclusion: IgAD predisposes to oral mucosal infections but does not influence periodontal or dental health. This is the first controlled study to include detailed clinical history and investigations, together with full oral and dental examination, in adults with IgAD. [source]

Women With Primary Antibody Deficiencies Requiring IgG Replacement Therapy: Their Perception of Prenatal Care During Pregnancy

JOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 5 2004
Susanne Hansen RN
Objective: To investigate how a group of women with primary antibody deficiencies (PAD) and receiving replacement therapy with IgG experienced the care they received in their prenatal clinics in relation to PAD and IgG therapy. Design: An exploratory study using a written questionnaire. Setting: The study originates from an immunodeficiency unit but evaluates care experienced at prenatal clinics. Participants: Nine women (25,43 years) attending an immunodeficiency unit and who fulfilled inclusion criteria for simultaneously having PAD, replacement IgG therapy, and full-term pregnancy (the latter within the past 5 years). Main outcome: Women's perception of the response of midwives and physicians at their prenatal clinics to their PAD and IgG therapy during pregnancy. Results: Women perceived that the obstetricians and the midwives had insufficient knowledge about PAD and IgG replacement therapy. Two women reported that their IgG therapy during pregnancy had been questioned. All nine women felt marginalized and unheard by staff regarding their PAD and need for IgG therapy. However, the women were satisfied with the checkups regarding the pregnancy as such. Conclusions: This study is the first attempt to investigate the prenatal experience of women with PAD (Search of PubMed, 1980 to present, including search terms primary immunodeficiency, pregnancy, and prenatal care). This study demonstrates that increased knowledge about PAD and IgG replacement therapy among midwives and physicians working in prenatal care clinics is needed. This can prevent misleading advice that puts the health of the mother and her fetus at risk. Sensitizing staff about this special group of women can create conditions in which women feel respected, heard, and satisfied with their prenatal care. [source]

Novel intraoral phenotypes in hyperimmunoglobulin-E syndrome

ORAL DISEASES, Issue 1 2008
DL Domingo
Aim:, Hyperimmunoglobulin-E syndrome (HIES) is a primary immunodeficiency characterized by eczema, recurrent skin and lung infections with pneumatocoele formation, and extremely elevated serum immunoglobulin-E. The precise immunologic defect and genetic etiology remain unknown. Non-immunologic findings include characteristic facial features (prominent forehead, fleshy nasal tip, and increased interalar distance); skeletal involvement (pathological fractures, scoliosis, and craniosynostosis); and retention of primary teeth. This study aims to characterize intraoral soft tissue findings in HIES patients. Methods:, Sixty HIES patients (4,54 years, 27 males, 33 females) received intraoral and radiographic evaluations. Chronological dental development was also assessed. Results:, Lesions of the hard palate and dorsal tongue were found in 55% and 60% of patients, respectively. Palatal lesions ranged from a generalized surface keratosis to a midline sagittal fibrotic bridge. Tongue lesions consisted of multiple fissures and a midline cleft. On the lip and buccal mucosa, keratotic plaques and/or surface fissures were found in 8% and 23% of patients, respectively. Manifested in 76.7% of patients, the intraoral lesions were significantly more prevalent than the characteristic facial traits (P = 0.0013). Conclusions:, Alterations in oral mucosa and gingiva were present in the majority of HIES patients. These novel intraoral findings may facilitate the diagnosis of HIES. [source]

Common variable immunodeficiency: 20-yr experience at a single centre

Serious Bacterial Infections in Febrile Outpatient Pediatric Heart Transplant Recipients

ACADEMIC EMERGENCY MEDICINE, Issue 10 2009
Shan Yin MD
Abstract Objectives:, The purpose of this study was to describe the incidence of serious bacterial infections (SBIs) in febrile outpatient pediatric heart transplant recipients and to assess the utility of using white blood cell (WBC) indices to identify patients at low risk for bacteremia. Methods:, A retrospective study was conducted on all heart transplant recipients followed at a single children's hospital. All outpatient visits from January 1, 1995, to June 1, 2007, in which fever was evaluated were reviewed. Patients with history of a primary immunodeficiency, receiving concurrent chemotherapy, or having had a stem cell or small bowel transplant were excluded. Demographic, historical, physical examination, laboratory, and radiographic data were then recorded. Results:, Sixty-nine patients had 238 individual episodes of fever evaluation; of these, 217 (91.2%) had blood cultures drawn with results available in their initial evaluation. There were six (2.8%) true-positive blood cultures and eight (3.7%) false-positive cultures. Chest radiography was done in 185 evaluations (77.8%), and 44 episodes of pneumonia (23.8%) were diagnosed. Of 112 urine cultures done, one (0.9%) was positive. Neither of two lumbar punctures performed were positive. In non,ill-appearing children without indwelling central lines or focal bacterial infections (pneumonia, cellulitis), the incidence of bacteremia was 1.2%. In children with a focal bacterial infection, the rate of bacteremia was 6.3%. WBC indices were not significantly different between bacteremic and nonbacteremic patients. A band-to-neutrophil ratio (BNR) of ,0.25 and a published guideline for identifying low-risk infants using WBC indices identified all bacteremic patients, each with a sensitivity of 100% (95% confidence interval [CI] = 48% to 100% and 54% to 100%, respectively). Conclusions:, The incidence of bacteremia was low in febrile, outpatient pediatric heart transplant patients, especially in those who were not ill-appearing and did not have a focus of serious infection. Two different low-risk criteria performed well in identifying the bacteremic patients, although given the low number of true-positive cultures, the CIs for the sensitivities of these tests were extremely wide, and neither test could be reliably used at present. A prospective multicenter study is required to confirm the low incidence of bacteremia and low-risk criteria in this population. [source]

Clinical Immunology Review Series: An approach to the patient with recurrent infections in childhood

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008
M. A. Slatter
Summary Recurrent or persistent infection is the major manifestation of primary immunodeficiency, which also results in atypical infection with opportunistic organisms. Young children are also vulnerable to infection and recurrent infection is common. While most children with recurrent infection have a normal immunity, it is important to recognize the child with an underlying primary immunodeficiency and investigate and treat appropriately and yet not over investigate normal children. Prompt, accurate diagnosis directs the most appropriate treatment, and early and judicious use of prophylactic antibiotics and replacement immunoglobulin can prevent significant end organ damage and improve long-term outlook and quality of life. This paper describes important presenting features of primary immunodeficiency and indicates when further investigation is warranted. [source]

Translational Mini-Review Series on Immunodeficiency: Molecular defects in common variable immunodeficiency

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007
C. Bacchelli
Summary Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10,15% of all cases of CVID and it is highly likely that further genetic defects will be identified. [source]

Investigation for immunodeficiency in patients with recurrent ENT infections

CLINICAL OTOLARYNGOLOGY, Issue 3 2001
T.R. Cooney
Patients suffering with primary immunodeficiency frequently present to ear, nose, and throat (ENT) clinics, but the diagnosis is rarely made at this time. Early diagnosis of these patients would help to prevent morbidity and even mortality. Normal results from a simple panel of blood tests will exclude the commonest immune deficiencies. An abnormal result from these tests, or a strong suspicion despite normal initial testing, should prompt discussion with an immunologist. [source]