Research

Liver abscess in a boy with hyper IgE syndrome.

J Family Med Prim Care. 2016 Apr-Jun;5(2):491-492

Authors: Nandy S, Shah I

Abstract
Hyper immunoglobulin-E syndrome is a rare primary immunodeficiency disease, characterized by the classical triad of recurrent staphylococcal skin abscesses, pneumonia with pneumatocele formation, and elevated levels of serum IgE, usually over 2000 IU/mL. Chronic granulomatous disease, hyper IgE, and complement deficiencies are immunopathologies known to be associated with liver abscesses. We present a 2 ½-year-old boy with liver abscess and associated hyper IgE.

PMID: 27843873 [PubMed – in process]

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Primary Immunodeficiency: New Insights and Practical Clinical Approaches.

J Allergy Clin Immunol Pract. 2016 Nov – Dec;4(6):1109-1110

Authors: Cunningham-Rundles C

PMID: 27836060 [PubMed – in process]

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The Nuts and Bolts of Immunoglobulin Treatment for Antibody Deficiency.

J Allergy Clin Immunol Pract. 2016 Nov – Dec;4(6):1076-1081.e3

Authors: Wasserman RL

Abstract
Immunoglobulin therapy is a key element in the management of most patients with primary immunodeficiency disease. Allergist/immunologists should be familiar with the appropriate evaluation of candidates for immunoglobulin, the characteristics of immunoglobulin products, and how to use them to provide the best care to their patients. Available immunoglobulin products appear to be equally efficacious, but they are not interchangeable. Minimizing the risk of serious adverse events and controlling minor side effects is important to ideal patient care. Immunoglobulin may be administered intravenously or subcutaneously. Individualizing the choice of immunoglobulin product, mode of administration, and site of care can optimize the clinical outcome and minimize the burden of care.

PMID: 27836057 [PubMed – in process]

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Primary Immune Deficiencies in the Adult: A Previously Underrecognized Common Condition.

J Allergy Clin Immunol Pract. 2016 Nov – Dec;4(6):1101-1107

Authors: Rosenberg E, Dent PB, Denburg JA

Abstract
The large majority of classified primary immune deficiency (PID) diseases present in childhood. Yet, most patients with PID are adults, with a large proportion experiencing onset of symptoms beyond their childhood years. Most of these are diagnosed predominantly with antibody defects, but cellular and other disorders are increasingly being identified in older patients as well. Moreover, advances in clinical immunology are allowing pediatric patients, even those with severe disease, to reach adulthood. Because of differences in the physiology and pathophysiology of children and adults, the presentation, diagnosis, and management of a complex chronic disease could differ significantly between these patient populations and therefore require modifications in approach.

PMID: 27836059 [PubMed – in process]

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Lung Disease in Primary Antibody Deficiencies.

J Allergy Clin Immunol Pract. 2016 Nov – Dec;4(6):1039-1052

Authors: Schussler E, Beasley MB, Maglione PJ

Abstract
Primary antibody deficiencies (PADs) are the most common form of primary immunodeficiency and predispose to severe and recurrent pulmonary infections, which can result in chronic lung disease including bronchiectasis. Chronic lung disease is among the most common complications of PAD and a significant source of morbidity and mortality for these patients. However, the development of lung disease in PAD may not be solely the result of recurrent bacterial infection or a consequence of bronchiectasis. Recent characterization of monogenic immune dysregulation disorders and more extensive study of common variable immunodeficiency have demonstrated that interstitial lung disease (ILD) in PAD can result from generalized immune dysregulation and frequently occurs in the absence of pneumonia history or bronchiectasis. This distinction between bronchiectasis and ILD has important consequences in the evaluation and management of lung disease in PAD. For example, treatment of ILD in PAD typically uses immunomodulatory approaches in addition to immunoglobulin replacement and antibiotic prophylaxis, which are the stalwarts of bronchiectasis management in these patients. Although all antibody-deficient patients are at risk of developing bronchiectasis, ILD occurs in some forms of PAD much more commonly than in others, suggesting that distinct but poorly understood immunological factors underlie the development of this complication. Importantly, ILD can have earlier onset and may worsen survival more than bronchiectasis. Further efforts to understand the pathogenesis of lung disease in PAD will provide vital information for the most effective methods of diagnosis, surveillance, and treatment of these patients.

PMID: 27836055 [PubMed – in process]

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Vaccination in Primary Immunodeficiency Disorders.

J Allergy Clin Immunol Pract. 2016 Nov – Dec;4(6):1066-1075

Authors: Sobh A, Bonilla FA

Abstract
Immunocompromised patients have increased susceptibility to vaccine-preventable infections. Thus, vaccination is a critical issue in this population. Vaccines are usually classified as live versus inactivated or subunit (nonviable) vaccines. In general, inactivated vaccines are safe in immunocompromised patients and should be given per the routine schedule except when they are unlikely to have any benefit as in severe antibody deficiency or combined immunodeficient patients and patients receiving immunosuppressive therapy or immunoglobulin replacement. However, viable vaccines usually carry the risk of causing disease, especially in severely immunocompromised patients. Therefore, much greater caution must be exercised with the use of viable vaccines and administration is individualized on the basis of the estimated risk of infections if not vaccinated versus the potential adverse effects of the vaccine itself. In this review, we make clear recommendations on the basis of available evidence regarding both routine and specialized vaccines, viable and nonviable, and the degree of immune compromise in all the categories of immunodeficiency disorders.

PMID: 27836056 [PubMed – in process]

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Clinical Phenotypes of Hyper-IgM Syndromes.

J Allergy Clin Immunol Pract. 2016 Nov – Dec;4(6):1023-1036

Authors: de la Morena MT

Abstract
The primary immunodeficiency (PID) diseases comprise a heterogeneous group of inherited disorders of immune function. Technical advancements in whole-genome, whole-exome, and RNA-sequencing have seen the explosion of genetic discoveries in the field of PIDs. The present review aims to focus on a group of immunodeficiency disorders associated with elevated levels of IgM (hyper IgM; HIGM) and provides a clinical differential diagnosis. Most patients present for evaluation of immunodeficiency due to recurrent infections, and laboratory studies show either a clear isolated elevation of serum immunoglobulin M (IgM) with low or absent IgG, IgA, and IgE. Alternatively, IgM levels may be normal or moderately elevated while other serum immunoglobulins are reported below the norms for age but not absent. Mechanistically, these disorders are recognized as defects in immunoglobulin (Ig) class switch recombination (CSR). Importantly, to safeguard genetic stability, CSR utilizes elements of the DNA repair machinery including multi-protein complexes involved in mismatch repair (MMR). Therefore, it is not uncommon for defects in the DNA repair machinery, to present with laboratory findings of HIGM. This review will discuss clinical phenotypes associated with congenital defects associated with HIGM. Clinical manifestations, relevant immunologic testing, inheritance pattern, molecular diagnosis, presumed pathogenesis, and OMIM number, when annotated are compiled. Accepted therapeutic options, when available, are reviewed for each condition discussed.

PMID: 27836054 [PubMed – in process]

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Transient hypogammaglobulinaemia of infants in children with mastocytosis – strengthened indications for vaccinations.

Cent Eur J Immunol. 2016;41(3):282-286

Authors: Renke J, Lange M, Dawicka J, Adamkiewicz-Drożyńska E

Abstract
Mastocytosis is a disease caused by the accumulation of mast cells (MC) in the skin and/or in other tissues. Both the cutaneous form of the disease (CM) predominating in children and the systemic form (SM) typical for adults are associated with the occurrence of MC mediator-related symptoms. The release of mediators can be induced by physical stimuli and/or specific triggering factors. The routine vaccination program performed in the majority of children in infancy can be considered as an additional factor provoking exacerbation of CM. Conscious of the important role of MC in the innate immunity, we have analysed retrospective data concerning the levels of immunoglobulins, an adaptive factor, in a group of 74 infants and toddlers with CM. The values corresponding to transient hypogammaglobulinaemia of infants (THI) were found in 8 (10.81%) of cases. Classification of the antibody deficiency was done according to the working definitions for clinical diagnosis of primary immunodeficiency of the European Society of Immunodeficiencies (ESID) Registry – version May 11, 2015. Following the retrospective data, the final diagnosis of THI cannot be made due to the young age of the study group. The percentage may significantly exceed the published incidence of THI, i.e. about 0.11%. The results of our study may indicate, importantly, a higher incidence of THI in childhood-onset mastocytosis than in the general paediatric population and strengthen indications for vaccinations. In conclusion, we suggest that THI may be considered as a new aspect of paediatric mastocytosis that requires further investigation.

PMID: 27833446 [PubMed – in process]

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A Case of IL-7R Deficiency Caused by a Novel Synonymous Mutation and Implications for Mutation Screening in SCID Diagnosis.

Front Immunol. 2016;7:443

Authors: Gallego-Bustos F, Gotea V, Ramos-Amador JT, Rodríguez-Pena R, Gil-Herrera J, Sastre A, Delmiro A, Rai G, Elnitski L, González-Granado LI, Allende LM

Abstract
Reported synonymous substitutions are generally non-pathogenic, and rare pathogenic synonymous variants may be disregarded unless there is a high index of suspicion. In a case of IL7 receptor deficiency severe combined immunodeficiency (SCID), the relevance of a non-reported synonymous variant was only suspected through the use of additional in silico computational tools, which focused on the impact of mutations on gene splicing. The pathogenic nature of the variant was confirmed using experimental validation of the effect on mRNA splicing and IL7 pathway function. This case reinforces the need to use additional experimental methods to establish the functional impact of specific mutations, in particular for cases such as SCID where prompt diagnosis can greatly impact on diagnosis, treatment, and survival.

PMID: 27833609 [PubMed – in process]

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Successful engraftment after hematopoietic stem cell transplantation with infusion of donor stem cells through the extracorporeal membrane oxygenation circuit.

Indian J Crit Care Med. 2016 Oct;20(10):617-619

Authors: Anton-Martin P, Darnell-Bowens C, Aquino VM, Jones T, Raman L

Abstract
Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene expressed in hematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice when an appropriate human leukocyte antigen-matched donor is available. The use of the extracorporeal membrane oxygenation (ECMO) circuit to infuse donor cells for HSCT has not been previously published in the literature. We describe a case of a child who had successful engraftment after HSCT with infusion of the donor stem cells through the ECMO circuit.

PMID: 27829721 [PubMed – in process]

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