Research

Chronic Diarrhea in Common Variable Immunodeficiency: a Case Series and Review of the Literature.

J Clin Immunol. 2017 Nov 14;:

Authors: Pecoraro A, Nappi L, Crescenzi L, D’Armiento FP, Genovese A, Spadaro G

Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition. We describe three female CVID adult patients presenting with chronic diarrhea, weight loss, and protein-energy malnutrition due to different underlying conditions. Our review of the literature explores the various gastrointestinal involvements in CVID and points out several histopathological findings proper of the disease, thus highlighting the relevance of the endoscopic and histological assessment in CVID patients presenting with chronic diarrhea.

PMID: 29138951 [PubMed – as supplied by publisher]

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Long-term observational studies of chronic granulomatous disease.

Curr Opin Hematol. 2017 Nov 10;:

Authors: Kanariou M, Spanou K, Tantou S

Abstract
PURPOSE OF REVIEW: Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients.
RECENT FINDINGS: For years, CGD is a known cause of life-threatening infections and excessive inflammation. The cause and the management of inflammatory reactions, however, have not been clarified, and the range of clinical presentation is growing with corresponding novel therapeutic interventions. Recent work focuses on the best outcome of hematopoietic stem cell transplantation (HSCT) and gene therapy for the cure of CGD patients, more specifically, those with X-linked and p47 mutations.
SUMMARY: The genetics and phenotype of CGD is well characterized; however, the underlying mechanisms, the treatment of its inflammatory manifestations and the cure of CGD is under further investigation.

PMID: 29135572 [PubMed – as supplied by publisher]

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Long term immune reconstitution after matched unrelated hematopoietic stem cell transplantation for immunodeficiency.

J Allergy Clin Immunol. 2017 Nov 08;:

Authors: Kim VH, Reid B, Atkinson A, Upton J, Grunebaum E, Roifman CM

PMID: 29128672 [PubMed – as supplied by publisher]

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Flow Cytometric Evaluation of Primary Immunodeficiencies.

Clin Lab Med. 2017 Dec;37(4):895-913

Authors: Boldt A, Bitar M, Sack U

Abstract
Primary immunodeficiency diseases are genetic disorders that mostly cause susceptibility to infections and are sometimes associated with autoimmune and malignant diseases. For early detection and management of these diseases, flow cytometric procedures allow an encompassing assessment of cellular phenotypes and cellular functions. State-of-the art cytometry is based today on 8- to 10-color staining and includes an assessment of lineage maturation and functional markers.

PMID: 29128075 [PubMed – in process]

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In vivo measurements of interindividual differences in DNA glycosylases and APE1 activities.

Proc Natl Acad Sci U S A. 2017 Nov 09;:

Authors: Chaim IA, Nagel ZD, Jordan JJ, Mazzucato P, Ngo LP, Samson LD

Abstract
The integrity of our DNA is challenged with at least 100,000 lesions per cell on a daily basis. Failure to repair DNA damage efficiently can lead to cancer, immunodeficiency, and neurodegenerative disease. Base excision repair (BER) recognizes and repairs minimally helix-distorting DNA base lesions induced by both endogenous and exogenous DNA damaging agents. Levels of BER-initiating DNA glycosylases can vary between individuals, suggesting that quantitating and understanding interindividual differences in DNA repair capacity (DRC) may enable us to predict and prevent disease in a personalized manner. However, population studies of BER capacity have been limited because most methods used to measure BER activity are cumbersome, time consuming and, for the most part, only allow for the analysis of one DNA glycosylase at a time. We have developed a fluorescence-based multiplex flow-cytometric host cell reactivation assay wherein the activity of several enzymes [four BER-initiating DNA glycosylases and the downstream processing apurinic/apyrimidinic endonuclease 1 (APE1)] can be tested simultaneously, at single-cell resolution, in vivo. Taking advantage of the transcriptional properties of several DNA lesions, we have engineered specific fluorescent reporter plasmids for quantitative measurements of 8-oxoguanine DNA glycosylase, alkyl-adenine DNA glycosylase, MutY DNA glycosylase, uracil DNA glycosylase, and APE1 activity. We have used these reporters to measure differences in BER capacity across a panel of cell lines collected from healthy individuals, and to generate mathematical models that predict cellular sensitivity to methylmethane sulfonate, H2O2, and 5-FU from DRC. Moreover, we demonstrate the suitability of these reporters to measure differences in DRC in multiple pathways using primary lymphocytes from two individuals.

PMID: 29122935 [PubMed – as supplied by publisher]

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The Clinical Utility of Measuring IgG Subclass Immunoglobulins During Immunological Investigation for Suspected Primary Antibody Deficiencies.

Lab Med. 2017 Nov 08;48(4):314-325

Authors: Parker AR, Skold M, Ramsden DB, Ocejo-Vinyals JG, López-Hoyos M, Harding S

Abstract
Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA. The measurement of IgG subclasses may also help determine a revaccination strategy for patients and support patient management. In certain circumstances, the measurement of IgG subclasses may be used to monitor a patient’s humoral immune system. In this review, we discuss the utility of measuring IgG subclass concentrations.

PMID: 29126302 [PubMed – in process]

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Mannose-binding lectin protein deficiency among patients with primary immunodeficiency disease receiving IVIG therapy.

Endocr Metab Immune Disord Drug Targets. 2017 Nov 07;:

Authors: Azizi G, Kiaee F, Tavakolinia N, Rafiemanesh H, Mohammadikhajehdehi S, Sharifi L, Yazdani R, Abolhassani H, Aghamohammadi A

Abstract
BACKGROUND: Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of the immune system are defective. Immunoglobulin replacement therapy is the mainstay of treatment for patients with impaired antibody production. However, recurrent infections would continue to occur in some patients due to the other high frequent concomitant defects such as mannose-binding lectin (MBL) deficiency.
METHODS: A total of 51 PID patients participated in this cross-sectional study. A detailed questionnaire was completed by patient’s interview for all patients to record demographic data, clinical and laboratory data. The levels of MBL were determined in the serums of patients by a sandwich enzyme-linked immunosorbent assay (ELISA) technique.
RESULTS: MBL deficiency was found in 29.4% of cases; 11.8% patients had mild, 3.9% patients had moderate and 13.7% patients had severe MBL deficiency. In patients with MBL deficiency, the rate of meningitis, sepsis, pneumonia, and otitis media were higher than patients with normal MBL levels. Immunoglobulin replacement therapy reduced the rate of infectious complications in PID patients; however, these reductions were more apparent in patients with normal MBL levels than patients with MBL deficiency.
CONCLUSION: Antibody deficient patients with a concomitant immune defect in MBL production have higher rates of recurrent infections despite receiving Immunoglobulin replacement therapy.

PMID: 29119939 [PubMed – as supplied by publisher]

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Neurological Manifestations of Primary Immunodeficiency Diseases.

Clin Pediatr (Phila). 2017 Nov 01;:9922817737083

Authors: Aydin ÖF, Anlar B

PMID: 29117743 [PubMed – as supplied by publisher]

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Newborn Screening for Primary Immunodeficiency Diseases: History, Current and Future Practice.

J Clin Immunol. 2017 Nov 08;:

Authors: King JR, Hammarström L

Abstract
The primary objective of population-based newborn screening is the early identification of asymptomatic infants with a range of severe diseases, for which effective treatment is available and where early diagnosis and intervention prevent serious sequelae. Primary immunodeficiency diseases (PID) are a heterogeneous group of inborn errors of immunity. Severe combined immunodeficiency (SCID) is one form of PID which is uniformly fatal without early, definitive therapy, and outcomes are significantly improved if infants are diagnosed and treated within the first few months of life. Screening for SCID using T cell receptor excision circle (TREC) analysis has been introduced in many countries worldwide. The utility of additional screening with kappa recombining excision circles (KREC) has also been described, enabling identification of infants with severe forms of PID manifested by T and B cell lymphopenia. Here, we review the early origins of newborn screening and the evolution of screening methodologies. We discuss current strategies employed in newborn screening programs for PID, including TREC and TREC/KREC-based screening, and consider the potential future role of protein-based assays, targeted sequencing, and next generation sequencing (NGS) technologies, including whole genome sequencing (WGS).

PMID: 29116556 [PubMed – as supplied by publisher]

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