Research

Prevalence of Cryptosporidium Carriage and Disease in Children with Primary Immune-Deficiencies Undergoing Hematopoietic Stem Cell Transplant in Northern Europe.

Pediatr Infect Dis J. 2016 Dec 27;:

Authors: Davies AP, Slatter M, Gennery AR, Robinson G, Crouch N, Elwin K, Hadfield SJ, Cant AJ, Davies EG, Chalmers RM

Abstract
A prospective cohort study of children with primary immunodeficiencies undergoing hematopoietic stem cell transplant (HSCT) in the UK investigated the extent and significance of Cryptosporidium carriage in this high-risk group. Three of 42 children recruited were infected with Cryptosporidium, a lower proportion than previously described. One had serious disease. The underlying immunodeficiency likely had a bearing on the clinical presentation and possible outcome of infection.

PMID: 28030522 [PubMed – as supplied by publisher]

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Targeted busulfan and fludarabine-based conditioning for bone marrow transplantation in chronic granulomatous disease.

Korean J Pediatr. 2016 Nov;59(Suppl 1):S57-S59

Authors: Ju HY, Kang HJ, Hong CR, Lee JW, Kim H, Song SH, Yu KS, Jang IJ, Park JD, Park KD, Shin HY, Kim JG, Ahn HS

Abstract
Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days -8 to -5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m(2)) was administered once daily for 6 consecutive days from days -8 to -3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days -4 to -2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.

PMID: 28018447 [PubMed]

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Costs associated with treatment of severe combined immunodeficiency (SCID) – rationale for newborn screening in Sweden.

J Allergy Clin Immunol. 2016 Dec 21;:

Authors: Gardulf A, Winiarski J, Thorin M, Heibert Arnlind M, von Döbeln U, Hammarström L

PMID: 28012934 [PubMed – as supplied by publisher]

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Mucosal-associated invariant T cells are depleted and functionally altered in patients with common variable immunodeficiency.

Clin Immunol. 2016 Dec 20;:

Authors: Arduini S, Dunne J, Conlon N, Feighery C, Doherty DG

Abstract
Common variable immunodeficiency (CVID) is a primary immunoglobulin deficiency characterized by recurrent infections and complications, including autoimmunity, enteropathy, polyclonal lymphocytic infiltration or lymphoid malignancy. Innate T cells can support B cell maturation and antibody production. We investigated the numbers, phenotypes and functions of circulating B cell, γδ T cell, invariant natural killer T (iNKT) cell and mucosal-associated invariant T (MAIT) cell subsets in 23 CVID patients and 27 healthy controls. Switched-memory B cells and plasmablasts were depleted in CVID patients (p<0.0001). γδ T cells were found at normal numbers, but iNKT and MAIT cells were depleted (p<0.0001 and p<0.002). MAIT cells were especially low in patients with complicated CVID (p<0.05). MAIT cells from patients appeared more activated and more frequently produced interleukin-17A, interleukin-22 and tumor necrosis factor-α than MAIT cells from healthy subjects in vitro. Thus, MAIT cells depletion and activation may contribute to immunodeficiency and complications associated with CVID.

PMID: 28011187 [PubMed – as supplied by publisher]

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[Common variable immunodeficiency in adults].

Ter Arkh. 2016;88(11):94-98

Authors: Shabashova NV, Filippova LV, Uchevatkina AE, Frolova EV

Abstract
The paper analyzes 7 cases of common variable immune deficiency (CVID), a primary immunodeficiency disease. All the cases were detected in outpatients over the age of 40 years. The diagnosis was based on their history data and general clinical findings with due regard for the results of previously conducted functional studies, expert opinions, and the results of immunological studies including the quantitative and functional indices of T and B cells, phagocytes and the levels of immunoglobulins. The analysis showed that the early signs of impaired immunity in all the patients were seen by physicians of various specialties in both outpatient and inpatient settings. Generalizing of all information about the patient could become the basis for a simple and accessible practical public-health study of immunoglobulins levels significantly sooner than this diagnosis being verified. This testifies that the physicians of various specialties are partially aware of the clinical signs of immunodeficiency states and that there is a need for a clinical immunologist in adult healthcare facilities. This is especially important since the early clinical manifestations of both primary immunodeficiency disorders that are increasingly frequently detected and nonhereditary – secondary ones can be very similar. The timely verification of the diagnosis is necessary for prescribing adequate therapy with intravenous immunoglobulins to prevent severe chronic pyoinflammatory lung disease and disability in patients with CVID.

PMID: 28005038 [PubMed – in process]

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When to initiate immunoglobulin replacement therapy (IGRT) in antibody deficiency – a practical approach.

Clin Exp Immunol. 2016 Dec 21;:

Authors: Jolles S, Chapel H, Litzman J

Abstract
Primary antibody deficiencies (PAD) constitute the majority of all primary immunodeficiency diseases (PID) and immunoglobulin replacement forms the mainstay of therapy for many patients in this category. Secondary antibody deficiencies (SAD) represents a larger and expanding number of patients resulting from the use of a wide range of immunosuppressive therapies, in particular those targeting B cells, and may also result from renal or gastrointestinal immunoglobulin losses. While there are clear similarities between primary and secondary antibody deficiencies, there are also significant differences. This review describes a practical approach to the clinical, laboratory and radiological assessment of patients with antibody deficiency, focusing on the factors that determine whether immunoglobulin replacement should be used. The decision to treat is more straightforward when defined diagnostic criteria for some of the major PAD’s, such as common variable immunodeficiency disorders (CVID) or X-linked agammaglobulinaemia (XLA), are fulfilled or indeed when there is a very low level of immunoglobulin production in association with an increased frequency of severe or recurrent infections in SAD. However, the presentation of many patients is less clear cut and represents a considerable challenge in terms of the decision whether or not to treat and the best way in which to assess the outcome of therapy. This decision is important, not least to improve individual quality of life and reduce the morbidity and mortality associated with recurrent infections but also to avoid inappropriate exposure to blood products and to ensure immunoglobulin, a costly and limited resource, is used to maximal benefit. This article is protected by copyright. All rights reserved.

PMID: 28000208 [PubMed – as supplied by publisher]

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A novel mutation of WAS gene in a boy with Mycobacterium bovis infection at spleen.

Asian Pac J Allergy Immunol. 2016 Dec 12;:

Authors: Pacharn P, Boonyawat B, Tantemsapya N, Visitsunthorn N, Jirapongsananuruk O

Abstract
Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by mutations of the gene encoding WAS protein (WASp). A scoring system has been used to grade severity of the disease. However, the phenotype of the disease may progress over time, especially in children younger than 2 years of age. Here, we report a male child who presented with X-linked thrombocytopenia (XLT). Mutation analysis revealed a novel hemizygous 13-bp deletion (c.181_193delGCTGAGCACTGGA) on exon 2 of the WAS gene. This frameshift mutation resulted in a premature terminating codon at position 71 (p.A61fsX10). Molecular analysis of maternal DNA revealed a heterozygosity of the same mutation. The disease progressed to classic WAS within 8 months. Later, gastric varices as a consequence of Mycobacterium bovis infection at the spleen was detected. The rapid worsening of the disease may be due to the severe genotype of this patient.

PMID: 27996282 [PubMed – as supplied by publisher]

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Genetic Causes of Human NK Cell Deficiency and Their Effect on NK Cell Subsets.

Front Immunol. 2016;7:545

Authors: Mace EM, Orange JS

Abstract
Human NK cells play critical roles in human host defense, particularly the control of viral infection and malignancy, and patients with congenital immunodeficiency affecting NK cell function or number can suffer from severe illness. The importance of NK cell function is particularly underscored in patients with primary immunodeficiency in which NK cells are the primary or sole affected population (NK cell deficiency, NKD). While NKD may lead to the absence of NK cells, we are also gaining an increasing appreciation of the effect that NKD may have on the generation of specific NK cell subsets. In turn, this leads to improved insights into the requirements for human NK cell subset generation, as well as their importance in immune homeostasis. The presence of inherently abnormally developed or functionally impaired NK cells, in particular, appears to be problematic in the way of interfering with normal human host defense and may be more impactful than low numbers of NK cells alone. Here, we review the known genetic causes of NKD and the insight that is derived by these into the requirements for human subset generation and, by extension, for NK cell-mediated immunity.

PMID: 27994588 [PubMed]

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