Research

Efficacy and Safety of Hospital-Based Intravenous Immunoglobulin and Home-Based Self-Administered Subcutaneous Immunoglobulin in Polish Children with Primary Immunodeficiency Diseases.

Indian J Pediatr. 2015 Mar 19;

Authors: Bal K, Kałuzińska-Parzyszek I, Sobocińska A, Podlecka D, Jerzyńska J, Stelmach I

PMID: 25786586 [PubMed – as supplied by publisher]

Powered by WPeMatico

Primary Immunodeficiency Diseases: An Opportunity in Pediatrics for Improving Patient Outcomes.

Clin Pediatr (Phila). 2015 Mar 15;

Authors: Hernandez-Trujillo VP, Scalchunes C, Hernandez-Trujillo HS, Boyle J, Williams P, Boyle M, Orange JS

Abstract
OBJECTIVES: Primary immunodeficiency diseases (PIDDs) are caused by inherent deficits in immune defenses that result in abnormal susceptibility to infection. In most cases, early and appropriate diagnosis can improve patient outcomes. The objective of this study was to evaluate understanding, recognition, and diagnosis of PIDD among pediatricians.
METHODS: A mail survey sent to a sample of pediatricians obtained from the American Medical Association and American Osteopathic Association. Results were compared with a similar survey of specialists who are members of the American Academy of Asthma, Allergy and Immunology.
RESULTS: More than a third (35%) of pediatricians were uncomfortable with the recognition and diagnosis of PIDD despite 95% having ordered screening tests or referring patients to specialists to be evaluated for PIDD, and 77% having followed at leastone patient with PIDD. In all, 84% of pediatricians were unaware that professional guidelines for PIDD exist.
CONCLUSIONS: Patients with PIDD would benefit from improved recognition of the diseases by pediatricians in order to facilitate earlier diagnosis and optimize ongoing therapy.

PMID: 25780256 [PubMed – as supplied by publisher]

Powered by WPeMatico

The Diagnosis of Hyper Immunoglobulin E Syndrome Based on Project Management.

Iran J Allergy Asthma Immunol. 2015 Apr;14(2):126-132

Authors: Saghafi S, Pourpak Z, Glocker C, Nussbaumer F, Babamahmoodi A, Grimbacher B, Moin M

Abstract
Hyperimmunoglobulin E Syndrome (HIES) is a complex primary immunodeficiency characterized by both immunologic and non-immunologic manifestations. High serum IgE level, eosinophilia, eczema, recurrent skin and lung infections constitute the immunologic profile of HIES, whereas characteristic facial appearance, scoliosis, retained primary teeth, joint hyperextensibility, bone fractures following minimal trauma and craniosynostosis are the main non-immunologic manifestations. The diagnosis of HIES cannot be made by routine immunologic tests. As the main characteristic laboratory abnormalities of this syndrome are highly elevated serum IgE levels and eosinophilia; both features have a broad spectrum of differential diagnosis. The purpose of this essay was presenting the best way for diagnosis management of HIES. Based on the genetic reports of patients of the Center for Chronic Immunodeficiency (CCI) as a single center experience, and applying project management (PM) in health care research projects, we sought the best way for a rapid diagnosis of HIES. The combination of project management principles with immunologic and genetic knowledge to better define the laboratory and clinical diagnosis lead to an improvement of the management of patients with HIES. These results are shown in one “Decision Tree” which is based on 342 genetic reports of the CCI during the past ten years. It is necessary to facilitate the diagnostic analysis of suspected HIES patients; applying project management in health care research projects provides a better and more accurate diagnosis eventually leading to a better patients’ care. This Abstract was presented at 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), Prague, Czech Republic.

PMID: 25780878 [PubMed – as supplied by publisher]

Powered by WPeMatico

Delayed control of herpes simplex virus infection and impaired CD4(+) T-cell migration to the skin in mouse models of DOCK8 deficiency.

Immunol Cell Biol. 2015 Mar 17;

Authors: Flesch IE, Randall KL, Hollett NA, Di Law H, Miosge LA, Sontani Y, Goodnow CC, Tscharke DC

Abstract
DOCK8 deficiency in humans and mice leads to multiple defects in immune cell numbers and function. Patients with this immunodeficiency have a high morbidity and mortality, and are distinguished by chronic cutaneous viral infections, including those caused by herpes simplex virus (HSV). The underlying mechanism of the specific susceptibility to these chronic cutaneous viral infections is currently unknown, largely because the effect of DOCK8 deficiency has not been studied in suitable models. A better understanding of these mechanisms is required to underpin the development of more specific therapies. Here we show that DOCK8-deficient mice have poor control of primary cutaneous herpes simplex lesions and this is associated with increased virus loads. Furthermore, DOCK8-deficient mice showed a lack of CD4(+) T-cell infiltration into HSV-infected skin.Immunology and Cell Biology advance online publication, 17 March 2015; doi:10.1038/icb.2015.32.

PMID: 25776845 [PubMed – as supplied by publisher]

Powered by WPeMatico

[Mosaic forms of ataxia-telangiectasia].

Tsitologiia. 2014;56(8):619-29

Authors: Kuranova ML, Pleskach NM, Ledashcheva TA, Mikhel’son VM, Spivak IM

Abstract
Ataxia-telangiectasia (AT) is a severe hereditary autosomal recessive neurodegenerative disease associated with accelerated aging and caused by mutation in both alleles of atm gene. This gene encodes a key protein of cell response to DNA damage–an ATM protein kinase. Normally, upon formation of DNA double strand breaks ATM is autophosphorylated and its active form phospho-ATM (P-ATM) appears. Here we describe a mosaic form of AT in which cells of the same patient with normal atm gene demonstrated the accumulation of P-ATM in response to DNA double-strand breaks-inducing factors whereas in cells bearing a mutant form of atm P-ATM was not detected. The epigenetic markers such as histone deacetylases SIRT1 and SIRT6, and trimethylated forms of histone H3 – H3K9me3 and H3K27me3–were studied in the nuclei of primary fibroblasts derived from patients with different forms of AT and the increase of SIRT6 level was revealed.

PMID: 25697008 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Related Articles

Subcutaneous immunoglobulin loading regimens for previously untreated patients with primary antibody deficiency.

Clin Exp Immunol. 2014 Dec;178 Suppl 1:146-8

Authors: Rojavin M, Sidhu J, Pfister M, Hubsch A

PMID: 25546799 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Related Articles

Europe immunoglobulin map.

Clin Exp Immunol. 2014 Dec;178 Suppl 1:141-3

Authors: Šedivá A, Chapel H, Gardulf A, European Immunoglobulin Map Group (35 European Countries) for European Society for Immunodeficiencies (ESID) Primary Immunodeficiencies Care in Development Working Party

PMID: 25546797 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Unraveling the Link Between Ectodermal Disorders and Primary Immunodeficiencies.

Int Rev Immunol. 2015 Mar 16;

Authors: D’Assante R, Fusco A, Palamaro L, Giardino G, Gallo V, Cirillo E, Pignata C

Abstract
Primary immunodeficiencies (PIDs) include a heterogeneous group of mostly monogenic diseases characterized by functional/developmental alterations of the immune system. Skin and skin annexa abnormalities may be a warning sign of immunodeficiency, since both epidermal and thymic epithelium have ectodermal origin. In this review, we will focus on the most common immune disorders associated with ectodermal alterations. Elevated IgE levels represent the immunological hallmark of hyper-IgE syndrome, characterized by severe eczema and susceptibility to infections. Ectodermal dysplasia (ED) is a group of rare disorders that affect tissues of ectodermal origin. Hypoidrotic ED (HED), the most common form, is inherited as autosomal dominant, autosomal recessive or X-linked trait (XLHED). HED and XLHED are caused by mutations in NEMO and EDA-1 genes, respectively, and show similarities in the cutaneous involvement but differences in the susceptibility to infections and immunological phenotype. Alterations in the transcription factor FOXN1 gene, expressed in the mature thymic and skin epithelia, are responsible for human and murine athymia and prevent the development of the T-cell compartment associated to ectodermal abnormalities such as alopecia and nail dystrophy. The association between developmental abnormalities of the skin and immunodeficiencies suggest a role of the skin as a primary lymphoid organ. Recently, it has been demonstrated that a co-culture of human skin-derived keratinocytes and fibroblasts, in the absence of thymic components, can support the survival of human haematopoietic stem cells and their differentiation into T-lineage committed cells.

PMID: 25774666 [PubMed – as supplied by publisher]

Powered by WPeMatico

Common Variable Immunodeficiency and Pulmonary Amyloidosis: A Case Report.

J Clin Immunol. 2015 Mar 14;

Authors: Arslan S, Ucar R, Yavsan DM, Esen H, Maden E, Reisli I, Calıskaner AZ

Abstract
Common variable immunodeficiency is the most common symptomatic primary immune deficiency characterized by hypogammaglobulinemia, recurrent infections, and increased risk of autoimmune disease and malignancy. Secondary amyloidosis develops from chronic inflammatory conditions. The co-existence of CVID (especially in patients with bronchiectasis) and secondary amyloidosis has been reported rarely. We describe the first case of pulmonary hypertension secondary to pulmonary amyloidosis in a patient with CVID.

PMID: 25773572 [PubMed – as supplied by publisher]

Powered by WPeMatico

Cutaneous granulomas in the setting of primary immunodeficiency: a report of four cases and review of the literature.

Int J Dermatol. 2015 Mar 13;

Authors: Harp J, Coggshall K, Ruben BS, Ramírez-Valle F, He SY, Berger TG

Abstract
IMPORTANCE: Cutaneous granulomas without an identifiable infectious etiology are a rare manifestation of primary immunodeficiency (ID). These cutaneous lesions can be misdiagnosed, often as sarcoidosis, when the skin findings precede the diagnosis of immunodeficiency.
OBJECTIVE: We present four cases from our institution and review the literature in order to emphasize the clinical relevance of this association, discuss the histologic and immunohistochemical features, and explore possible pathogenic mechanisms of granuloma formation.
EVIDENCE REVIEW: We retrospectively reviewed case reports of all patients presenting with cutaneous granulomas in the setting of primary immunodeficiency. Cases with insufficient information to confirm an immunodeficiency state were excluded. Four patients from our clinic were included, for 54 total cases.
FINDINGS: The majority of cutaneous granulomas are seen in three types of immunodeficiencies: ataxia-telangiectasia, severe combined immunodeficiency, and combined variable immunodeficiency. Twenty-six percent of patients developed cutaneous granulomas prior to their immunodeficiency diagnosis. Histologically, various granulomatous patterns have been described. Immunohistochemistry revealed a CD4+/CD8+ lymphocyte ratio of less than or equal to 1 in our four patients, which may help differentiate cutaneous granulomas in primary ID from sarcoidal granulomas that typically show a CD4+ predominance.
CONCLUSIONS AND RELEVANCE: Cutaneous granulomas are a rare manifestation of primary ID and occur predominantly in immunodeficiencies that affect T and B cell compartments.

PMID: 25773292 [PubMed – as supplied by publisher]

Powered by WPeMatico