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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]

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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]

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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]

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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]

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Melioidosis in children: a retrospective study.

Int J Dermatol. 2015 Mar 13;

Authors: Foong YW, Tan NW, Chong CY, Thoon KC, Tee NW, Koh MJ

Abstract
BACKGROUND: Melioidosis, caused by Burkholderia pseudomallei, is endemic in Singapore and can present as localized or disseminated disease.
METHODS: Demographic data, clinical features, investigation results, treatments, and outcomes in patients aged <16 years diagnosed with melioidosis at KK Women’s and Children’s Hospital between January 2002 and January 2014 were retrospectively reviewed. Data for patients with primary skin disease and those with other organ involvement were compared.
RESULTS: Seventeen children were diagnosed with melioidosis. Their median age was 12.5 years (range: 2-15 years). Nine (53%) patients presented with localized cutaneous melioidosis and five (29%) with localized lymphadenitis, pneumonia, or septic arthritis. The remaining three (18%) patients had melioidosis sepsis; two of these patients died from septic shock. Treatment included an initial 1-2 weeks of IV antibiotics followed by 3-6 months of oral combination antibiotics. All cases of localized cutaneous disease resolved completely with no recurrences. Three (60%) of the five patients with localized involvement of other organ systems achieved complete resolution of disease, and the remaining two were lost from follow-up.
CONCLUSIONS: Although uncommon, melioidosis can occur in children living in endemic regions. Patients with localized skin disease have good outcomes with no recurrences. Systemic disease can be fatal, especially in the presence of underlying immunodeficiency. Diagnosis requires a high index of suspicion, and treatment requires prolonged combination antibiotic therapy.

PMID: 25771733 [PubMed – as supplied by publisher]

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Related Articles

[Primary immunodeficiencies are a topical problem of modern medicine].

Ter Arkh. 2014;86(11):12-5

Authors: Troitskaya EV, Sofronova LV, Tsvetkova TY

Abstract
AIM: To analyze the incidence of primary immunodeficiencies (PIDs), to reveal the specific features of the course of this condition at the present stage, and to estimate the quality of health care to patients with PIDs.
SUBJECTS AND METHODS: An open-label prospective trial was performed in 94 patients with different forms of PIDs (63 with selective immunoglobulin A (IgA) deficiency and 31 with other more severe primary immunodeficiencies) who had been permanent residents in the Perm Territory in the period 1990 to 2012.
RESULTS: The registered PID cases were noted to be lower than the estimated ones. Over 22 years of follow-ups, the death rates for this group of patients with these diseases were 11%, and the disability rates were 27%. In severe PIDs (exclusive of selective IgA deficiency), these rates were as high as 35.5 and 96%, respectively. The rate of untimely diagnosis of severe PIDs was high (43%). Molecular genetic studies were conducted in only one tenth of the patents with this disease. PID treatment generally complied with the accepted medical standards. However, all patients with X-linked agammaglobulinemia were observed to have periodic irregularities of replacement therapy with intravenous immunoglobulins, which was a cause of death in 2 patients. Adult patients with common variable immune deficiency received no adequate replacement therapy. Timely diagnosis and adequate therapy could not only preserve the life of many patients with severe PIDs (64.5% survived), but could achieve its relatively satisfactory quality.
CONCLUSION: As of now, PIDs ceased to be fatal diseases. To improve the quality of health care to patients with this pathology, there is a need to increase the awareness of the diagnosis and treatment of immunodeficiencies among physicians of different specialties, to extend the application of molecular genetic techniques, including those for prenatal diagnosis, and to continuously provide patients with essential drugs.

PMID: 25715480 [PubMed – indexed for MEDLINE]

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Rare mendelian primary immunodeficiency diseases associated with impaired NF-κB signaling.

Genes Immun. 2015 Mar 12;

Authors: Paciolla M, Pescatore A, Conte MI, Esposito E, Incoronato M, Lioi MB, Fusco F, Ursini MV

Abstract
Mendelian primary immunodeficiency diseases (MPIDs) are rare disorders affecting distinct constituents of the innate and adaptive immune system. Although they are genetically heterogeneous, a substantial group of MPIDs is due to mutations in genes affecting the nuclear factor-κB (NF-κB) transcription pathway, essential for cell proliferation and cell survival and involved in innate immunity and inflammation. Many of these genes encode for crucial regulatory components of the NF-κB pathway and their mutations are associated with immunological and developmental signs somehow overlapping in patients with MPIDs. At present, nine different MPIDs listed in the online mendelian inheritance in man (OMIM) are caused by mutations in at least nine different genes strictly involved in the NF-κB pathway that result in defects in immune responses. Here we report on the distinct function of each causative gene, on the impaired NF-κB step and more in general on the molecular mechanisms underlining the pathogenesis of the disease. Overall, the MPIDs affecting the NF-κB signalosome require a careful integrated diagnosis and appropriate genetic tests to be molecularly identified. Their discovery at an ever-increasing rate will help establish a common therapeutic strategy for a subclass of immunodeficient patients.Genes and Immunity advance online publication, 12 March 2015; doi:10.1038/gene.2015.3.

PMID: 25764117 [PubMed – as supplied by publisher]

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HkRP3 Is a Microtubule-Binding Protein Regulating Lytic Granule Clustering and NK Cell Killing.

J Immunol. 2015 Mar 11;

Authors: Ham H, Huynh W, Schoon RA, Vale RD, Billadeau DD

Abstract
NK cells provide host defense by killing viral-infected and cancerous cells through the secretion of preformed lytic granules. Polarization of the lytic granules toward the target cell is dependent on an intact microtubule (MT) network as well as MT motors. We have recently shown that DOCK8, a gene mutated in a primary immunodeficiency syndrome, is involved in NK cell killing in part through its effects on MT organizing center (MTOC) polarization. In this study, we identified Hook-related protein 3 (HkRP3) as a novel DOCK8- and MT-binding protein. We further show that HkRP3 is present in lytic granule fractions and interacts with the dynein motor complex and MTs. Significantly, depletion of HkPR3 impaired NK cell cytotoxicity, which could be attributed to a defect in not only MTOC polarity, but also impaired clustering of lytic granules around the MTOC. Our results demonstrate an important role for HkRP3 in regulating the clustering of lytic granules and MTOC repositioning during the development of NK cell-mediated killing.

PMID: 25762780 [PubMed – as supplied by publisher]

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Successful Newborn Screening for SCID in the Navajo Nation.

Clin Immunol. 2015 Mar 8;

Authors: Kwan A, Hu D, Song M, Gomes H, Brown DR, Bourque T, Gonzalez-Espinosa D, Lin Z, Cowan MJ, Puck JM

Abstract
Newborn screening (NBS) for severe combined immunodeficiency (SCID) identifies affected infants before the onset of life-threatening infections, permitting optimal treatment. Navajo Native Americans have a founder mutation in the DNA repair enzyme Artemis, resulting in frequent Artemis SCID (SCID-A). A pilot study at 2 Navajo hospitals assessed the feasibility of SCID NBS in this population. Dried blood spots from 1,800 infants were assayed by PCR for T-cell receptor excision circles (TRECs), a biomarker for naïve T cells. Starting in February 2012, TREC testing transitioned to standard care throughout the Navajo Area Indian Health Service, and a total of 7,900 infants were screened through July 2014. One infant had low TRECs and was diagnosed with non-SCID T lymphopenia, while 4 had undetectable TRECs due to SCID-A, all of whom were referred for hematopoietic cell transplantation. This report establishes the incidence of SCID-A and demonstrates effectiveness of TREC NBS in the Navajo.

PMID: 25762520 [PubMed – as supplied by publisher]

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Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency.

Clin Exp Immunol. 2015 Mar 11;

Authors: Niebur HB, Duff CM, Shear GF, Nguyen D, Alberdi TK, Dorsey MJ, Sleasman JW

Abstract
PURPOSE: Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). Efficacy and tolerability of 16% SCIG (Vivaglobin®) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects.
METHODS: The study was a prospective, single-center, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included IgG levels; tetanus, varicella, and S pneumoniae titers; adverse events (AEs), annual infection rate, and quality of life over 8 weeks of Vivaglobin and 24 weeks of Hizentra.
RESULTS: 32 subjects (2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in 12.8% (±2.9%) increase in SCIG dose. Median IgG level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 vs 1035mg/dL, respectively; P=0.77). Both products had similar protective titers to tetanus, varicella, and serotypes of S. pneumoniae which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104.7 minutes (3.3 sites) with Vivaglobin to 70.7 minutes (2.2 sites) with Hizentra (P=0.0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra.
CONCLUSIONS: Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well-tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. This article is protected by copyright. All rights reserved.

PMID: 25761372 [PubMed – as supplied by publisher]

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