Manish Butte

[Working together to improve the quality of life for people with primary immunodeficiencies: World PI Week 2013].

Rev Alerg Mex. 2013 Jan-Mar;60(1):1-4

Authors: Sorensen R, Etzioni A, Aziz A, Zeiger JB

PMID: 24008062 [PubMed – indexed for MEDLINE]

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Noninfectious Cutaneous Granulomas in Primary Immunodeficiency Disorders: Report From a National Registry.

Am J Dermatopathol. 2014 Jul 24;

Authors: Nanda A, Al-Herz W, Al-Sabah H, Al-Ajmi H

Abstract
: The association of noninfectious cutaneous granulomas with primary immunodeficiency disorders (PIDs) is a rare but well-recognized phenomenon. With the recent advent of new classification and broadening of the list of PIDs, there is now ever-growing number of PIDs having being reported with noninfectious cutaneous granulomas or granulomatous tissue reactions. The authors observed 4 patients with cutaneous granulomas associated with PIDs that constitute 2% of total PIDs registered with them. In this report, the authors describe these 4 patients with cutaneous granulomas/granulomatous skin reactions associated one each with common variable immunodeficiency, Omenn syndrome, combined immunodeficiency, and Blau syndrome (BS), and briefly review the literature on various clinicopathological patterns of cutaneous granulomas with possible underlying pathogenetic mechanisms responsible for such tissue reactions in patients with PID.

PMID: 25062261 [PubMed – as supplied by publisher]

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Consanguinity and polygenic diseases: a model for antibody deficiencies.

Hum Hered. 2014;77(1-4):144-9

Authors: Di Pierro V, Zuntini R, Cancrini C, Finocchi A, Angelino G, Rossi P, Ferrari S

Abstract
Primary immunodeficiencies represent a heterogeneous group of disorders of the immune system, predisposing to various types of infections. Among them, common variable immunodeficiency is the most common symptomatic antibody deficiency. It includes several different forms characterized by defects in the terminal stage of B lymphocyte differentiation, leading to markedly reduced immunoglobulin serum levels and increased susceptibility to bacterial infections. The clinical phenotype is complex, including autoimmunity, granulomatous inflammation, lymphoproliferative disorders and malignancies. Rare autosomal recessive mutations in a number of single genes have recently been reported. However, the underlying genetic defects remain unknown in the majority of cases. In order to seek new genes responsible for the disease, we studied a consanguineous Italian family through exome sequencing combined with homozygosity mapping. Six missense homozygous variants passed our filtering selection and at least two of them were associated with some aspects of the pathological phenotype. Our data remark the complexity of immune system disorders and emphasize the difficulty to understand the significance of genetic results and their correlation with the disease phenotype. © 2014 S. Karger AG, Basel.

PMID: 25060277 [PubMed – in process]

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Three difficult cases: the challenge of autoimmunity, immunodeficiency and recurrent infections in patients with Good’s syndrome.

Br J Dermatol. 2014 Jul 24;

Authors: Arnold SJ, Hodgson T, Misbah SA, Patel SY, Cooper SM, Venning VA

Abstract
Good’s syndrome is a rare, adult-acquired primary combined immunodeficiency syndrome arising in the context of previous or current thymoma. Patients with Good’s syndrome frequently develop recurrent sinopulmonary infections and are also at high risk of autoimmune manifestations including skin conditions such as lichen planus. We report three cases of middle-aged patients with Good’s syndrome complicated by multiple autoimmune and infectious manifestations. The combination of immunodeficiency, autoimmunity and recurrent infections seen in patients with Good’s syndrome continues to present a management challenge, particularly in patients with oral mucosal disease and recurrent candidiasis. Clinicians should be prompted to investigate an underlying immunodeficiency in patients with multiple autoimmune conditions and recurrent sinopulmonary infections. This article is protected by copyright. All rights reserved.

PMID: 25059810 [PubMed – as supplied by publisher]

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Inherited CARD9 deficiency in two unrelated patients with invasive Exophiala infection.

J Infect Dis. 2014 Jul 23;

Authors: Lanternier F, Barbati E, Meinzer U, Liu L, Pedergnana V, Migaud M, Héritier S, Chomton M, Frémond ML, Gonzales E, Galeotti C, Romana S, Jacquemin E, Angoulvant A, Bidault V, Canioni D, Lachenaud J, Mansouri D, Mahdaviani SA, Adimi P, Mansouri N, Jamshidi M, Bougnoux ME, Abel L, Lortholary O, Blanche S, Casanova JL, Picard C, Puel A

Abstract
BACKGROUND:  Exophiala spp. are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare, with 42 cases reported and frequently fatal infection. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only three cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida spp., dermatophytes or Phialophora verrucosa.
METHODS:  We investigated (i) an eight-year-old girl born in France, from a non-consanguineous Angolan kindred, who developed disseminated Exophiala dermatitidis disease, and (ii) a 26 year-old woman, from an Iranian consanguineous kindred living in Iran, who developed disseminated Exophiala spinifera disease. Both patients were otherwise healthy.
RESULTS:  We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18 W and E323del). The first patient had segmental uniparental disomy (UPD) of chromosome 9, carrying two copies of the maternal CARD9 mutated allele.
CONCLUSIONS:  These two patients are the first with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala spp. disease, even in the absence of other infections.

PMID: 25057046 [PubMed – as supplied by publisher]

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Vaccine-Associated Varicella and Rubella Infections In Severe Combined Immunodeficiency with Isolated CD4 Lymphocytopenia and Mutations in IL7R Detected by Tandem Whole Exome Sequencing and Chromosomal Microarray.

Clin Exp Immunol. 2014 Jul 21;

Authors: Bayer D, Martinez C, Sorte H, Forbes L, Demmler-Harrison G, Hanson I, Pearson N, Noroski L, Bellini W, Leduc M, Yang Y, Eng C, Patel A, Rodningen O, Muzny D, Gibbs R, Campell I, Baker M, Zhang V, Lupski J, Orange J, Seeborg F, Stray-Pedersen A

Abstract
In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and not identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunologic evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, presence of CD8+ T cells, poor lymphocyte proliferation, hypergammaglobulinemia, and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pre-transplant blood and buccal DNA, and maternal engraftment (5-10%) demonstrated in pre-transplant blood DNA. This may be responsible for the patient’s unusual immunologic phenotype compared to classical IL7Ralpha deficiency. Disseminated VZV was controlled with antiviral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T-cell receptor excision circles (TREC) analyses completed on neonatal Guthrie cards from the patient identified absent TRECs. This case emphasizes the danger of live viral vaccination in SCID patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality, and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic etiology for SCID patients.

PMID: 25046553 [PubMed – as supplied by publisher]

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A rare pigmentary disorder in two non-identical siblings: Griscelli Syndrome -type 3.

Dermatol Online J. 2014;20(7)

Authors: Kaur S, Jindal N, Dayal S, Jain VK, Jairath V, Virdi S

Abstract
Griscelli Syndrome (GS) is a rare autosomal recessive disorder characterized by pigmentary dilution of the hair and skin (partial albinism). Three different types (1-3) caused by mutation in three different genes have been described. Patients with GS type 1 have primary central nervous system dysfunction; type 2 patients commonly develop hemophagocytic lymphohistiocytosis and type 3 patients present with partial albinism only. Two siblings discussed here had silvery hair, eyebrows and eyelashes since birth with no features suggestive of immunodeficiency or neurological impairment, making it an even rarer presentation of Griscelli Syndrome, type 3. Diagnosis was confirmed on light microscopy (LM) of hair shafts. Both GS1 and GS2 have been described earlier. However, extensive search of the literature failed to reveal a similar presentation from Indian origin. This is the first ever report of GS-3 in non-identical siblings from India.

PMID: 25046460 [PubMed – as supplied by publisher]

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Clinical and molecular characteristics of Chinese patients with X-linked lymphoproliferative syndrome type 1.

Pediatr Blood Cancer. 2014 Jul 15;

Authors: An YF, Luo XB, Yang X, Wang J, Li L, Zhao XD

Abstract
BACKGROUND: X-linked lymphoproliferative syndrome type 1 (XLP1) is a rare inherited, life-threatening immunodeficiency disorder caused by mutations in SH2D1A gene. It affect approximately two to three males per million. Fewer than 10 cases with definite gene mutations have been reported in Chinese mainland and no rapid diagnosis method has been established.
PROCEDURE: We determined the clinical and molecular characteristics of five patients with XLP1. The SH2D1A gene were amplified by PCR and sequenced, the SAP expression was analyzed by flow cytometry.
RESULTS: Two patients had novel SH2D1A mutations and three had mutations that have been previously reported. Three patients presented with fulminant infectious mononucleosis or hemophagocytic lymphohistiocytosis and one presented with lymphoma. Null or decreased SAP expression on PBMCs was noted. The remaining patient presented with unique, recurrent, nonfulminant infectious mononucleosis and bimodal intracellular SAP protein expression.
CONCLUSIONS: The overall molecular characteristics and clinical phenotypes of Chinese patients with XLP1 matched previous reports. The unique bimodal intracellular SAP protein expression indicated the presence of some residual SAP-positive T cells that are able to respond to persistent Epstein-Barr virus infection and could explain the relatively mild clinical phenotype of this patient. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

PMID: 25044636 [PubMed – as supplied by publisher]

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Circulating endothelial cells as markers of endothelial dysfunction during hematopoietic stem cell transplantation for pediatric primary immunodeficiency.

J Allergy Clin Immunol. 2014 Jul 16;

Authors: Touzot F, Moshous D, Cros G, Frange P, Chomton M, Frémond ML, Neven B, Cavazzana M, Fischer A, Blanche S, Helley D

PMID: 25042984 [PubMed – as supplied by publisher]

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Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): Chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding.

J Allergy Clin Immunol. 2014 Jul 18;

Authors: Frans G, Moens L, Schaballie H, Van Eyck L, Borgers H, Wuyts M, Dillaerts D, Vermeulen E, Dooley J, Grimbacher B, Cant A, Declerck D, Peumans M, Renard M, De Boeck K, Hoffman I, François I, Liston A, Claessens F, Bossuyt X, Meyts I

PMID: 25042743 [PubMed – as supplied by publisher]

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