Research

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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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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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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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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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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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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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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Relationship between hypogammaglobulinemia and severity of atopic dermatitis.

Ann Allergy Asthma Immunol. 2014 Jul 16;

Authors: Celiksoy MH, Topal E, Sancak R, Catal F, Sogut A

Abstract
BACKGROUND: Atopic dermatitis is an itchy, inflammatory, chronic, or chronically relapsing skin disease. The disease occurs in people who have an “atopic tendency” or may appear as a clinical sign of primary immunodeficiency.
OBJECTIVES: To determine the relation between severity of atopic dermatitis and hypogammaglobulinemia.
METHODS: One hundred sixty pediatric patients with atopic dermatitis (98 boys and 62 girls, 1-60 months old, median age 14.5 months) and 95 healthy children (57 boys and 38 girls, median age 16 months; control group) were included in the study. In patients with atopic dermatitis, the severity of disease was determined by the SCORing Atopic Dermatitis index. Serum immunoglobulin levels of all patients and children in the control group were measured by nephelometry on admission.
RESULTS: The incidence of hypogammaglobulinemia was higher in patients with atopic dermatitis than in the control group (P = .009). The main reason for this difference was the low level of IgG in the atopic dermatitis group (P = .024). Analysis of the relation between hypogammaglobulinemia and the severity of atopic dermatitis showed no statistically significant difference between the group with mild to moderate atopic dermatitis and the group with severe atopic dermatitis with respect to hypogammaglobulinemia (P = .859), IgG (P = .068), IgA (P = .410), and IgM (P = .776) values.
CONCLUSION: Hypogammaglobulinemia was more frequent in patients with atopic dermatitis compared with the control group, mostly owing to the low IgG level. Hypogammaglobulinemia is not associated with the severity of atopic dermatitis.

PMID: 25037609 [PubMed – as supplied by publisher]

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How should eosinophilic cystitis be treated in patients with chronic granulomatous disease?

Pediatr Nephrol. 2014 Jul 19;

Authors: Claps A, Della Corte M, Gerocarni Nappo S, Francalanci P, Palma P, Finocchi A

Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting from the absence or malfunction of oxidative mechanism in phagocytic cells. The disease is due to a mutation in one of four genes that encode subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Affected patients experience severe infections and granuloma formation due to exuberant inflammatory responses. Some evidence suggests that eosinophilic cystitis (EC) is included in the spectrum of inflammatory manifestations. EC is an inflammatory disease, rare in childhood, which may require different, nonstandardized therapeutic approaches, ranging from antihistamines to cyclosporine.
CASE-DIAGNOSIS/TREATMENT: Herein we describe the cases of two CGD patients with CGD who experienced EC during hospitalization for a severe infection.
CONCLUSIONS: EC in immunocompetent children seems to have a self-limiting course, unlike in CGD patients, in whom it presents a prolonged and recurrent course. We focus on the effective therapy administered to our patients with CGD and review the corresponding literature.

PMID: 25037864 [PubMed – as supplied by publisher]

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NK and B cell deficiency in a MPS type II family with novel mutation in the IDS gene.

Clin Immunol. 2014 Jul 16;

Authors: Torres LC, de Queiroz Soares DC, Kulikowski LD, Franco JF, Kim CA

Abstract
The mucopolysaccharidoses (MPSs) are a group of rare, inherited lysosomal storage disorders that are clinically characterized by abnormalities in multiple organ systems and reduced life expectancy. Whereas the lysosome is essential to the functioning of the immune system, some authors suggest that the MPS patients have abnormalities in the immune system similarly to patients with primary immunodeficiency. In this study, we evaluated 8 male MPS type II patients of a same family with novel mutation in the IDS gene. We found in this MPS family a quantitative deficiency of NK and B cells with normal values of IgG, IgM and IgA serum antibodies and normal response to polysaccharide antigens. Interestingly, abnormalities found in these patients were not observed in other MPSs patients, suggesting that the type of mutation found in the IDS gene can be implicated in the immunodeficiency.

PMID: 25038527 [PubMed – as supplied by publisher]

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