Manish Butte

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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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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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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Streptococcus pneumoniae serotype 6C presenting as recurrent prosthetic knee joint infection in a patient with a history of congenital asplenia and underlying autoimmune disease: a case report and literature review.

Diagn Microbiol Infect Dis. 2013 Dec;77(4):376-9

Authors: Roberts AL, Hewlett AL, Yu J, Nahm MH, Fey PD, Iwen PC

Abstract
This report describes a case of primary Streptococcus pneumoniae bacteremia with prosthetic joint infection caused by serotype 6C with recurrent infection in a patient with a history of congenital asplenia and underlying autoimmune disease. Isolates from the primary and recurrent infections were determined to be indistinguishable by pulsed-field gel electrophoresis. This study expands the conditions associated with recurrent invasive pneumococcal disease caused by serotype 6C.

PMID: 24139971 [PubMed – indexed for MEDLINE]

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Sequential asymptomatic enterovirus infections in a patient with MHC class II primary immunodeficiency.

J Clin Microbiol. 2014 Jul 16;

Authors: Driss N, Mellouli F, Ben Yahia A, Touzi H, Barbouche MR, Triki H, Bejaoui M

Abstract
Patients with primary immunodeficiencies are usually susceptible to enterovirus infections and have higher risks to develop severe clinical forms. We report a unique description of a boy with MHC-ClassII deficiency infected by 9 different enterovirus serotypes during a 2-years-period, with very mild clinical symptoms; probably due to the immunoglobulin therapy he was receiving.

PMID: 25031436 [PubMed – as supplied by publisher]

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Selective demethylation and altered gene expression are associated with ICF Syndrome in human induced pluripotent stem cells and mesenchymal stem cells.

Hum Mol Genet. 2014 Jul 15;

Authors: Huang K, Wu Z, Liu Z, Hu G, Yu J, Chang KH, Kim KP, Le T, Faull KF, Rao N, Gennery A, Xue Z, Wang CY, Pellegrini M, Fan G

Abstract
Immunodeficiency, Centromeric Instability, and Facial Anomalies Type I (ICF1) Syndrome is a rare genetic disease caused by mutations in DNMT3B, a de novo DNA methyltransferase. However, the molecular basis of how DNMT3B-deficiency leads to ICF1 pathogenesis is unclear. Induced pluripotent stem cell (iPSC) technology facilitates the study of early human developmental diseases via facile in vitro paradigms. Here, we generate iPSCs from ICF Type 1 Syndrome patient fibroblasts followed by directed differentiation of ICF1-iPSCs to mesenchymal stem cells (MSCs). By performing genome-scale bisulfite sequencing, we find that DNMT3B-deficient iPSCs exhibit global loss of non-CG methylation and select CG hypomethylation at gene promoters and enhancers. Further unbiased scanning of ICF1 iPSC methylomes also identifies large megabase regions of CG hypomethylation typically localized in centromeric and subtelomeric regions. RNA sequencing of ICF1 and control iPSCs reveals abnormal gene expression in ICF1 iPSCs relevant to ICF Syndrome phenotypes, some directly associated with promoter or enhancer hypomethylation. Upon differentiation of ICF1 iPSCs to mesenchymal stem cells (MSCs), we find virtually all CG hypomethylated regions remained hypomethylated when compared to either wild-type iPSC-derived MSCs or primary bone-marrow MSCs. Collectively, our results show specific methylome and transcriptome defects in both ICF1-iPSCs and differentiated somatic cell lineages, providing a valuable stem cell system for further in vitro study of the molecular pathogenesis of ICF1 Syndrome.

PMID: 25027325 [PubMed – as supplied by publisher]

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Primary immunodeficiencies underlying fungal infections.

Curr Opin Pediatr. 2013 Dec;25(6):736-47

Authors: Lanternier F, Cypowyj S, Picard C, Bustamante J, Lortholary O, Casanova JL, Puel A

Abstract
PURPOSE OF REVIEW: We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors.
RECENT FINDINGS: An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.
SUMMARY: CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.

PMID: 24240293 [PubMed – indexed for MEDLINE]

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Severe combined immunodeficiency in Brazil: management, prognosis, and BCG-associated complications.

J Investig Allergol Clin Immunol. 2014;24(3):184-91

Authors: Mazzucchelli JT, Bonfim C, Castro GG, Condino-Neto AA, Costa NM, Cunha L, Dantas EO, Dantas VM, de Moraes-Pinto MI, Fernandes JF, Goes HC, Goudouris E, Grumach AS, Guirau LM, Kuntze G, Mallozzi MC, Monteiro FP, Moraes LS, Nudelman V, Pinto JA, Rizzo MC, Porto-Neto AC, Roxo-Junior P, Ruiz M, Rullo VE, Seber A, Takano OA, Tavares FS, Toledo E, Vilela MM, Costa-Carvalho BT

Abstract
BACKGROUND: Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency. The objectives of this study were to analyze the diagnosis, treatment, and prognosis of SCID in Brazil and to document the impact of BCG vaccine.
METHODS: We actively searched for cases by contacting all Brazilian referral centers.
RESULTS: We contacted 23 centers and 70 patients from 65 families. Patients were born between 1996 and 2011, and 49 (70%) were male. More than half (39) of the diagnoses were made after 2006. Mean age at diagnosis declined from 9.7 to 6.1 months (P = .058) before and after 2000, respectively, and mean delay in diagnosis decreased from 7.9 to 4.2 months (P = .009). Most patients (60/70) were vaccinated with BCG before the diagnosis, 39 of 60 (65%) had complications related to BCG vaccine, and the complication was disseminated in 29 of 39 (74.3%). Less than half of the patients (30, 42.9%) underwent hematopoietic stem cell transplantation (HSCT). Half of the patients died (35, 50%), and 23 of these patients had not undergone HSCT. Disseminated BCG was the cause of death, either alone or in association with other causes, in 9 of 31 cases (29%, no data for 4 cases).
CONCLUSIONS: In Brazil, diagnosis of SCID has improved over the last decade, both in terms of the number of cases and age at diagnosis, although a much higher number of cases had been expected. Mortality is higher than in developed countries. Complications of BCG vaccine are an important warning sign for the presence of SCID and account for significant morbidity during disease progression.

PMID: 25011356 [PubMed – in process]

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Sarcoidosis and common variable immunodeficiency: similarities and differences.

Semin Respir Crit Care Med. 2014 Jun;35(3):330-5

Authors: Verbsky JW, Routes JM

Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency that is characterized by hypogammaglobulinemia and poor/absent specific antibody production. Granulomatous and lymphocytic interstitial lung disease (GLILD) is an increasingly recognized complication of CVID, occurring in 10 to 20% of patients. GLILD is characterized by non-necrotizing granuloma, lymphocytic interstitial pneumonitis and follicular bronchiolitis-histological patterns that are typically present in the same biopsy. GLILD is a multisystem disease and is frequently accompanied by diffuse adenopathy, splenomegaly, and extrapulmonary granulomatous disease most commonly in the lymph nodes, spleen, liver, and gastrointestinal tract. The presence of noncaseating granuloma in the lung along with some of the extrapulmonary features of GLILD may lead to an incorrect diagnosis of sarcoidosis. However, GLILD differs from sarcoidosis in several important ways including mode of presentation, extrapulmonary manifestations, radiographic abnormalities on high-resolution computed tomography scan of the chest, and laboratory features (serum immunoglobulins, bronchoalveolar lavage, and histopathology). The misdiagnosis of sarcoidosis in a patient with CVID and GLILD can lead to inappropriate treatment and increase the morbidity and mortality of the disorder.

PMID: 25007085 [PubMed – in process]

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MHC class I and II deficiencies.

J Allergy Clin Immunol. 2014 Jul 4;

Authors: Hanna S, Etzioni A

Abstract
Deficiencies of MHC complex class I or II are rare primary immunodeficiencies, both of which are inherited in an autosomal recessive pattern. MHC class II deficiency is a prototype of a disease of gene regulation. Defects in transacting regulatory factors required for expression of MHC class II genes, rather than the genes themselves, are responsible for the disease phenotype. The affected genes are known to encode 4 distinct regulatory factors controlling transcription of MHC class II genes. These transacting factors are the class II transactivator and 3 subunits of regulatory factor X (RFX): RFX containing ankyrin repeats (RFXANK), the fifth member of the RFX family (RFX5), and RFX-associated protein (RFXAP). Mutations in one of each define 4 distinct complementation groups termed A, B, C, and D, respectively. MHC class I deficiency is extremely rare and has been reported in less than 30 patients worldwide. Here we review the clinical, genetic, and molecular features that characterize these primary immunodeficiencies and discuss therapy options. Beyond the description of MHC class I and II deficiencies, their discovery has fascinated scientists and clinicians because of their ability to reveal the molecular basis of MCH regulation.

PMID: 25001848 [PubMed – as supplied by publisher]

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