Manish Butte

Fungal osteomyelitis in a patient with chronic granulomatous disease: Case report and review of the literature.

J Pak Med Assoc. 2018 Sep;68(9):1387-1390

Authors: Khalid M, Ali SA

Abstract
Chronic granulomatous disease (CGD) is the most common of the primary immunodeficiency in children. It is caused by single gene defect resulting in dysfunctional nicotinamide adenine dineucleotide phosphate (NADPH) oxidase complex causing recurrent bacterial and fungal infections. Here we present the case of a 9 year old boy who was a known case of CGD since three years of age. He presented with recent history of fever, left sided pain in the scapular region and difficulty in breathing. Chest imaging revealed developing left upper lobe consolidation and erosion of the 3rd posterior rib. The child underwent video assisted thoracoscopic surgery (VATS) and biopsy of the lesion. Histopathology revealed fungal hyphae which were confirmed to be Aspergillus nidulans on staining. He was successfully treated with voriconazole therapy. We will also review the literature on fungal osteomyelitis in CGD patients.

PMID: 30317271 [PubMed – in process]

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Eosinophilia and reduced STAT3 signalling affect neutrophil cell death in autosomal-dominant Hyper-IgE syndrome.

Eur J Immunol. 2018 Oct 13;:

Authors: Farmand S, Kremer B, Häffner M, Pütsep K, Bergman P, Sundin M, Ritterbusch H, Seidl M, Follo M, Henneke P, Henriques-Normark B

Abstract
The autosomal-dominant hyper-IgE syndrome (HIES), caused by mutations in signal transducer and activator of transcription 3 (STAT3), is a rare primary immunodeficiency which predisposes to mucocutaneous candidiasis and staphylococcal skin and lung infections. This infection phenotype is suggestive of defects in neutrophils, but data on neutrophil functions in HIES are inconsistent. This study was undertaken to functionally characterize neutrophils in STAT3-deficient HIES patients and to analyse whether the patients` eosinophilia affects the neutrophil phenotype in S. aureus infection. Neutrophil functions and cell death kinetics were studied in eight STAT3-deficient patients. Moreover, the response of STAT3-deficient neutrophils to S. aureus and the impact of autologous eosinophils on pathogen-induced cell death were analysed. No specific aberrations in neutrophil functions were detected within this cohort. However, the half-life of STAT3-deficient neutrophils ex vivo was reduced, which was partially attributable to the presence of eosinophils. Increased S. aureus-induced cell lysis, dependent on the staphylococcal virulence controlling agr-locus, was observed in STAT3-deficient neutrophils and upon addition of eosinophils. Accelerated neutrophil cell death kinetics may underlie the reported variability in neutrophil function testing in HIES. Increased S.aureus-induced lysis of STAT3-deficient neutrophils might affect pathogen control and contribute to tissue destruction during staphylococcal infections in HIES. This article is protected by copyright. All rights reserved.

PMID: 30315710 [PubMed – as supplied by publisher]

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zxcvbnUS Trends in Mortality Rates for Primary Immunodeficiency Diseases.

J Allergy Clin Immunol Pract. 2018 Oct 09;:

Authors: Fernández Pérez ER, Hunter M, Katial RK

PMID: 30312803 [PubMed – as supplied by publisher]

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Intestinal dysbiosis in Inflammatory Bowel Disease associated with primary immunodeficiency.

J Allergy Clin Immunol. 2018 Oct 09;:

Authors: Sokol H, Mahlaoui N, Aguilar C, Bach P, Join-Lambert O, Garraffo A, Seksik P, Danion F, Jegou S, Straube M, Lenoir C, Neven B, Moshous D, Blanche S, Pigneur B, Goulet O, Ruemmele F, Suarez F, Beaugerie L, Pannier S, Mazingue F, Lortholary O, Galicier L, Picard C, de Saint Basile G, Latour S, Fischer A

Abstract
The gut microbiota plays a key role in host physiology and is an actor in inflammatory bowel disease pathogenesis. Patients with primary immunodeficiency causing intestinal inflammation have disease-specific dysbiosis.

PMID: 30312711 [PubMed – as supplied by publisher]

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Correction to: Allogeneic Hematopoietic Cell Transplantation in Patients with Primary Immunodeficiencies in Korea: Eleven-Year Experience in a Single Center.

J Clin Immunol. 2018 Oct 10;:

Authors: Yi ES, Choi YB, Lee NH, Lee JW, Sung KW, Koo HH, Kang ES, Kim YJ, Yoo KH

Abstract
The original version of this article unfortunately contained a mistake in the 7th author’s given name. The correct version is presented above.

PMID: 30306363 [PubMed – as supplied by publisher]

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Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia.

Nat Commun. 2018 Oct 10;9(1):4182

Authors: McMaster ML, Berndt SI, Zhang J, Slager SL, Li SA, Vajdic CM, Smedby KE, Yan H, Birmann BM, Brown EE, Smith A, Kleinstern G, Fansler MM, Mayr C, Zhu B, Chung CC, Park JH, Burdette L, Hicks BD, Hutchinson A, Teras LR, Adami HO, Bracci PM, McKay J, Monnereau A, Link BK, Vermeulen RCH, Ansell SM, Maria A, Diver WR, Melbye M, Ojesina AI, Kraft P, Boffetta P, Clavel J, Giovannucci E, Besson CM, Canzian F, Travis RC, Vineis P, Weiderpass E, Montalvan R, Wang Z, Yeager M, Becker N, Benavente Y, Brennan P, Foretova L, Maynadie M, Nieters A, de Sanjose S, Staines A, Conde L, Riby J, Glimelius B, Hjalgrim H, Pradhan N, Feldman AL, Novak AJ, Lawrence C, Bassig BA, Lan Q, Zheng T, North KE, Tinker LF, Cozen W, Severson RK, Hofmann JN, Zhang Y, Jackson RD, Morton LM, Purdue MP, Chatterjee N, Offit K, Cerhan JR, Chanock SJ, Rothman N, Vijai J, Goldin LR, Skibola CF, Caporaso NE

Abstract
Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

PMID: 30305637 [PubMed – in process]

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[Primary immunodeficiency and inherited bone marrow failure syndrome in adults].

Rinsho Ketsueki. 2018;59(10):2204-2211

Authors: Takada H

Abstract
Primary immunodeficiency is a group of heterozygous disorders with intrinsic defects in immune cells or molecules associated with immune function. Inherited bone marrow failure syndrome is characterized by at least one defective hematopoietic cell lineage. Clinical symptoms in these patients are usually observed in childhood, but the symptoms may infrequently first occur in adulthood. Although these patients tend to develop autoimmune diseases and cancer in adulthood, recent treatment advances can ensure long-term survival. Therefore, diagnosis should not be delayed, and disease management with a view to lifelong treatment should have a long-term outlook. Therefore, we need to fully understand the pathogenesis of associated underlying complications.

PMID: 30305527 [PubMed – in process]

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[The forefront of primary immunodeficiencies].

Rinsho Ketsueki. 2018;59(10):2195-2203

Authors: Hoshino A

Abstract
Primary immunodeficiencies (PIDs) are inherited disorders caused by an impaired immune system. Because the immune system effects various immune reactions, PIDs present various clinical phenotypes including increased susceptibility to infections, autoimmunity, and malignancies. For adequate diagnosis of PIDs, a systematic approach using clinical genetic sequencing is required. New technologies including next-generation sequencing have become widely available and have led to the identification of novel genetic defects underlying PIDs. In the clinical setting, the identification of genes responsible for impaired immune system function for each PID enables the proposition of more disease-specific treatment options that target the affected signaling pathway. Research on PIDs not only benefits clinical treatment, it also provides a deeper understanding of the human immune system.

PMID: 30305526 [PubMed – in process]

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Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians’ perspectives in the endgame plan for polio eradication.

BMC Res Notes. 2018 Oct 11;11(1):717

Authors: Galal NM, Meshaal S, ElHawary R, Nasr E, Bassiouni L, Ashghar H, Farag NH, Mach O, Burns C, Iber J, Chen Q, ElMarsafy A

Abstract
OBJECTIVE: Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described.
RESULTS: Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations.

PMID: 30305145 [PubMed – in process]

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