Manish Butte

Hypomorphic DOCK8 deletion causes hypereosinophilic syndrome.

Pediatr Blood Cancer. 2019 Nov 20;:e28084

Authors: Aryan Z, Nabavi M, Shabani M, Keles S, Zoghi S, Chatila T, Rezaei N

PMID: 31749288 [PubMed – as supplied by publisher]

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BCG Moreau Vaccine Safety Profile and NK Cells-Double Protection Against Disseminated BCG Infection in Retrospective Study of BCG Vaccination in 52 Polish Children with Severe Combined Immunodeficiency.

J Clin Immunol. 2019 Nov 20;:

Authors: Bernatowska E, Skomska-Pawliszak M, Wolska-Kuśnierz B, Pac M, Heropolitanska-Pliszka E, Pietrucha B, Bernat-Sitarz K, Dąbrowska-Leonik N, Bohynikova N, Piątosa B, Lutyńska A, Augustynowicz E, Augustynowicz-Kopeć E, Korzeniewska-Koseła M, Krasińska M, Krzysztopa-Grzybowska K, Wieteska-Klimczak A, Książyk J, Jackowska T, van den Burg M, van Dongen JJM, Casanova JL, Picard C, Mikołuć B

Abstract
OBJECTIVES: The aim of the study was to estimate the rate of adverse reactions to live BCG Moreau vaccine, manufactured by Biomed in Poland, in severe combined immunodeficiency (SCID) patients.
MATERIAL: The profiles of 52 SCID patients vaccinated at birth with BCG, hospitalized in Children’s Memorial Health Institute, Warsaw (CMHI), in the years 1980-2015 were compared with those of 349 BCG-vaccinated SCID patients from other countries analyzed by Beatriz E. Marciano et al. in a retrospective study (Marciano et al. J Allergy Clin Immunol. 2014;133(4):1134-1141).
RESULTS: Significantly less disseminated BCG infections (10 out of 52 SCID, 19%) occurred in comparison with Marciano study-119 out of 349, 34% (p = 0.0028), with no death in patients treated with SCID anti-TB drug, except one in lethal condition. In our study, disseminated BCG infection was observed only in SCID with TB+NK- phenotype and significantly lower NK cell counts (p = 0.0161). NK cells do not influence on the frequency of local BCG reaction. A significantly higher number of hematopoietic stem cells transplantations (HSCT) were performed in CMHI study (p = 0.0001). Anti-TB treatment with at least two medicines was provided.
CONCLUSION: The BCG Moreau vaccine produced in Poland, with well-documented genetic characteristics, seems to be safer than other BCG substrains used in other regions of the world. Importantly, NK cells seem to play a role in protecting SCID patients against disseminated BCG complications, which NK- SCID patients are more prone to. HSCT and TB therapy could be relevant due to the patients’ survival and the fact that they protect against BCG infection.

PMID: 31749033 [PubMed – as supplied by publisher]

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mRNA and piRNA profile in chemical-induced oral squamous cell carcinoma mice model.

Exp Anim. 2019 Nov 19;:

Authors: Wu L, Jiang Y, Zheng Z, Li H, Cai M, Pathak JL, Li Z, Huang L, Zeng M, Zheng H, Ouyang K, Gao J

Abstract
Piwi-interacting RNAs (piRNAs), a novel class of noncoding RNAs, are involved in the carcinogenesis. However, the functional significance of piRNAs in oral squamous cell carcinoma (OSCC) remains unknown. In the present study, we used chemical carcinogen 4NQO to induced OSCC mouse model. piRNAs and mRNAs were profiled using next-generation sequencing in the tongue tumor tissues from 4NQO induction and healthy tongue tissues from control mice. Furthermore, we analyzed the differential gene expression of human OSCC in GEO database. According to the common differentially expressed genes in the 4NQO model and human OSCC tissues, piRNAs and mRNAs network were established based on informatics method. A total of 14 known piRNAs and 435 novel predicted piRNAs were differently expressed in tumor tissue compared to healthy tissue. Among differently expressed piRNAs 260 were downregulated, and 189 were upregulated. The mRNA targets for the differentially expressed piRNAs were identified using RNAhybrid software. Primary immunodeficiency and herpes simplex infection were the most enriched pathways. A total of 22 mRNAs overlapped in human and mice OSCC. Moreover, we established the regulatory network of 11 mRNAs, including Tmc5, Galnt6, Spedf, Mybl2, Muc5b, Six31, Pigr, Lamc2, Mmp13, Mal, and Mamdc2, and 11 novel piRNAs. Our data showed the interaction between piRNAs and mRNAs in OSCC, which might provide new insights in the development of diagnostic biomarkers and therapeutic targets of OSCC.

PMID: 31748426 [PubMed – as supplied by publisher]

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Author Correction: A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.

Nat Commun. 2019 Nov 20;10(1):5337

Authors: Tavernier SJ, Athanasopoulos V, Verloo P, Behrens G, Staal J, Bogaert DJ, Naesens L, De Bruyne M, Van Gassen S, Parthoens E, Ellyard J, Cappello J, Morris LX, Van Gorp H, Van Isterdael G, Saeys Y, Lamkanfi M, Schelstraete P, Dehoorne J, Bordon V, Van Coster R, Lambrecht BN, Menten B, Beyaert R, Vinuesa CG, Heissmeyer V, Dullaers M, Haerynck F

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 31745085 [PubMed – in process]

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A Rare Case of Vocal Cord Aspergillosis.

Indian J Otolaryngol Head Neck Surg. 2019 Oct;71(Suppl 1):868-871

Authors: Chouksey S, Thulasidas P

Abstract
Primary aspergillosis of larynx is very rare. Till now only 28 cases of isolated laryngeal aspergillosis are documented in the English literature. In the field of otorhinolaryngology, aspergillosis most frequently affects external auditory canal or nasal sinuses and larynx is usually secondarily involved. It usually affects the patients with immunocompromised state and usually presents with hoarseness of voice. Laryngeal lesions usually mimics malignancy, so accurate diagnosis with direct laryngoscopy and biopsy is needed for further management. As these lesions responds very well to antifungal therapy, early diagnosis and starting antifungal therapy is important. Here we are presenting a case report of 67 years old male with aspergillosis of vocal folds without any immunodeficiency.

PMID: 31742084 [PubMed]

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Novel nonsense IL-12Rβ1 mutation associated with recurrent tuberculosis.

Immunol Res. 2019 Nov 18;:

Authors: Ul Akbar N, Khan SN, Amin MU, Ishfaq M, Cabral-Marques O, Schimke LF, Iqbal A, Ullah I, Hussain M, Ali I, Khan N, El Khawanky N, Rahman H, Khan TA

Abstract
The interleukin (IL)-12/interferon(IFN)γ axis plays an important role in the control of mycobacterial diseases as demonstrated by the increased susceptibility to mycobacterial species in patients with an inborn error of the IL-12-dependent IFNγ immunity. Here, we report a novel mutation in the IL-12Rβ1 gene in a female Pakistani patient who was born in a consanguineous marriage and developed severe bacille Calmette-Guérin (BCG) infection and recurrent tuberculosis. After reviewing the patient’s clinical records, she was investigated for IL-12/IFNγ defects using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and DNA genetic Sanger sequencing. Quantification of secretory cytokines from the patient’s peripheral blood mononuclear cells (PBMCs) revealed significantly reduced IFNγ production. Flow cytometric analysis revealed no surface expression of IL-12Rβ1 on PHA-activated T lymphocytes. In addition, IL-12-induced impaired STAT4 phosphorylation in the patient’s lymphocytes when compared with those from five healthy controls. The genetic analysis of IL-12Rβ1 gene identified a novel nonsense mutation c.199G>T/p.E67* within exon 3, which encodes part of the cytokine-binding region (CBR). In silico analysis indicates that this novel nonsense mutation generates a truncated protein with an apparent inactivating effect. Our data expand the genetic spectrum of IL-12Rβ1 deficiency. Moreover, our findings highlight the need for developing newborn screening for patients with primary immunodeficiency associated with mycobacterial infections in areas where BCG vaccination is mandatory in order to improve the treatment of patients, and consequently their quality of life.

PMID: 31741236 [PubMed – as supplied by publisher]

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Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency.

Curr Allergy Asthma Rep. 2019 Nov 18;19(11):52

Authors: Lum SH, Hoenig M, Gennery AR, Slatter MA

Abstract
PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID.
RECENT FINDINGS: Conventional myeloablative conditioning regimens are associated with significant acute toxicities, transplant-related mortality, and late effects such as infertility. Reduced toxicity conditioning regimens have had significant positive impacts on HCT outcome, and there are now well-established strategies in children with PID. Treosulfan has emerged as a promising preparative agent. Use of a peripheral stem cell source has been shown to be associated with better donor chimerism in patients receiving reduced toxicity conditioning. Minimal conditioning regimens using monoclonal antibodies are in clinical trials with promising results thus far. Reduced toxicity conditioning has emerged as standard of care for PID and has resulted in improved transplant survival for patients with significant comorbidities.

PMID: 31741098 [PubMed – in process]

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Acute primary purulent pericarditis in an adult patient with unknown X-linked agammaglobulinemia.

Immunobiology. 2019 Nov 04;:

Authors: Martignani C, Massaro G, Bruno AG, Biffi M, Ziacchi M, Diemberger I

Abstract
X-linked agammaglobulinemia (XLA) is a rare form of inherited immunodeficiency due to an impairment in B-lymphocyte differentiation and maturation. In the majority of cases XLA is diagnosed in childhood, particularly among males affected by recurrent infections and with a family history of immunodeficiency. Infections of respiratory tract, gastrointestinal apparatus, eyes, nose and ears are frequent in XLA patients; on the contrary, infections of myocardium, cardiac valves and pericardium are rarely described in XLA. A 34-year-old man with unknown XLA was hospitalized because of syncope, due to pericardial tamponade, caused by acute primary purulent pericarditis. Immediate pericardiocentesis was effective in improving hemodynamics, and empiric antibiotic therapy was successful in controlling the infection. Purulent pericarditis is a rare disease with high mortality rate: it is usually caused by hematogenous bacterial propagation, direct infection of pericardial space by chest wounds or thoracic surgery, or extension of infection from adjacent tissues. However, this patient had no recent local or systemic infections. Because of unusual clinical picture during hospitalization he underwent further clinical and laboratory evaluations, that showed low immunoglobulin levels. After exclusion of acquired immunodeficiency, genetic tests were performed: they detected deletion of exons 8-9-10 of Bruton Tyrosine Kinase gene on X chromosome, leading to the diagnosis of XLA. Acute purulent primary pericarditis may also occur in adult XLA patients as first clinical manifestation. According to this case report, a primary immunodeficiency syndrome should be considered in patients with atypical cardiac infections and no predisposing conditions, regardless of age.

PMID: 31740078 [PubMed – as supplied by publisher]

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A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress.

Dis Model Mech. 2019 Nov 14;:

Authors: Rissone A, Jimenez E, Bishop K, Carrington B, Slevin C, Wincovitch SM, Sood R, Candotti F, Burgess SM

Abstract
Mutations in the gene AK2 are responsible for Reticular Dysgenesis (RD), a rare and severe form of primary immunodeficiency in children. RD patients have a severely shortened life expectancy and without treatment die, generally from sepsis early after birth. The only available therapeutic option for RD is hematopoietic stem cell transplantation (HSCT). To gain insight into the pathophysiology of RD, we previously created zebrafish models for AK2 deficiencies. One of the clinical features of RD is hearing loss, but its pathophysiology and causes have not been determined. In adult mammals, sensory hair cells of the inner ear do not regenerate; however, their regeneration has been observed in several non-mammalian vertebrates, including zebrafish. Therefore, we used our RD zebrafish models to determine if AK2 deficiency affects sensory organ development and/or hair cell regeneration. Our studies indicated that AK2 is required for the correct development, survival and regeneration of sensory hair cells. Interestingly, AK2 deficiency induces the expression of several oxidative stress markers and it triggers an increased level of cell death in the hair cells. Finally, we show that glutathione treatment can partially rescue hair cell development in the sensory organs in our RD models, pointing to the potential use of antioxidants as a therapeutic treatment supplementing HSCT to prevent or ameliorate sensorineural hearing deficits in RD patients.

PMID: 31727854 [PubMed – as supplied by publisher]

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Universal donor strategy for primary immunodeficiency.

Blood. 2019 Nov 14;134(20):1688-1689

Authors: Gennery AR

PMID: 31725867 [PubMed – in process]

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