Manish Butte

Direct examination of Gram negative spiral-shaped rods: what is hidden behind the Campylobacter spp. ?

Clin Microbiol Infect. 2020 Jul 30;:

Authors: Boyer PH, Talagrand-Reboul É, Guffroy A, Schramm F, Jaulhac B, Grillon A

PMID: 32739339 [PubMed – as supplied by publisher]

Powered by WPeMatico

Fungal infections in primary immunodeficiency diseases.

Clin Immunol. 2020 Jul 29;:108553

Authors: Elaziz DA, El-Ghany MA, Meshaal S, El Hawary R, Lotfy S, Galal N, Ouf SA, Elmarsafy A

Abstract
Primary immunodeficiency diseases (PID), encompass a heterogeneous group of diseases, with increased susceptibility to recurrent, severe infections. Invasive fungal infections raise a serious concern related to their morbidity and mortality. Herein, we describe various fungal infections among different PID patients. Twenty-eight PID patients diagnosed with fungal infections were included; fourteen patients with chronic granulomatous disease, two with Hyper Immunoglobulin E syndrome, one with LRBA deficiency and one with MHC class II defect, one with unclassified immune dysregulation, one with CD4 lymphopenia and one patient with Immune dysregulation Polyendocrinopathy Enteropathy X-linked syndrome. Aspergillus species were the most common isolated causative organisms in 78% of patients, Candida species were the causative organisms in 32%, Pneumocystis jirovecii caused infections in 7% followed by Malassezia furfur, Fusarium spp., Mucormycosis, and Penicillium chrysogenium 3.5% for each. The mortality rate among our patients was 10/28 (35.7%). PID patients are at high risk of developing fungal infections.

PMID: 32738296 [PubMed – as supplied by publisher]

Powered by WPeMatico

Common variable immunodeficiency with granulomatous-lymphocytic interstitial lung disease and preceding neurological involvement: a case-report.

BMC Pulm Med. 2020 Jul 31;20(1):205

Authors: Cowen JE, Stevenson J, Paravasthu M, Darroch J, Jacob A, Tueger S, Gosney JR, Simons A, Spencer LG, Judge EP

Abstract
BACKGROUND: Common variable immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies characterised by a dysregulated and impaired immune response. In addition to an increased susceptibility to infection, it is also associated with noninfectious autoimmune and lymphoproliferative complications. CVID is rarely associated with neurological complications. Pulmonary involvement is more common, and patients can develop an interstitial lung disease known as granulomatous-lymphocytic interstitial lung disease (GLILD).
CASE PRESENTATION: A 50-year-old Caucasian female with a history of Evans syndrome (idiopathic thrombocytopaenic purpura and autoimmune haemolytic anaemia) and hypogammaglobulinaemia initially presented to the neurology clinic with marked cerebellar ataxia and headaches. Following extensive investigation (which included brain biopsy), she was diagnosed with neuro-sarcoidosis and her symptoms resolved following treatment with immunosuppressive therapy. Over the following 10 years, she was extensively investigated for recurrent pulmonary infections and abnormal radiological findings, which included pulmonary nodules, infiltrates and splenomegaly. Subsequently, she was referred to an immunology clinic, where immunoglobulin replacement treatment was started for what was ultimately considered to be CVID. Shortly afterwards, evaluation of her clinical, radiological and histological findings at a specialist interstitial lung disease clinic led to a diagnosis of GLILD.
CONCLUSION: CVID is a condition which should be suspected in patients with immunodeficiency and recurrent infections. Concomitant autoimmune disorders such as haemolytic anaemia and immune thrombocytopenia may further support the diagnosis. As illustrated in this case, there is a rare association between CVID and inflammatory involvement of the neurological system. Respiratory physicians should also suspect CVID with associated GLILD in patients with apparent pulmonary granulomatous disease and recurrent infections. In addition, this case also highlights the challenge of diagnosing CVID and its associated features, and how the definitive exclusion of other pathologies such as malignancy, mycobacterial infection and lymphoma is required as part of this diagnostic process.

PMID: 32736614 [PubMed – as supplied by publisher]

Powered by WPeMatico

Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans.

Immunity. 2020 Jul 24;:

Authors: Cytlak U, Resteu A, Pagan S, Green K, Milne P, Maisuria S, McDonald D, Hulme G, Filby A, Carpenter B, Queen R, Hambleton S, Hague R, Lango Allen H, Thaventhiran JED, Doody G, Collin M, Bigley V

Abstract
The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXL+SIGLEC6+ pre-DC, DC2 and DC3. The origin of this heterogeneity is unknown. Using high-dimensional analysis, in vitro differentiation, and an allelic series of human IRF8 deficiency, we demonstrated that cDC2 (CD1c+DC) heterogeneity originates from two distinct pathways of development. The lymphoid-primed IRF8hi pathway, marked by CD123 and BTLA, carried pDC, cDC1, and DC2 trajectories, while the common myeloid IRF8lo pathway, expressing SIRPA, formed DC3s and monocytes. We traced distinct trajectories through the granulocyte-macrophage progenitor (GMP) compartment showing that AXL+SIGLEC6+ pre-DCs mapped exclusively to the DC2 pathway. In keeping with their lower requirement for IRF8, DC3s expand to replace DC2s in human partial IRF8 deficiency.

PMID: 32735845 [PubMed – as supplied by publisher]

Powered by WPeMatico

National external quality assessment for next-generation sequencing-based diagnostics of primary immunodeficiencies.

Eur J Hum Genet. 2020 Jul 30;:

Authors: Elsink K, Huibers MMH, Hollink IHIM, van der Veken LT, Ernst RF, Simons A, Zonneveld-Huijssoon E, van der Hout AH, Abbott KM, Hoischen A, Pieterse M, Kuijpers TW, van Montfrans JM, van Gijn ME

Abstract
Dutch genome diagnostic centers (GDC) use next-generation sequencing (NGS)-based diagnostic applications for the diagnosis of primary immunodeficiencies (PIDs). The interpretation of genetic variants in many PIDs is complicated because of the phenotypic and genetic heterogeneity. To analyze uniformity of variant filtering, interpretation, and reporting in NGS-based diagnostics for PID, an external quality assessment was performed. Four main Dutch GDCs participated in the quality assessment. Unannotated variant call format (VCF) files of two PID patient analyses per laboratory were distributed among the four GDCs, analyzed, and interpreted (eight analyses in total). Variants that would be reported to the clinician and/or advised for further investigation were compared between the centers. A survey measuring the experiences of clinical laboratory geneticists was part of the study. Analysis of samples with confirmed diagnoses showed that all centers reported at least the variants classified as likely pathogenic (LP) or pathogenic (P) variants in all samples, except for variants in two genes (PSTPIP1 and BTK). The absence of clinical information complicated correct classification of variants. In this external quality assessment, the final interpretation and conclusions of the genetic analyses were uniform among the four participating genetic centers. Clinical and immunological data provided by a medical specialist are required to be able to draw proper conclusions from genetic data.

PMID: 32733070 [PubMed – as supplied by publisher]

Powered by WPeMatico

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers.

Biomolecules. 2020 Jul 28;10(8):

Authors: Baleydier F, Bernard F, Ansari M

Abstract
Many primary immunodeficiencies (PIDs) are recognised as being associated with malignancies, particularly lymphoid malignancies, which represent the highest proportion of cancers occurring in conjunction with this underlying condition. When patients present with genetic errors of immunity, clinicians must often reflect on whether to manage antitumoral treatment conventionally or to take a more personalised approach, considering possible existing comorbidities and the underlying status of immunodeficiency. Recent advances in antitumoral immunotherapies, such as monoclonal antibodies, antigen-specific adoptive cell therapies or compounds with targeted effects, potentially offer significant opportunities for optimising treatment for those patients, especially with lymphoid malignancies. In cases involving PIDs, variable oncogenic mechanisms exist, and opportunities for antitumoral immunotherapies can be considered accordingly. In cases involving a DNA repair defect or genetic instability, monoclonal antibodies can be proposed instead of chemotherapy to avoid severe toxicity. Malignancies secondary to uncontrolled virus-driven proliferation or the loss of antitumoral immunosurveillance may benefit from antivirus cell therapies or allogeneic stem cell transplantation in order to restore the immune antitumoral caretaker function. A subset of PIDs is caused by gene defects affecting targetable signalling pathways directly involved in the oncogenic process, such as the constitutive activation of phosphoinositol 3-kinase/protein kinase B (PI3K/AKT) in activated phosphoinositide 3-kinase delta syndrome (APDS), which can be settled with PI3K/AKT inhibitors. Therefore, immunotherapy provides clinicians with interesting antitumoral therapeutic weapons to treat malignancies when there is an underlying PID.

PMID: 32731356 [PubMed – in process]

Powered by WPeMatico

Disparities in Outcomes of CD8+ Cutaneous T Cell Lymphoma by Race and Presenting Lesion Location.

Br J Dermatol. 2020 Jul 30;:

Authors: Mirza FN, Yumeen S, Girardi M

Abstract
While cutaneous T-cell lymphoma (CTCL) presents most commonly with a CD4+ phenotype, CD8+ and CD30+ variants have also been described. CD8+ variants include primary cutaneous epidermotropic cytotoxic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous CD8+ lymphomas associated with immunodeficiency, and CD8+ variants of other well-defined CTCLs1 . While the epidemiology of other CTCLs has been well described, there remains a dearth of literature characterizing the incidence and survival patterns of CD8+ CTCL2 . Thus, we aimed to better characterize data on US national epidemiologic trends of this diverse group of malignancies using the Surveillance, Epidemiology, and End Results (SEER) database.

PMID: 32730673 [PubMed – as supplied by publisher]

Powered by WPeMatico