Manish Butte

Clinical & laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma & hypogammaglobulinemia).

Clin Exp Immunol. 2018 Sep 14;:

Authors: Zaman M, Huissoon A, Buckland M, Patel S, Alachkar H, Edgar JD, Thomas M, Arumugakani G, Baxendale H, Burns S, Williams AP, Jolles S, Herriot R, Sargur RB, Arkwright PD

Abstract
Good’s syndrome (thymoma and hypogammaglobulinemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were females were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and 9 (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T-cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, SLE, Sjogren’s syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good’s syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinemia. This article is protected by copyright. All rights reserved.

PMID: 30216434 [PubMed – as supplied by publisher]

Powered by WPeMatico

Nijmegen Breakage Syndrome Complicated With Primary Pulmonary Granulomas.

Pediatrics. 2018 Sep 12;:

Authors: Marczak H, Heropolitańska-Pliszka E, Langfort R, Roik D, Grzela K

Abstract
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease characterized by microcephaly, growth retardation, severe immunodeficiency, and predisposition to lymphoid malignancy. In this report, we describe a case of a 9-year-old boy, previously diagnosed with NBS and symptoms of dyspnea, dry cough, and fever. Despite initial recognition of pneumonia, there was no response to broad spectrum antimicrobial treatment, negative results from microbiological tests, and unclear changes in lung imaging were observed. Therefore, further diagnostics were focused on suspected lymphoid malignancy and involved lung biopsy. Unexpectedly, histopathological examination revealed noncaseating granulomas. The introduction of systemic steroids resulted in significant improvement of the patient’s clinical condition. This is the first description of primary pulmonary noncaseating granulomas without nodular involvement in a child with NBS.

PMID: 30209074 [PubMed – as supplied by publisher]

Powered by WPeMatico

STAT5B deficiency due to a novel missense mutation in the coiled-coil domain.

J Allergy Clin Immunol. 2018 Sep 08;:

Authors: Acres MJ, Gothe F, Grainger A, Skelton AJ, Swan DJ, Willet JDP, Leech S, Galcheva S, Iotova V, Hambleton S, Engelhardt KR

Abstract
A novel homozygous missense mutation in the coiled-coil domain of STAT5B causes an immunodeficiency syndrome characterised by short stature due to GH insensitivity, immune dysregulation and hypothyroidism but currently without pulmonary disease or T-cell lymphopenia.

PMID: 30205186 [PubMed – as supplied by publisher]

Powered by WPeMatico

Rheumatoid nodule-like cutaneous granuloma associated with RAG1-deficient severe combined immunodeficiency: a rare case.

J Cutan Pathol. 2018 Sep 10;:

Authors: Van Horn SA, Johnson KM, Childs JM

Abstract
Noninfectious cutaneous granulomas are rare in primary immunodeficiency disorders (PID). More than three-quarters of these cases occur in combined variable immunodeficiency (CVID), ataxia telangiectasia (AT), and severe combined immunodeficiency (SCID).1 PID with both B- and T-cell deficiencies, combined with recombinase activating gene (RAG) deficiencies, are associated with epithelioid noncaseating granulomas.1-3 Cutaneous granulomas clinically present as papules, erythematous plaques, or nodules. The lesions are frequently ulcerated and scaly. The histology of cutaneous granulomas may mimic the reaction patterns found in sarcoidosis and granuloma annulare.1,4 This report presents a very rare occurrence of a rheumatoid nodule-like cutaneous granuloma in a patient with RAG1-deficient SCID. This article is protected by copyright. All rights reserved.

PMID: 30203448 [PubMed – as supplied by publisher]

Powered by WPeMatico

Epidemiology and clinical outcomes of feline immunodeficiency virus and feline leukaemia virus in client-owned cats in New Zealand.

JFMS Open Rep. 2017 Jul-Dec;3(2):2055116917729311

Authors: Luckman C, Gates MC

Abstract
Objectives: The objectives were to collect baseline data on the occurrence, testing and vaccination practices, and clinical outcomes of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in New Zealand.
Methods: A cross-sectional survey of 423 veterinary practices in New Zealand was performed to collect data on FeLV and FIV testing and vaccination during the 2015 calendar year. Clinical records from 572 cats tested using a point-of-care ELISA at a first-opinion veterinary practice between 7 April 2010 and 23 June 2016 were also obtained and multivariable logistic regression models were constructed to identify risk factors for test positivity. Survival times were estimated using Kaplan-Meier methods.
Results: The survey was completed by 112 clinics (26.4%) of which 72 performed in-house testing. Of the 2125 tests performed, 56 (2.6%) were positive for FeLV and 393 (18.5%) were positive for FIV. Fewer than 1% of cats were vaccinated for FeLV, with veterinarians citing low perceived prevalence as the primary reason for not vaccinating. Being male compared with being female and having clinical evidence of immunosuppression were significant risk factors for both FeLV and FIV test positivity. The median survival times of FeLV and FIV test-positive cats were 10 days (95% confidence interval [CI] 0-16) and 650 days (95% CI 431-993), respectively.
Conclusions and relevance: Testing and vaccination for FeLV and FIV in New Zealand appears targeted towards high-risk animals, which may bias prevalence estimates. Baseline data should be monitored for changes in FeLV epidemiology now commercial vaccines are no longer available.

PMID: 30202540 [PubMed]

Powered by WPeMatico

Interest of immunodeficiency screening in adult after admission in medical intensive care unit for severe infection, a retrospective and a prospective study: the Intensive Care Unit and Primary and Secondary Immunodeficiency (ICUSPID) study.

Infection. 2018 Sep 07;:

Authors: Baldolli A, Martin Silva N, Seguin A, Maigne G, Sultan A, Deshayes S, Du Cheyron D, Joret A, Mahlaoui N, Bienvenu B

Abstract
BACKGROUND: Primary immunodeficiency (PID) in adults is rare and mostly revealed by infections.
MATERIAL AND METHODS: Adults without predisposing factors who were admitted to an intensive care unit (ICU) for infection were screened for PID.
RESULTS: Six PID cases were diagnosed, mostly revealed by encapsulated bacterial infections.
CONCLUSION: Investigation of PID after ICU discharge should be considered to improve early detection.

PMID: 30194635 [PubMed – as supplied by publisher]

Powered by WPeMatico

The profile of IL-4, IL-5, IL-10 and GATA3 in patients with LRBA deficiency and CVID with no known monogenic disease: Association with disease severity.

Allergol Immunopathol (Madr). 2018 Sep 04;:

Authors: Azizi G, Bagheri Y, Yazdani R, Zaki-Dizaji M, Jamee M, Jadidi-Niaragh F, Kamali AN, Abolhassani H, Aghamohammadi A

Abstract
BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency (PID). LPS-responsive beige-like anchor protein (LRBA) deficiency is an autosomal recessive disease characterized by a CVID-like phenotype. T cell abnormality was reported in patients with CVID and LRBA deficiency. The study’s aim was to evaluate IL-4, IL-5, IL-10 and GATA3 expression in patients with LRBA deficiency and CVID with no known monogenic disease, and further evaluate its relevance with immunological futures and clinical complications of patients.
METHODS: The study population comprised patients with CVID, LRBA deficiency and age-sex matched healthy controls. Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. After CD4+ T cell stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, gene expression of IL-4, IL-5, IL-10 and transcription factor GATA3 was evaluated by real-time polymerase chain reaction. The protein of mentioned cytokines was assessed by enzyme-linked immunosorbent assay.
RESULTS: The main clinical presentations of CVID patients were infections only and lymphoproliferations phenotypes, but in LRBA patients were autoimmune and enteropathy phenotype. The frequencies of CD4+ T cells were significantly reduced in LRBA and CVID patients. There were no statistically significant differences among GATA3, IL4, and IL5 gene expressions by CD4+ T cells of patients and controls, however, the IL10 expressions in CVID patients was significantly lower than in LRBA patients and HCs. As compared with HCs, CVID patients showed a prominent decrease in IL-4 and IL-10 production by CD4+ T cells.
CONCLUSIONS: Our findings demonstrated that patients with CVID and LRBA deficiency (even with severe infectious and inflammatory complications) have not imbalance in Th2 response, which is in parallel with lower frequency of allergy and asthma in these patients.

PMID: 30193889 [PubMed – as supplied by publisher]

Powered by WPeMatico

The Genetic Landscape of SCID in the US and Canada in the Current Era (2010-2018).

J Allergy Clin Immunol. 2018 Sep 04;:

Authors: Dvorak CC, Haddad E, Buckley RH, Cowan MJ, Logan B, Griffith LM, Kohn DB, Pai SY, Notarangelo L, Shearer W, Prockop S, Kapoor N, Heimall J, Chaudhury S, Shyr D, Chandra S, Cuvelier G, Moore T, Shenoy S, Goldman F, Smith AR, Sunkersett G, Vander Lugt M, Caywood E, Quigg T, Torgerson T, Chandrakasan S, Craddock J, Dávila Saldaña BJ, Gillio A, Shereck E, Aquino V, DeSantes K, Knutsen A, Thakar M, Yu L, Puck JM

Abstract
In a 250 patient cohort from the US and Canada in the current era (2010-2018), we show that over 90% of patients with severe combined immunodeficiency (SCID) can be genetically-characterized.

PMID: 30193840 [PubMed – as supplied by publisher]

Powered by WPeMatico

A novel LRBA mutation presents with normal CTLA-4 and overactive Th17 immunity.

J Allergy Clin Immunol. 2018 Sep 04;:

Authors: De Bruyne M, Bogaert DJ, Venken K, Van den Bossche L, Bonroy C, Roels L, Tavernier SJ, van de Vijver E, Driessen A, van Gijn M, Gámez-Diaz L, Elewaut D, Grimbacher B, Haerynck F, Moes N, Dullaers M

Abstract
We report normal CTLA-4 expression and Treg cell function in the face of overactive Th17 immunity in an LRBA-deficient patient, illustrating that CTLA-4 absence is not a prerequisite for development of autoimmunity in this disorder.

PMID: 30193839 [PubMed – as supplied by publisher]

Powered by WPeMatico

Structural Basis for Regulation of Phosphoinositide Kinases and Their Involvement in Human Disease.

Mol Cell. 2018 Sep 06;71(5):653-673

Authors: Burke JE

Abstract
Lipid phosphoinositides play fundamental roles in virtually all pathways that control a cell’s decision to grow, move, divide, and die. Because of this, kinases that phosphorylate phosphoinositide lipids are critically involved in myriad essential functions including growth, development, and membrane trafficking. The misregulation of phosphoinositide kinases is critical in human diseases, including cancer, primary immunodeficiencies, and developmental disorders. Phosphoinositide kinases also play a role in mediating bacterial and viral infections for many potent human pathogens. Furthermore, inhibitors of parasite phosphoinositide kinases are in development as therapies for both malaria and cryptosporidiosis. Therefore, understanding how phosphoinositide kinases are regulated has implications for the treatment of many devastating human diseases. Recent structures of phosphoinositide kinases have revealed unique molecular insight into their regulation. This review will summarize our current molecular knowledge on phosphoinositide kinase regulation, and how this information is being used to generate novel small molecule inhibitors as potential therapeutics.

PMID: 30193094 [PubMed – in process]

Powered by WPeMatico