Manish Butte

BAFF and BAFF-Receptor in B Cell Selection and Survival.

Front Immunol. 2018;9:2285

Authors: Smulski CR, Eibel H

Abstract
The BAFF-receptor (BAFFR) is encoded by the TNFRSF13C gene and is one of the main pro-survival receptors in B cells. Its function is impressively documented in humans by a homozygous deletion within exon 2, which leads to an almost complete block of B cell development at the stage of immature/transitional B cells. The resulting immunodeficiency is characterized by B-lymphopenia, agammaglobulinemia, and impaired humoral immune responses. However, different from mutations affecting pathway components coupled to B cell antigen receptor (BCR) signaling, BAFFR-deficient B cells can still develop into IgA-secreting plasma cells. Therefore, BAFFR deficiency in humans is characterized by very few circulating B cells, very low IgM and IgG serum concentrations but normal or high IgA levels.

PMID: 30349534 [PubMed – in process]

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Immunosuppression for immunodeficiency- getting smarter.

J Allergy Clin Immunol. 2018 Oct 16;:

Authors: Lucy D, Eyal G

PMID: 30339850 [PubMed – as supplied by publisher]

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Asthma: Differential Diagnosis and Comorbidities.

Front Pediatr. 2018;6:276

Authors: Ullmann N, Mirra V, Di Marco A, Pavone M, Porcaro F, Negro V, Onofri A, Cutrera R

Abstract
Childhood asthma remains a multifactorial disease with heterogeneous clinical phenotype and complex genetic inheritance. The primary aim of asthma management is to achieve control of symptoms, in order to reduce the risk of future exacerbations and progressive loss of lung function, which results especially challenging in patients with difficult asthma. When asthma does not respond to maintenance treatment, firstly, the correct diagnosis needs to be confirmed and other diagnosis, such as cystic fibrosis, primary ciliary dyskinesia, immunodeficiency conditions or airway and vascular malformations need to be excluded. If control remains poor after diagnostic confirmation, detailed assessments of the reasons for asthma being difficult-to-control are needed. Moreover, all possible risk factors or comorbidities (gastroesophageal reflux, rhinosinusitis, dysfunctional breathing and/or vocal cord dysfunction, obstructive sleep apnea and obesity) should be investigated. At the same time, the possible reasons for poor symptom control need to be find in all modifiable factors which need to be carefully assessed. Non-adherence to medication or inadequate inhalation technique, persistent environmental exposures and psychosocial factors are, currently, recognized as the more common modifiable factors. Based on these premises, investigation and management of asthma require specialist multidisciplinary expertise and a systematic approach to characterizing patients’ asthma phenotypes and delivering individualized care. Moreover, since early wheezers are at higher risk of developing asthma, we speculate that precocious interventions aimed at early diagnosis and prevention of modifiable factors might affect the age at onset of wheezing, reduce the prevalence of persistent later asthma and determine long term benefits for lung health.

PMID: 30338252 [PubMed]

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Discovering aspects of health-experiences of a web-based health diary among adults with primary immunodeficiency.

Nurs Open. 2018 Oct;5(4):642-648

Authors: Petersson C, Björkander J, Fust R

Abstract
Aim: Advances in technology generate new opportunities to develop e-health tools to help individuals in self-management by assessing symptoms of illness and its relation to treatments. Self-management is central when living with primary immunodeficiency diseases. The aim was to explore the experiences of people living with primary immunodeficiency, who used a pilot version of the web-based health diary.
Design: Explorative design.
Methods: In total, 16 participants (median age 59) attended one of three focus groups. Inductive content analysis was used.
Results: The participants could be encouraged to discover aspects of their health by contributing to documentation which could support the health concept. A greater understanding about their own health and communicating with healthcare professionals during encounters was expressed. The web-based health diary is a helpful tool to discover aspects of health that affects the individuals’ life situation and assists the self-management of a long-term condition such as immunodeficiency.

PMID: 30338110 [PubMed]

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Gastroduodenal Disorders in Patients with CVID Undergoing Immuno-globulin Therapy.

Curr Pharm Biotechnol. 2018 Oct 10;:

Authors: Varricchi G, Pecoraro A, Crescenzi L, Marone G, Travaglino A, D’Armiento FP, Genovese A, Spadaro G

Abstract
BACKGROUND: Common variable immunodeficiency (CVID) encompasses a heterogeneous group of primary antibody deficiency disorders characterized by recurrent infections, autoimmunity and malignancies. Gastrointestinal manifestations are frequently associated with CVID.
OBJECTIVE: In this cross-sectional study, we evaluated gastric and duodenal involvement in a cohort of adult patients with CVID.
METHODS: Upper gastrointestinal endoscopy was performed in 58 patients (26 males, mean age 47.8±15.6 years), diagnosed with CVID according to 2014 ESID criteria. Random biopsies were col-lected from gastric antrum and descending duodenum for the all enrolled subjects. Intraepithelial lympho-cytosis in descending duodenum was defined as the presence of 25 lymphocytes per 100 enterocytes.
RESULTS: The major histopathological findings that we found were: a) chronic active gastritis (44.8%), Helicobacter pylori-associated (8.6%), b) chronic duodenitis (39.6%) with intraepithelial lymphocytosis (31%) and absence of plasma cells (18.9%) and c) autoimmune atrophic gastritis (5.2%). Three patients (5.2%) presented Intestinal Metaplasia (IM) of the gastric antrum. This finding was associated with H. pylori infection and persisted after the eradication in one patient. IM was associated with autoimmune atrophic gastritis in two cases. Giardia lamblia infection was observed in the duodenum samples from three patients (5.2%). A diagnosis of Gastric adenocarcinoma was made in a 58-year- old woman diag-nosed with gastric dysplasia one year earlier.
CONCLUSION: In our cohort of CVID patients, gastro-duodenal histopathological findings, including ma-lignancies, are frequent and can affect long-term prognosis. A rigorous endoscopic follow-up is needed in CVID patients irrespective of the gastrointestinal symptoms.

PMID: 30336770 [PubMed – as supplied by publisher]

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Human primary immunodeficiency caused by expression of a kinase-dead p110δ mutant.

J Allergy Clin Immunol. 2018 Oct 15;:

Authors: Cohen SB, Bainter W, Johnson JL, Lin TY, Wong JCY, Wallace J, Jones J, Mir F, Qamar F, Cantley LC, Geha RS, Chou J

Abstract
This case demonstrates the essential contribution of the p110δ catalytic domain in adaptive immunity function in a patient with expression of a kinase-dead p110δ mutant.

PMID: 30336224 [PubMed – as supplied by publisher]

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Activated Phosphoinositide 3 Kinase Delta Syndrome (APDS): A Primary Immunodeficiency Mimicking Lymphoma.

J Pediatr Hematol Oncol. 2018 Oct 16;:

Authors: Baleydier F, Ranza E, Schäppi M, Rougemont AL, Merlini L, Ansari M, Blanchard-Rohner G

Abstract
Malignant or nonmalignant lymphoproliferative disorders together with repeated ear, nose, and throat infections should strongly motivate immunologic investigations. Indeed, we report a 7-year-old patient with a history of persistent abdominal symptoms along with recurrent ear, nose, and throat infections, who presented with intra-abdominal masses highly suggestive of a diagnostic of lymphoma, and who was diagnosed with activated-PI3K-delta syndrome, a recently described primary immunodeficiency prone to lymphoproliferation.

PMID: 30334905 [PubMed – as supplied by publisher]

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Embryonic Stem Cell Models of Human Brain Tumors.

Methods Mol Biol. 2019;1869:127-142

Authors: Morrison LC, Tatari N, Werbowetski-Ogilvie TE

Abstract
Utilization of human embryonic stem cells (hESCs) as a model system to study highly malignant pediatric cancers has led to significant insight into the molecular mechanisms governing tumor progression and has revealed novel therapeutic targets for these devastating diseases. Here, we describe a method for generating heterogeneous populations of neural precursors from both normal and neoplastic hESCs and the subsequent injection of neoplastic human embryonic neural cells (hENs) into intracerebellar or intracranial xenograft models. Histopathologically, neural tumors derived from neoplastic hENs exhibit features similar to more aggressive medulloblastoma, the most common malignant primary pediatric brain tumor. In this chapter, we will outline the detailed methods for culturing normal and neoplastic neural precursor cells in both adherent and tumorsphere format and the full characterization of the brain tumors generated from these cells in non-obese diabetic severe combined immunodeficiency (NOD SCID) mice.

PMID: 30324520 [PubMed – in process]

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Corrigendum: Interleukin-2-Inducible T-Cell Kinase Deficiency-New Patients, New Insight?

Front Immunol. 2018;9:2197

Authors: Ghosh S, Drexler I, Bhatia S, Adler H, Gennery AR, Borkhardt A

Abstract
[This corrects the article DOI: 10.3389/fimmu.2018.00979.].

PMID: 30323808 [PubMed – in process]

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Management of Urethritis: Is It Still the Time for Empirical Antibiotic Treatments?

Eur Urol Focus. 2018 Oct 11;:

Authors: Bartoletti R, Wagenlehner FME, Bjerklund Johansen TE, Köves B, Cai T, Tandogdu Z, Bonkat G

Abstract
CONTEXT: Urethritis prevalence in Europe changed in the last years due to both the increase of migratory streams from North Africa and the more frequent exposition of males to relevant risk factors. Owing to these reasons, urethritis treatment should be optimized by accurate microbiological investigations to avoid the risk of persistence, recurrence, or reinfection.
OBJECTIVE: The aim of this systematic review is to optimize the treatments for urethritis and investigate the applicability of nucleic acid amplification test (NAAT) as the primary microbiological investigation.
EVIDENCE ACQUISITION: A literature search in Medline, Cochrane, and Google Scholar databases was conducted up to June 2018. Subject headings were selected as follows: Urethritis OR gonococcal urethritis OR non-gonococcal urethritis AND Antibiotics OR Recurrence. A total of 528 abstracts were identified and selected. Finally, 12 full-text articles were selected for a qualitative synthesis. The Preferred Reported Items for Systematic Reviews and Meta-Analyses statement was used to perform an accurate research checklist and report.
EVIDENCE SYNTHESIS: Empirical treatments are no more recommended, although a broad spectrum of antibiotic therapy may be initiated while awaiting the results from pathogens’ microbiological characterization. First-line treatment for gonococcal urethritis consists of a single dose of ceftriaxone/azithromycin combined therapy. Specific therapies should be initiated for nongonococcal urethritis according to each single pathogen involved in the infection process. Owing to this reason, NAAT is mandatory in the clinical approach to the disease, although the Gram stain of urethral discharge or smear remains applicable for some less frequent nongonococcal urethritis. Moreover, the urethritis “modern view” also includes noninfectious etiologies that occurred after traumas or injection of irritating compounds. Sexual abstinence of at least 7 d should be observed from the start of treatment to avoid reinfection, while sexual partners should evenly be treated.
CONCLUSIONS: The treatment of urethritis implies accurate determination of pathogens involved in the infection process by NAAT with subsequent appropriate antibiotic therapy, thus avoiding the risk of antibiotic resistance and overuse of antibiotics indicated for empirical treatments. The population exposed to relevant risk factors should be adequately informed about the increased risk of developing infections and motivated toward the intensive use of condoms during sexual intercourses.
PATIENT SUMMARY: Urethritis is a sexually transmitted disease generally characterized by urethral discharge or other symptoms such as itching, tingling, and apparent difficulties in having a regular urinary flow. Microbiological investigations are mandatory to obtain satisfactory results from the treatment. Multiple antibiotic treatments are often necessary due to the high risk of multiple pathogens responsible for the disease. Similarly, sexual partners should be investigated and treated in the same way. Several risk factors such as immunodeficiency, multiple sexual partners, homo- and bisexuality, and alcohol abuse may be related to the disease. In these cases, the use of condom is strongly recommended.

PMID: 30318465 [PubMed – as supplied by publisher]

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