ResearchPad - Immunology and Allergy https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Fertility Treatment Resulting in Live Births in Women with Asthma – Associated with Perennial Allergy?]]> https://www.researchpad.co/product?articleinfo=N826dae41-c3e1-4b66-9472-a37312134eb7

Background

Asthma has been linked with prolonged time to pregnancy compared to healthy controls, also asthma has been linked to a higher need for fertility treatment. However, knowledge of the possible association between allergy and need for fertility treatment is limited. Our aim was to explore a possible difference in having had fertility treatment in women with asthma and live births in those with perennial allergy (animals, fungi and dust mites) compared to no allergy/seasonal allergy. The primary outcome of interest was fertility treatment.

Patients and Methods

Women enrolled in the Management of Asthma during Pregnancy (MAP) program at Hvidovre Hospital, DK, were included in the present analysis provided they fulfilled the following criteria: 1) diagnosed with asthma and current anti-asthma therapy and 2) first visit to the respiratory outpatient clinic within the first 18 weeks of pregnancy. Participants were divided into two groups: asthma with perennial allergy (cases) and asthma with seasonal/no allergy (controls). Logistic regression analysis was applied, and findings expressed as odds ratios (OR).

Results

Among women with asthma and perennial allergy (n=544 cases), 13.8% (n=75) had fertility treatment, compared to only 10.1% (n=39) among women with asthma and seasonal/no allergy (n=388, controls) (OR 1.43, 95% CI 0.95–2.16, p=0.087). This association remained statistically insignificant after adjusting for confounders, including BMI (OR 1.19, 95% CI 0.77–1.84, p=0.433). In women ≥35 years of age, 28% (n=44) and 20% (n=19), respectively, among cases and controls had fertility treatment (OR 1.60, 95% CI 0.87–2.94, p=0.132), and likewise, statistically insignificant after adjusting for confounders (OR 1.41, 95% CI 0.74–2.69, p<0.293).

Conclusion

In women with asthma and live births, our study revealed a trend towards an association between perennial allergy and a higher need for fertility treatment compared to seasonal/no allergy.

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<![CDATA[The (gradual) rise of memory inflation]]> https://www.researchpad.co/product?articleinfo=5b59abf1463d7e792f619092

Summary

Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to “exhaustion” the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T‐cell population structure which maintains functionality and size. In this review, I will discuss how the ideas around this form of memory have evolved over time and some new models which can help explain how these populations are induced and sustained. These models are relevant to immunity against persistent viruses, to novel vaccine strategies and to concepts about aging.

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<![CDATA[Age-related variations in the in vitro bactericidal activity of human sera against Pseudomonas aeruginosa]]> https://www.researchpad.co/product?articleinfo=5b593612463d7e589c54b6bc

The human serum is a vital component of the innate immunity of the host that acts as the first line of defence against invading pathogens. A key player in serum-mediated innate immune defence is a system of more than 35 proteins, collectively named as the complement system. After exposure of the pathogen, these proteins are activated in a cascade manner, ultimately forming a membrane attack complex (MAC) on the surface of the pathogen that directly lyses the bacterial cell. Formation of the MAC can be demonstrated in vitro by using serum bactericidal assay (SBA) that works in the absence of cellular components of blood after incubating the serum along with bacteria. Here, we describe the age-related differences in the bactericidal activity of human serum against Pseudomonas aeruginosa, an opportunistic human pathogen causing an array of hospital and community-acquired infections.

We demonstrate that adult sera were highly effective in the in vitro killing of Pseudomonas aeruginosa as compared to children and the elderly (p < 0.0001). Sera from children were seriously compromised in the killing P. aeruginosa, whereas elderly sera showed a reduced level of killing. Data revealed a positive correlation between age and serum-killing with higher coefficient of determination values of 0.34, 0.27, and 0.58 and p values of < 0.0001, < 0.001, and < 0.0001, respectively, after 60, 90, and 120 minutes of incubation. Hence, our study highlights the age-related difference in the bactericidal activity of human sera. We conclude that sera of children are totally compromised, whereas elderly sera are only partially compromised, in the killing of P. aeruginosa.

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<![CDATA[Hepatitis C virus cure does not impact kidney function decline in HIV co-infected patients]]> https://www.researchpad.co/product?articleinfo=5bfde5dcd5eed0c4846e2002

Supplemental Digital Content is available in the text

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<![CDATA[Implementing preexposure prophylaxis among key populations: an opportunity for patient-centered services and management of hepatitis B]]> https://www.researchpad.co/product?articleinfo=5bfde5dad5eed0c4846e1f81 ]]> <![CDATA[Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study]]> https://www.researchpad.co/product?articleinfo=5bfd2219d5eed0c48429c003

Objectives

Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).

Methods

The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. ‘Progressors’ were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).

Results

66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.

Conclusions

Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.

Trial registration number

NCT02339441.

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<![CDATA[Incidence of sexually transmitted infections before and after preexposure prophylaxis for HIV]]> https://www.researchpad.co/product?articleinfo=5bfc1e70d5eed0c484d85d9c

Objective:

Use of preexposure prophylaxis (PrEP) for HIV raises concerns about sexually transmitted infection (STI) incidence because of decreased condom use among MSM. This study examines whether PrEP is associated with STIs in the 12 months following PrEP prescription relative to the 12 months prior to PrEP and if STI rates are higher among PrEP users relative to individuals receiving postexposure prophylaxis (PEP).

Design:

Retrospective cohort study including PrEP users with more than 12 months of follow-up before PrEP prescription and individuals receiving PEP from 2010 to 2015 at Clinique l’Actuel (Montréal, Canada).

Methods:

Incidence of chlamydia, gonorrhoea, syphilis and hepatitis C virus over 12 months was compared before and after PrEP; and for PrEP versus PEP users using Poisson models to generate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted IRRs (aIRRs) controlling for frequency of STI-screening visits. Models comparing PrEP and PEP users were further adjusted for age and education.

Results:

One hundred and nine PrEP and 86 PEP users were included. Increased rates of STIs were observed in the 12 months after PrEP relative to the 12 months prior (IRR: 1.72, CI: 1.22–2.41; aIRR: 1.39, CI 0.98–1.96). PrEP users were also at higher STI risk relative to PEP users (IRR: 2.18, CI: 1.46–3.24; aIRR: 1.76, CI: 1.14–2.71).

Conclusion:

Increased rates of STIs among individuals after initiation of PrEP may suggest greater risk behaviours during the first year on PrEP. Further studies are needed to measure long-term trends in STI acquisition following PrEP initiation.

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<![CDATA[PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation]]> https://www.researchpad.co/product?articleinfo=5bfbe748d5eed0c484c816b5

Nobs et al. show that PPARγ drives pathogenic type-2 effector responses in the lung in both T cells and DCs by controlling IL-33–driven Th2 effector function and lung DC migration and Th2 priming capacity.

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<![CDATA[Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation]]> https://www.researchpad.co/product?articleinfo=5bfbe746d5eed0c484c81640

Hosomi et al. show that intestinal epithelial cell–specific deletion of X-box–binding protein 1, an unfolded protein response–related transcription factor, results in CHOP-dependent increased expression of specific natural killer group 2 member D (NKG2D) ligands. This activates NKG2D-expressing intraepithelial group 1 ILCs and promotes small intestinal inflammation.

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<![CDATA[Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation]]> https://www.researchpad.co/product?articleinfo=5bfbe741d5eed0c484c814ce

Kang et al. showed that reduced vaccinia-related kinase 3 (VRK3) expression affects synaptic structure and function and results in cognitive dysfunction and autism-like behaviors in mice. TrkB stimulation reverses the altered synaptic properties and restores autism-like behaviors in VRK3-deficient mice.

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<![CDATA[Transient apoptosis inhibition in donor stem cells improves hematopoietic stem cell transplantation]]> https://www.researchpad.co/product?articleinfo=5bfbe743d5eed0c484c8154c

Kollek et al. show that transient inhibition of apoptosis by short-term BCL-XL overexpression increases the viability of hematopoietic stem cells (HSCs) during engraftment and improves the outcome of HSC transplantation without signs of adverse pathologies. This strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.

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<![CDATA[Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program]]> https://www.researchpad.co/product?articleinfo=5bfbe744d5eed0c484c815c0

B cell specification requires the establishment of accessible transcriptional enhancers and promoters by lineage-specific transcription factors. Loughran et al. show that Mbd3/NuRD chromatin remodeling restricts the accessibility of these regions and therefore controls B versus T cell lineage fate by preventing B cell programming transcription factors from prematurely enacting lineage commitment.

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<![CDATA[LRRK2 promotes the activation of NLRC4 inflammasome during Salmonella Typhimurium infection]]> https://www.researchpad.co/product?articleinfo=5bfbe74cd5eed0c484c81796

LRRK2 is a serine/threonine protein kinase previously implicated in immunity against intracellular pathogens. In this study, Liu et al. report that LRRK2 promotes the host defense against Salmonella Typhimurium infection by phosphorylating NLRC4 at Ser533, thereby promoting the activation of NLRC4 inflammasome.

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<![CDATA[Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies]]> https://www.researchpad.co/product?articleinfo=5bfbe74dd5eed0c484c81823

Tanaka et al. show that BCL6 corepressor (BCOR) targets a significant portion of NOTCH1 targets in thymocytes to restrain their activation. Conditional deletion of the BCL6-binding domain of BCOR results in induction of Notch-dependent acute T-cell lymphoblastic leukemia in mice.

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<![CDATA[IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite–induced asthma models]]> https://www.researchpad.co/product?articleinfo=5bfbe74ad5eed0c484c81720

Ito et al. show that IL-22, which is produced mainly by CD4+ T cells, induces Reg3γ expression from lung epithelial cells through STAT3 activation and suppresses allergic airway inflammation via the inhibition of epithelial cytokine production.

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<![CDATA[Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells]]> https://www.researchpad.co/product?articleinfo=5bf9b43fd5eed0c4843d48f9

Seki and Rutz describe an optimized Cas9/RNP transfection approach to enable highly efficient CRISPR-mediated gene knockout in primary mouse and human T cells without T cell receptor stimulation that results in near complete loss of target gene expression at the population level.

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<![CDATA[A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets]]> https://www.researchpad.co/product?articleinfo=5bf9b441d5eed0c4843d4929

Álvarez-Prado et al. report a detailed map of AID-induced off-target mutations and identify molecular features that predict gene mutability. They identify a novel AID hotspot and demonstrate that base excision and mismatch repair back up each other to repair most AID deamination events.

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<![CDATA[Correction: STAT4 and T-bet control follicular helper T cell development in viral infections]]> https://www.researchpad.co/product?articleinfo=5bf9b43ed5eed0c4843d48c2 ]]> <![CDATA[Correction: Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease]]> https://www.researchpad.co/product?articleinfo=5bf9b43ad5eed0c4843d4821 ]]> <![CDATA[Correction: Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity]]> https://www.researchpad.co/product?articleinfo=5bf9b43cd5eed0c4843d4894 ]]>