The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Abstract

Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.

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Dendritic cells in central nervous system autoimmunity

Abstract

Dendritic cells (DCs) operate at the intersection of the innate and adaptive immune systems. DCs can promote or inhibit adaptive immune responses against neuroantigens. While DC intrinsic properties, i.e., their maturation state or the subset they belong to, are important determinants of the outcome of an autoimmune reaction, tissue-specific cues might also be relevant for the function of DCs. Thus, a better understanding of the performance of distinct DC subsets in specific anatomical niches, not only in lymphoid tissue but also in non-lymphoid tissues such as the meninges, the choroid plexus, and the inflamed CNS parenchyma, will be instrumental for the design of immune intervention strategies to chronic inflammatory diseases that do not put at risk basic surveillance functions of the immune system in the CNS. Here, we will review modern concepts of DC biology in steady state and during autoimmune neuroinflammation.

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Repair of complex pharyngocutaneous fistula using a staged temporoparietal fascial flap

Publication date: Available online 25 November 2016
Source:American Journal of Otolaryngology
Author(s): Nicholas B. Abt, Priya Srikanth, Sidharth V. Puram, Daniel G. Deschler
IntroductionPCF is the most common major complication after salvage total laryngectomy (TL), especially for previously irradiated patients with laryngeal or hypopharyngeal cancer.Methods/resultsA 65-year-old woman presented with recurrent bilateral supraglottic SCC requiring salvage TL 5.5years after initial T1N0M0 epiglottic SCC resection. Her post-operative course was complicated by PCF development one month post-operatively and surgical fistula closure was delayed for adjuvant chemoradiotherapy. The fistula persisted despite local wound therapy, several primary closures, pectoralis flap reconstruction with multiple revisions, and extensive hyperbaric oxygen treatments. Given her prior history, she underwent a staged right temporoparietal fascial flap reconstruction for persistent complex fistula, with second-stage flap takedown and complete inset of the TPFF skin island into the PCF.ConclusionThis case demonstrates the utility of staged TPFF in complex PCF repair, with minimal morbidity, especially in a patient with prior irradiation and flap use that complicates tissue availability.



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Prospective, multicenter evaluation of balloon sinus dilation for treatment of pediatric chronic rhinosinusitis

Background

Although balloon sinus dilation is a treatment option for adults with chronic rhinosinusitis (CRS), there have been few studies performed in pediatric patients.

Methods

This study was designed as a prospective, multicenter, single-arm investigation. Children (2 to 21 years old) with CRS who had failed medical management were treated with balloon sinus dilation and followed to 6 months postprocedure.

Results

Fifty children were treated at 4 centers; 33 participants were 2 to 12 years old (mean ± standard deviation age: 6.6 ± 2.2 years) and 17 participants were >12 to 21 years (mean age: 15.7 ± 2.5 years). A total of 157 sinus dilations were attempted (98 maxillary, 30 frontal, and 29 sphenoid sinuses) and all were successful with no complications. Significant improvement in the Sinus and Nasal Quality of Life Survey (SN-5) was seen for all children between baseline and 6 months (4.6 ± 1.2 vs 1.7 ± 0.8; p < 0.0001) and 92% improved by a minimal clinically important difference (MCID) of 1.0 or more. Those children aged 2 to 12 years with standalone balloon dilation also showed significant SN-5 improvements between baseline and follow-up (4.5 ± 1.0 vs 1.9 ± 0.8; p < 0.0001). Multivariate regression analysis showed no differences or associations of SN-5 improvement at 6 months with the presence of allergy, asthma, or concomitant procedures. For adolescents, overall 22-item Sino-Nasal Outcome Test (SNOT-22) mean scores were also significantly improved at 6 months (42.2 ± 19.2 vs 10.4 ± 9.7; p < 0.0001).

Conclusion

Balloon sinus dilation is safe and appears effective for children with CRS aged 2 years and older.

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Olfaction in patients with allergic rhinitis: an indicator of successful MP-AzeFlu therapy

Background

The purpose of this study was to investigate the effect of MP-AzeFlu on olfaction and the interaction between severity of allergic rhinitis and olfactory improvement after therapy.

Methods

A prospective, multicenter, observational study was performed on 47 patients with persistent allergic rhinitis. Duration and severity of allergic rhinitis was diagnosed and classified using the modified Allergic Rhinitis and its Impact on Asthma (ARIA) criteria and the proof of allergen sensitization from positive skin-prick tests, specific immonoglobulin E (IgE) in serum, and nasal provocation response. Patients were treated with MP-AzeFlu (1 spray/nostril twice daily) over 3 months. Olfactory function was assessed at baseline and at 1 and 3 months of therapy using the "Sniffin' Sticks" test. In addition, a nasal symptom score was recorded on a visual analog scale (VAS) at each given time-point.

Results

MP-AzeFlu was found to be associated with a significant improvement in TDI score, from 23.7 at baseline to 34.2 at 1 month (p < 0.001) and 37.1 at 3 months (p < 0.001) of treatment. Furthermore, a highly significant improvement of symptoms over time (p < 0.001; VAS at baseline: 84.3; 1 month: 32.4; 3 months: 26.2) could be demonstrated. Most importantly, there was a highly significant interaction between the severity of allergic rhinitis and olfactory function (p < 0.001) and VAS (p < 0.001).

Conclusion

MP-AzeFlu is associated with olfactory improvement in persistent allergic rhinitis patients. Further, the modified ARIA severity classification is an indicator of patients' olfactory function. Moreover, assessment of olfaction seems to be a reliable indicator of the clinical success of antiallergic/antiinflammatory therapy.

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Correlation between the number of allergen sensitizations and immunoglobulin E: monosensitization vs polysensitization

Background

The purpose of this study was to determine if total serum immunoglobulin E (IgE) could predict monosensitization compared to polysensitization in patients with allergic rhinitis (AR).

Methods

This was a retrospective study of a cohort of 1073 patients who underwent allergy testing. Differences in total IgE level between unsensitized, monosensitized, and polysensitized subjects were calculated. Pearson correlation coefficient was calculated to determine whether there was a relationship between total IgE level and the number of positive allergen sensitizations. In addition, allergen sensitization class was calculated for each allergen sensitization and totaled for each patient. Pearson correlation coefficient was calculated to determine the relationship between total IgE level and weighted allergen sensitization by class.

Results

There were 159 patients who were monosensitized compared to 492 patients who were polysensitized. Of the monosensitized patients, almost 50% (74) were sensitized to one or both dust mites. Total IgE was higher in polysensitized patients compared to monosensitized compared to controls (p < 0.001). Pearson correlation coefficient between total IgE and number of positive allergen sensitizations was 0.465 (p ≤ 0.001). Pearson correlation coefficient between total IgE and allergen class–weighted sensitizations was 0.529 (p ≤ 0.001).

Conclusion

IgE level can be used to predict monosensitization vs polysensitization. There is a moderate correlation between total IgE sensitization and the number of positive allergen sensitizations, as well as allergen class–weighted sensitizations.

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Histamine H4 receptor gene polymorphisms: a potential predictor of oral H1 antihistamine efficacy for allergic rhinitis

Background

Our study aimed to investigate the associations between Histamine H4 receptor (HRH4) gene polymorphisms (rs77485247, rs74604924, and rs77041280) and oral H1 antihistamine efficacy for the treatment of allergic rhinitis (AR) patients.

Methods

A total of 142 AR patients were selected as a case group and 160 healthy individuals were recruited as a control group. Single nucleotide polymorphisms (SNPs) in the HRH4 gene were detected using direct sequencing. Serum immunoglobulin E (IgE), specific IgE, and eosinophil cationic protein (ECP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Clinical efficacy was evaluated by the visual analogue scale (VAS). The occurrence of adverse reaction was recorded.

Results

There were significant differences in the distribution frequencies of mutant genotype (TA + AA) and A allele of rs77485247, mutant genotype (AT + TT) and T allele of rs74604924, and mutant genotype (AT + TT) and T allele of rs77041280 between the case and control groups. AR patients with mutant genotype (TA + AA) of rs77485247 and AR patients with mutant genotype (AT + TT) of rs77041280 had higher specific IgE, ECP levels, and VAS scores after treatment and lower incidence of adverse reactions and total effective rate than those with TT genotype and those with AA genotype, respectively. However, for rs74604924, there were no differences was found between AR patients with mutant genotype (AT + TT) and those with AA genotype.

Conclusion

Our findings provide evidence that HRH4 rs77485247 and rs77041280 polymorphisms may be associated with the risk of AR and the efficacy of H1 antihistamines for the treatment of AR patients.

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