PeerJ Preprints: Allergy and Clinical Immunologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=3200Allergy and Clinical Immunology articles published in PeerJ PreprintsGene/environment interaction and autoimmune diseasehttps://peerj.com/preprints/279392019-09-052019-09-05Tamia A HarrisShai Bel
Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both genetic and environmental factors contribute to the development and progression of these diseases. Nevertheless, genetic and environmental factors alone cannot explain a large proportion of cases, leading to the possibility that the two factors interact in driving disease onset. Understanding how genetic and environmental factor influence host physiology in a manner that leads to the development of autoimmune diseases can reveal the mechanisms by which these diseases manifest, and bring us closer to finding a cure for them. In this chapter, we will review the current research of genetic/environmental interactions that contribute to development of autoimmune diseases, with an emphasis on interactions between the host and the multitudes of microbes that inhabit it, the microbiota.
Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both genetic and environmental factors contribute to the development and progression of these diseases. Nevertheless, genetic and environmental factors alone cannot explain a large proportion of cases, leading to the possibility that the two factors interact in driving disease onset. Understanding how genetic and environmental factor influence host physiology in a manner that leads to the development of autoimmune diseases can reveal the mechanisms by which these diseases manifest, and bring us closer to finding a cure for them. In this chapter, we will review the current research of genetic/environmental interactions that contribute to development of autoimmune diseases, with an emphasis on interactions between the host and the multitudes of microbes that inhabit it, the microbiota.Approach to a highly-virulent emerging viral epidemic: A thought experiment and literature reviewhttps://peerj.com/preprints/275182019-02-052019-02-05Mohamed AmgadYousef A FouadMaha AT Elsebaie
What are the immunological facets of a highly successful viral epidemic, and what are likely successful strategies that can be used to counter its spread? Unlike many challenges in biology and public policy, viral epidemics are unique in that they require swift response, and quick application of existing knowledge to infer the underlying biology of a new pathological agent. This essay contextualizes the experience and findings from the viral immunology literature to respond to a hypothetical (yet likely) emerging viral epidemic. It begins with a review of the causes of some defining features of highly virulent viral epidemics, including causes of mortality, viral virulence, and immune evasion and suppression tactics. We provide an overview of lines of investigation to characterize emerging viral epidemics, including a brief survey of clinical and biological assays for immune surveillance and in-depth interrogation of viral biology. Finally, we provide a broad overview of management and vaccine development response strategies.
What are the immunological facets of a highly successful viral epidemic, and what are likely successful strategies that can be used to counter its spread? Unlike many challenges in biology and public policy, viral epidemics are unique in that they require swift response, and quick application of existing knowledge to infer the underlying biology of a new pathological agent. This essay contextualizes the experience and findings from the viral immunology literature to respond to a hypothetical (yet likely) emerging viral epidemic. It begins with a review of the causes of some defining features of highly virulent viral epidemics, including causes of mortality, viral virulence, and immune evasion and suppression tactics. We provide an overview of lines of investigation to characterize emerging viral epidemics, including a brief survey of clinical and biological assays for immune surveillance and in-depth interrogation of viral biology. Finally, we provide a broad overview of management and vaccine development response strategies.Variant analysis of RNA sequences in severe equine asthmahttps://peerj.com/preprints/34912018-08-292018-08-29Laurence TessierOlivier CôtéDorothee Bienzle
Background. Severe equine asthma is a chronic inflammatory disease of the lung in horses similar to low-Th2 late-onset asthma in humans. This study aimed to determine the utility of RNA-Seq to call gene sequence variants, and to identify sequence variants or potential relevance to the pathogenesis of asthma. Methods. RNA-Seq data were generated from endobronchial biopsies collected from 6 asthmatic and 7 non-asthmatic horses before and after challenge (26 samples total). Sequences were aligned to the equine genome with Spliced Transcripts Alignment to Reference software. Read preparation for sequence variant calling was performed with Picard tools and Genome Analysis Toolkit (GATK). Sequence variants were called and filtered using GATK and Ensembl Variant Effect Predictor (VEP) tools, and two RNA-Seq predicted sequence variants were investigated with both PCR and Sanger sequencing. Supplementary analysis of novel sequence variant selection with VEP was based on a score of <0.01 predicted with Sorting Intolerant From Tolerant (SIFT) software, missense nature, location within the protein coding sequence and presence in all asthmatic individuals. For select variants, effect on protein function was assessed with Polymorphism Phenotyping (PolyPhen) 2 and Screening for Non-Acceptable Polymorphism (SNAP) 2 software. Sequences were aligned and 3D protein structures predicted with Geneious software. Difference in allele frequency between the groups was assessed using a Pearson's Chi-squared test with Yates' continuity correction, and difference in genotype frequency was calculated using the Fisher's exact test for count data. Results. RNA-Seq variant calling and filtering correctly identified substitution variants in PACRG and RTTN. Sanger sequencing confirmed that the PACRG substitution was appropriately identified in all 26 samples while the RTTN substitution was identified correctly in 24 of 26 samples. These variants of uncertain significance had substitutions that were predicted to result in loss of function and to be non-neutral. Amino acid substitutions projected no change of hydrophobicity and isoelectric point in PACRG, and a change in both for RTTN. For PACRG, no difference in allele frequency between the two groups was detected but a higher proportion of asthmatic horses had the altered RTTN allele compared to non-asthmatic animals. Discussion. RNA-Seq was sensitive and specific for calling gene sequence variants in this disease model. Even moderate coverage (<10-20 cpm) yielded correct identification in 92% of samples, suggesting RNA-Seq may be suitable to detect sequence variants in low coverage samples. The impact of amino acid alterations in PACRG and RTTN proteins, and possible association of the sequence variants with asthma, is of uncertain significance, but their role in ciliary function may be of future interest.
Background. Severe equine asthma is a chronic inflammatory disease of the lung in horses similar to low-Th2 late-onset asthma in humans. This study aimed to determine the utility of RNA-Seq to call gene sequence variants, and to identify sequence variants or potential relevance to the pathogenesis of asthma. Methods. RNA-Seq data were generated from endobronchial biopsies collected from 6 asthmatic and 7 non-asthmatic horses before and after challenge (26 samples total). Sequences were aligned to the equine genome with Spliced Transcripts Alignment to Reference software. Read preparation for sequence variant calling was performed with Picard tools and Genome Analysis Toolkit (GATK). Sequence variants were called and filtered using GATK and Ensembl Variant Effect Predictor (VEP) tools, and two RNA-Seq predicted sequence variants were investigated with both PCR and Sanger sequencing. Supplementary analysis of novel sequence variant selection with VEP was based on a score of <0.01 predicted with Sorting Intolerant From Tolerant (SIFT) software, missense nature, location within the protein coding sequence and presence in all asthmatic individuals. For select variants, effect on protein function was assessed with Polymorphism Phenotyping (PolyPhen) 2 and Screening for Non-Acceptable Polymorphism (SNAP) 2 software. Sequences were aligned and 3D protein structures predicted with Geneious software. Difference in allele frequency between the groups was assessed using a Pearson's Chi-squared test with Yates' continuity correction, and difference in genotype frequency was calculated using the Fisher's exact test for count data. Results. RNA-Seq variant calling and filtering correctly identified substitution variants in PACRG and RTTN. Sanger sequencing confirmed that the PACRG substitution was appropriately identified in all 26 samples while the RTTN substitution was identified correctly in 24 of 26 samples. These variants of uncertain significance had substitutions that were predicted to result in loss of function and to be non-neutral. Amino acid substitutions projected no change of hydrophobicity and isoelectric point in PACRG, and a change in both for RTTN. For PACRG, no difference in allele frequency between the two groups was detected but a higher proportion of asthmatic horses had the altered RTTN allele compared to non-asthmatic animals. Discussion. RNA-Seq was sensitive and specific for calling gene sequence variants in this disease model. Even moderate coverage (<10-20 cpm) yielded correct identification in 92% of samples, suggesting RNA-Seq may be suitable to detect sequence variants in low coverage samples. The impact of amino acid alterations in PACRG and RTTN proteins, and possible association of the sequence variants with asthma, is of uncertain significance, but their role in ciliary function may be of future interest.Cytokine regulation of stem cellshttps://peerj.com/preprints/23472016-08-092016-08-09Gyanesh SinghHasan Korkaya
Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.
Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.Suspected anaphylaxis from intravenous cefazolin during general anaesthesia in a doghttps://peerj.com/preprints/22752016-07-112016-07-11Melanie PrebbleDaniel SJ Pang
A 6-year-old female Shetland Sheepdog with a history of cardiorespiratory compromise during general anaesthesia was referred for ovariohysterectomy surgery. Clinical examination was unremarkable at presentation and physiologic parameters under general anaesthesia were within expected ranges during preparation for surgery. Shortly after completion of an intravenous injection of cefazolin, the audible signal from the Doppler ultrasound unit stopped. A rapid survey of the patient revealed tachycardia with weak femoral pulses, tachypnoea, hyperpnoea and substantially increased resistance to manual positive pressure ventilation. Stopping inhalant anaesthesia, administering salbutamol, corticosteroids and diphenhydramine were associated with resolution of clinical signs. However, marked hypotension and resistance to ventilation recurred approximately 25 minutes later. Low dose intravenous epinephrine (5 mcg/kg) was effective at increasing arterial blood pressure and reversing respiratory dysfunction. Surgery was completed and the patient recovered uneventfully. Initial reliance on second line therapy and delay in administering epinephrine, the recommended treatment for anaphylaxis, may have slowed resolution of clinical signs.
A 6-year-old female Shetland Sheepdog with a history of cardiorespiratory compromise during general anaesthesia was referred for ovariohysterectomy surgery. Clinical examination was unremarkable at presentation and physiologic parameters under general anaesthesia were within expected ranges during preparation for surgery. Shortly after completion of an intravenous injection of cefazolin, the audible signal from the Doppler ultrasound unit stopped. A rapid survey of the patient revealed tachycardia with weak femoral pulses, tachypnoea, hyperpnoea and substantially increased resistance to manual positive pressure ventilation. Stopping inhalant anaesthesia, administering salbutamol, corticosteroids and diphenhydramine were associated with resolution of clinical signs. However, marked hypotension and resistance to ventilation recurred approximately 25 minutes later. Low dose intravenous epinephrine (5 mcg/kg) was effective at increasing arterial blood pressure and reversing respiratory dysfunction. Surgery was completed and the patient recovered uneventfully. Initial reliance on second line therapy and delay in administering epinephrine, the recommended treatment for anaphylaxis, may have slowed resolution of clinical signs.Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitishttps://peerj.com/preprints/9722015-04-102015-04-10Emilio BesadaWenche KoldingsnesJohannes C Nossent
Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.
Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.MicroRNAs expression profile in CCR6+ regulatory T cellshttps://peerj.com/preprints/471v22014-08-222014-08-22Juanjuan ZhaoYongju LiYan HuChao ChenYa ZhouYijin TaoMengmeng GuoNalin QinLin Xu
Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.
Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.Pneumocystis jiroveci pneumonia prophylaxis is a challenge in granulomatosis with polyangiitis patients treated with rituximab.https://peerj.com/preprints/149v12013-12-112013-12-11Emilio Besada
All strategies to prevent Pneumocystis jiroveci pneumonia (PCP) during rituximab treatment have their rationale in patients with granulomatosis with polyangiitis (GPA) and to some extent in patients with other autoimmune diseases (AID). Risk factors of PCP and severe infections are very similar in GPA patients. The decision of PCP prophylaxis should not be limited at RTX initiation and during RTX treatment, but should be reassessed continuously in all GPA patients. Since PCP increases the mortality risk in GPA (and AID) patients, the treating physician should always consider PCP as a possible diagnosis in patients treated with RTX - receiving or not PCP prophylaxis.
All strategies to prevent Pneumocystis jiroveci pneumonia (PCP) during rituximab treatment have their rationale in patients with granulomatosis with polyangiitis (GPA) and to some extent in patients with other autoimmune diseases (AID). Risk factors of PCP and severe infections are very similar in GPA patients. The decision of PCP prophylaxis should not be limited at RTX initiation and during RTX treatment, but should be reassessed continuously in all GPA patients. Since PCP increases the mortality risk in GPA (and AID) patients, the treating physician should always consider PCP as a possible diagnosis in patients treated with RTX - receiving or not PCP prophylaxis.