Fulminant onset of insulin-dependent diabetes with positive anti-GAD antibody titers during treatment with nivolumab in a patient with NSCLC

Abstract

Programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) inhibitors have been highlighted in the field of cancer treatment. The interaction between PD-1 and PD-L1 is thought to play an important role in the regulation of the self-immune tolerance mechanism, so blocking these molecules may cause serious immune-related adverse events (IrAE), including fulminant insulin-dependent (type 1) diabetes. Here, we describe a patient with fulminant type 1 diabetes induced by nivolumab, an anti-PD-1 antibody. The patient, a 78-year-old man, was being treated with nivolumab as a third-line treatment for squamous cell carcinoma of the lung. After three cycles, he experienced an abrupt flare-up of the blood glucose within half a day. His blood glucose further increased without clinical symptoms until his hospital visit. Laboratory data showed the complete exhaustion of intrinsic insulin and the elevation of serum antibody titer to glutamic acid decarboxylase (GAD). Although the patient was previously diagnosed with non-insulin-dependent (type 2) diabetes, his disease activity had been well controlled with oral medication and low-dose insulin therapy until just before the flare-up. Because of the laboratory findings and the extremely rapid onset of hyperglycemia, a diagnosis of fulminant, rather than the rapid onset, type 1 diabetes related to nivolumab therapy was strongly suspected. Our case study indicates that fulminant hyperglycemia can occur extremely rapidly. The blood glucose of patients receiving PD-1 antibody therapy should be closely monitored.

https://ift.tt/2N77L4a

ACPA mediates the interplay between innate and adaptive immunity in rheumatoid arthritis

Publication date: Available online 11 July 2018

Source: Autoimmunity Reviews

Author(s): Xiwen Dong, Zhaohui Zheng, Yue Zhai, Yan Zheng, Jin Ding, Jianli Jiang, Ping Zhu

Abstract

The production of anti-citrullinated peptide antibodies (ACPAs) requires the participation of both innate immunity and adaptive immunity. On the one hand, activated innate immunity is able to produce citrullinated auto-antigens that fuel autoimmunity and provide an inflammatory environment that facilitates the breach of self-tolerance, proliferation of self-reactive T/B cells and the production of ACPAs. On the other hand, after their production by plasma B cells, ACPAs are also able to interact with innate immunity to exacerbate the manifestation and chronicity of rheumatoid arthritis (RA). This article discusses the roles of citrullinated peptides and ACPA played in innate immunity and autoimmunity. In addition, we emphasise the relationships between environmental factors and innate immunity, as well as the pathogenic function of ACPAs per se. In doing so, we hope to provide fundamental knowledge of RA pathogenesis and reveal potential therapeutic targets in RA treatment.

https://ift.tt/2mbadeE

Support of precision medicine through risk-stratification in autoimmune liver diseases – histology, scoring systems, and non-invasive markers

Publication date: Available online 11 July 2018

Source: Autoimmunity Reviews

Author(s): Lars Bossen, Alessio Gerussi, Vasiliki Lygoura, George F. Mells, Marco Carbone, Pietro Invernizzi

Abstract

Autoimmune liver diseases (AILDs) are complex conditions, which arise from the interaction between a genetic susceptibility and unknown environmental triggers. They represent a relevant cause of liver failure and liver transplantation worldwide. As a testimony of our progress in understanding the biology of AILDs and the disease progression is the overall median survival which has increased over the last decade. However, there are still major challenges such as the lack of therapies and surveillance strategies in primary sclerosing cholangitis (PSC), the management and treatment of non-responders to first-line therapies in primary biliary cholangitis (PBC) and the need for tailoring immunosuppressive drugs in autoimmune hepatitis (AIH). The different disease course and treatment response in patients with AILDs might be related to a heterogeneous genetic background between individuals which translates in a heterogeneous clinical phenotype. Thus, it becomes essential to personalise management and treatment based on specific risk profiles, e.g. low-risk and high-risk, based on genetic and molecular signatures.

It is now possible, thanks to the development of large-scale AILDs patient cohorts, that such diseases can be analysed using various high-throughput methods like gene expression profiling, next generation sequencing and other omics technologies to identify unique fingerprints based on which a personalised or tailor-made management and therapy can be developed. The final aim being to facilitate treatment decision-making that balances patient-specific risks and preferences. This is critical especially now with the current and forthcoming availability of more efficacious medications. To reach this point we need specific interventions such as creating bigger biobanks, sequencing more genomes and linking biological information to health-related data.

We have already identified subsets of patients with different risk profiles among patients with PBC, PSC and AIH by using clinical tools such as liver histology, laboratory investigation and non-invasive methods. In this manuscript, we review the clinical features and investigations that already enable us to individualize the care of PBC patients and that might support the development of precision medicine (PM) in AILDs.

https://ift.tt/2zzZZOa

ACPA mediates the interplay between innate and adaptive immunity in rheumatoid arthritis

Publication date: Available online 11 July 2018

Source: Autoimmunity Reviews

Author(s): Xiwen Dong, Zhaohui Zheng, Yue Zhai, Yan Zheng, Jin Ding, Jianli Jiang, Ping Zhu

Abstract

The production of anti-citrullinated peptide antibodies (ACPAs) requires the participation of both innate immunity and adaptive immunity. On the one hand, activated innate immunity is able to produce citrullinated auto-antigens that fuel autoimmunity and provide an inflammatory environment that facilitates the breach of self-tolerance, proliferation of self-reactive T/B cells and the production of ACPAs. On the other hand, after their production by plasma B cells, ACPAs are also able to interact with innate immunity to exacerbate the manifestation and chronicity of rheumatoid arthritis (RA). This article discusses the roles of citrullinated peptides and ACPA played in innate immunity and autoimmunity. In addition, we emphasise the relationships between environmental factors and innate immunity, as well as the pathogenic function of ACPAs per se. In doing so, we hope to provide fundamental knowledge of RA pathogenesis and reveal potential therapeutic targets in RA treatment.

https://ift.tt/2mbadeE

Support of precision medicine through risk-stratification in autoimmune liver diseases – histology, scoring systems, and non-invasive markers

Publication date: Available online 11 July 2018

Source: Autoimmunity Reviews

Author(s): Lars Bossen, Alessio Gerussi, Vasiliki Lygoura, George F. Mells, Marco Carbone, Pietro Invernizzi

Abstract

Autoimmune liver diseases (AILDs) are complex conditions, which arise from the interaction between a genetic susceptibility and unknown environmental triggers. They represent a relevant cause of liver failure and liver transplantation worldwide. As a testimony of our progress in understanding the biology of AILDs and the disease progression is the overall median survival which has increased over the last decade. However, there are still major challenges such as the lack of therapies and surveillance strategies in primary sclerosing cholangitis (PSC), the management and treatment of non-responders to first-line therapies in primary biliary cholangitis (PBC) and the need for tailoring immunosuppressive drugs in autoimmune hepatitis (AIH). The different disease course and treatment response in patients with AILDs might be related to a heterogeneous genetic background between individuals which translates in a heterogeneous clinical phenotype. Thus, it becomes essential to personalise management and treatment based on specific risk profiles, e.g. low-risk and high-risk, based on genetic and molecular signatures.

It is now possible, thanks to the development of large-scale AILDs patient cohorts, that such diseases can be analysed using various high-throughput methods like gene expression profiling, next generation sequencing and other omics technologies to identify unique fingerprints based on which a personalised or tailor-made management and therapy can be developed. The final aim being to facilitate treatment decision-making that balances patient-specific risks and preferences. This is critical especially now with the current and forthcoming availability of more efficacious medications. To reach this point we need specific interventions such as creating bigger biobanks, sequencing more genomes and linking biological information to health-related data.

We have already identified subsets of patients with different risk profiles among patients with PBC, PSC and AIH by using clinical tools such as liver histology, laboratory investigation and non-invasive methods. In this manuscript, we review the clinical features and investigations that already enable us to individualize the care of PBC patients and that might support the development of precision medicine (PM) in AILDs.

https://ift.tt/2zzZZOa

Endotypes of Chronic Rhinosinusitis Across Ancestry and Geographic Regions

Abstract

Purpose of Review

Preliminary studies have suggested differences in endotypes of chronic rhinosinusitis (CRS) across ancestry/ethnic groups. Eosinophilic CRS (ECRS) is the predominant subtype for Western/European ancestry CRS patients and non-eosinophilic CRS (nECRS) for Asian patients. This review aims to re-analyze CRS endotypes across ancestry populations using one consistent criteria to existing data.

Recent Findings

Although tissue eosinophilia is the most commonly used criterion for ECRS, various cut-off points are suggested. Surrogate markers have been extensively studied. Sixty-six cohorts with study criteria were included with a total of 8557 patients. Raw data from 11 studies 544 patients were re-analyzed using number of tissue eosinophils. At lower cut-off values of ≥ 5 and ≥ 10 cells/HPF, most patients of Asian and Western/European ancestry were classified as ECRS without difference. In contrast, at cut-off points of ≥ 70 and ≥ 120 cells/HPF, the majority of both groups became reclassified as nECRS.

Summary

After applying one consistent criteria to existing data, differences across ancestry and geographic populations in endotypes of CRS were no longer evident.

https://ift.tt/2ujYA8M

Is Allergen Immunotherapy in Children Disease Modifying? A Review of the Evidence

Abstract

Purpose of Review

Although evidence supports a beneficial effect of allergen immunotherapy on the symptoms of allergic respiratory disease and food allergy, it is not clear whether immunotherapy modifies the natural history of these conditions.

Recent Findings

In aeroallergen immunotherapy, studies suggest that prevention of asthma can be attained. Less evident is the ability of immunotherapy to prevent new allergen sensitizations and more studies are needed to test whether immunotherapy can continue suppressing airway symptoms after treatment discontinuation. In food allergen immunotherapy, there is evidence that unresponsiveness to a food challenge can be sustained in some treatment recipients, but little knowledge exists as to the dose and duration of treatment that can optimize this effect.

Summary

Suggestive evidence exists that allergen immunotherapy can modify allergic disease in children, but definitive studies are lacking. More research in the field is required.

https://ift.tt/2N78Gl8