Background: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. ...MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus. Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak. Findings: Sixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. Interpretation: A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms. Funding: This work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.
Work on the Wildside Ash, Zoe
Veterinary Nursing Journal,
12/1/2008, 2008-12-00, Letnik:
23, Številka:
12
Journal Article
This was it... just eight weeks after booking my trip of a lifetime I was standing at Gatwick Airport waving goodbye to my dad as I passed through the security gates. I was now alone. It was exciting ...and terrifying all at the same time, but from this moment on everything I had read about, all the photos I had seen and everything I had daydreamed about, became REALITY!...I WAS ON MY WAY TO SOUTH AFRICA!
Nail disease is a characteristic manifestation of the psoriatic disease spectrum but is poorly understood.
Given the intrinsically high spatial resolution imaging capabilities of optical coherence ...tomography (OCT), we assessed its value in psoriatic nail disease compared to high-resolution ultrasonography (US).
All fingernails in a psoriatic arthritis patient with nail changes were scanned with OCT, and findings were compared with high-resolution US.
US showed loss of trilaminar appearance in all nails, resulting in the nail plate being visualized as a single hyperechoic layer with inhomogeneous thickness. The OCT images showed much higher-resolution changes with prominent thickening in the ventral plate at the nail bed which was grossly inhomogeneous, 'eroded' and irregularly fused with the underlying epidermis, which correlated with the clinical observation of subungal hyperakeratosis.
OCT has considerable potential for the evaluation of psoriatic nail disease and may be superior to US.
Recently the role of several ligament and tendon insertions around the nail matrix and nail plate have been identified as possible contributory factors that explain the higher prevalence of nail ...involvement in psoriatic arthritis (PsA). The purpose of this study was to determine whether such anatomical factors might also be associated with different patterns of nail involvement in skin psoriasis and PsA.
A total of 173 patients were recruited: 121 PsA cases and 52 psoriasis cases. All patients had a standardised assessment of the nails for lesions including pitting, splinter haemorrhages and onycholysis.
The overall modified Nail Psoriasis Severity Index scores did not differ between the two groups (psoriasis mean 8.5, SD 7.1; PsA mean 8.3, SD 9.4). In the nail matrix, linear pitting appeared to be more common in skin psoriasis (OR 0.27, 95% CI 0.18-0.41). There were no significant differences in the distribution of nail plate abnormalities other than splinter haemorrhages which were more commonly seen in psoriasis cases (OR 0.23, 95% CI 0.14-0.39).
The pattern of nail disease in psoriasis and PsA differed with respect to the frequency of linear pitting and splinter haemorrhages, with both features occurring more often in psoriasis.
The role of enthesitis in the pathogenesis of psoriatic arthritis has been increasingly recognised in the last twenty years. High resolution imaging techniques and histology have shown that the ...distal interphalangeal (DIP) joint extensor tendon is directly anchored to the nail. More recently, it has become apparent that a significant proportion of asymptomatic psoriasis patients have subclinical enthesitis at sites such as the Achilles tendon. This thesis explored the hypothesis that nail disease without clinical arthritis was associated with DIP joint enthesopathy and that nail disease equated with remote systemic enthesopathy. Imaging studies utilising magnetic resonance imaging (MRI) of the DIP joint confirmed the relationship between enthesitis and nail disease in psoriatic arthritis, and found subtle enthesitis and osteitis in psoriasis patients. High resolution ultrasound that has an intrinsically greater resolution than MRI showed extensor tendon enthesopathy of the DIP to be common in psoriasis patients with nail disease, but not those without nail disease. It was also shown that nail disease in psoriasis patients without arthritis was associated with sonographically-determined remote enthesopathy in the lower limbs. In a small pilot study (N=9), despite clinical improvements MRI showed ongoing inflammation in and around the DIP joint after six months treatment with a TNF inhibitor. The long term outlook of DIP joint psoriatic arthritis was studied, with a review of a cohort of patients at a mean of nine years after a baseline MRI scan. This demonstrated joint space narrowing in the majority of patients. The development of arthritis mutilans or ankylosis was seen in a minority, but without a close correlation with baseline MRI findings. Collectively these findings show a link between nail disease in psoriasis patients and both local and systemic subclinical enthesopathy.
The role of enthesitis in the pathogenesis of psoriatic arthritis has been increasingly recognised in the last twenty years. High resolution imaging techniques and histology have shown that the ...distal interphalangeal (DIP) joint extensor tendon is directly anchored to the nail. More recently, it has become apparent that a significant proportion of asymptomatic psoriasis patients have subclinical enthesitis at sites such as the Achilles tendon. This thesis explored the hypothesis that nail disease without clinical arthritis was associated with DIP joint enthesopathy and that nail disease equated with remote systemic enthesopathy. Imaging studies utilising magnetic resonance imaging (MRI) of the DIP joint confirmed the relationship between enthesitis and nail disease in psoriatic arthritis, and found subtle enthesitis and osteitis in psoriasis patients. High resolution ultrasound that has an intrinsically greater resolution than MRI showed extensor tendon enthesopathy of the DIP to be common in psoriasis patients with nail disease, but not those without nail disease. It was also shown that nail disease in psoriasis patients without arthritis was associated with sonographically-determined remote enthesopathy in the lower limbs. In a small pilot study (N=9), despite clinical improvements MRI showed ongoing inflammation in and around the DIP joint after six months treatment with a TNF inhibitor. The long term outlook of DIP joint psoriatic arthritis was studied, with a review of a cohort of patients at a mean of nine years after a baseline MRI scan. This demonstrated joint space narrowing in the majority of patients. The development of arthritis mutilans or ankylosis was seen in a minority, but without a close correlation with baseline MRI findings. Collectively these findings show a link between nail disease in psoriasis patients and both local and systemic subclinical enthesopathy.
Permafrost, or permanently frozen ground, is a major C pool storing approximately 1672 Pg C. Upon warming, microorganisms in permafrost release greenhouse gases such as CO2 and CH4 via mineralization ...that accelerates warming climatic conditions. The Snowy Range Mountains, located west of Laramie, Wyoming contain all the required conditions for permafrost to exist. After initial field observations, permafrost was not found despite the presence of periglacial features and anecdotal evidence of once frozen ground at the study site. High-alpine ecosystems provide numerous ecosystem services that, under changing climatic conditions, could alter downstream processes in the context of thawing cold soils. These ecosystems also represent an understudied area of soil science, relict high-alpine permafrost soils. To investigate whether high-alpine soils once affected by permafrost will respond differently to warming temperatures, a pedological, mineralogical, and microbiological investigation into the recently thawed high-alpine permafrost soils was conducted to better understand the soil-carbon response after recent warming. Results confirm pedological evidence of active cryoturbation in patterned ground soils, and a large input of loess into the system. These findings show that these soils are still developing under drastic seasonal temperature changes and are receiving an input of soil from nearby basins, thus affecting the soil microbial ecosystem and the soil-carbon feedback loop. Microbial activity in patterned ground soils was compared to nearby meadow soils to understand if there was a difference in microbial response via mineralizable C and enzyme assays. Mineralizable C in patterned ground was generally higher than in meadow soils, but not significantly different. Including organic carbon into the calculations resulted in flipped trends between patterned ground and meadow mineralization, with meadow have higher mineralizable C. Potential extracellular enzyme activity results confirmed there is significantly higher enzyme activity in meadow versus patterned ground soils. Results from mineralizable C and enzyme assays indicate that, compared to alpine meadow soils, there may be more complex forms of C remaining in patterned ground soils still largely affected by low temperatures, thus limiting activity of soil microorganisms. Together, our results provide an improved understanding of patterned ground soils in high-alpine ecosystems and an improved picture of post permafrost thaw in high-alpine systems as influenced by soil evolution and microbial ecology.
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