scholarly journals Establishing the prevalence of common, clinically relevant tissue-specific autoantibodies following SARS CoV-2 infection

Author(s):  
A. G. Richter ◽  
Adrian Shields ◽  
Abid Karim ◽  
David Birch ◽  
Sian Faustini ◽  
...  

COVID-19 has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand this phenomenon in more detail, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS-CoV-2, suffering from COVID-19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on ITU for non COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID-19 ITU group compared with non-COVID-19 ITU disease control patients and that autoantibodies were also found in the serum 3-5 months post COVID-19 infection. Non-COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID-19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that severe COVID-19 induces a pattern of autoantibodies that may correlate with and contribute to the immune pathology associated with the long-term sequelae of infection.

2000 ◽  
Vol 278 (3) ◽  
pp. R705-R711 ◽  
Author(s):  
T. A. McAllister ◽  
J. R. Thompson ◽  
S. E. Samuels

The effect of long-term cold exposure on skeletal and cardiac muscle protein turnover was investigated in young growing animals. Two groups of 36 male 28-day-old rats were maintained at either 5°C (cold) or 25°C (control). Rates of protein synthesis and degradation were measured in vivo on days 5, 10, 15, and 20. Protein mass by day 20 was ∼28% lower in skeletal muscle (gastrocnemius and soleus) and ∼24% higher in heart in cold compared with control rats ( P < 0.05). In skeletal muscle, the fractional rates of protein synthesis ( k syn) and degradation ( k deg) were not significantly different between cold and control rats, although k syn was lower (approximately −26%) in cold rats on day 5; consequent to the lower protein mass, the absolute rates of protein synthesis (approximately −21%; P < 0.05) and degradation (approximately −13%; P < 0.1) were lower in cold compared with control rats. In heart, overall, k syn(approximately +12%; P < 0.1) and k deg(approximately +22%; P < 0.05) were higher in cold compared with control rats; consequently, the absolute rates of synthesis (approximately +44%) and degradation (approximately +54%) were higher in cold compared with control rats ( P < 0.05). Plasma triiodothyronine concentration was higher ( P < 0.05) in cold compared with control rats. These data indicate that long-term cold acclimation in skeletal muscle is associated with the establishment of a new homeostasis in protein turnover with decreased protein mass and normal fractional rates of protein turnover. In heart, unlike skeletal muscle, rates of protein turnover did not appear to immediately return to normal as increased rates of protein turnover were observed beyond day 5. These data also indicate that increased rates of protein turnover in skeletal muscle are unlikely to contribute to increased metabolic heat production during cold acclimation.


Author(s):  
Rafael Martinez-Perez ◽  
William Florez-Perdomo ◽  
Lindsey Freeman ◽  
Timothy H. Ung ◽  
A. Samy Youssef

2020 ◽  
Vol 13 (3) ◽  
pp. 1552-1559
Author(s):  
Yuki Muroyama ◽  
Hiroyuki Tamiya ◽  
Goh Tanaka ◽  
Wakae Tanaka ◽  
Alexander C. Huang ◽  
...  

Lung hepatoid adenocarcinoma (HAC) is a rare primary lung carcinoma pathologically characterized by hepatocellular carcinoma-like tumor cells, the majority of which produce alpha-fetoprotein (AFP). The clinical prognosis of lung HAC is generally poor, and effective therapeutic regimens for inoperable or recurrent cases have not been established. Here, we report a case of AFP-producing lung HAC with brain metastasis with long-term disease control, treated with the 5-fluorouracil-derived regimen S-1. The patient was a 66-year-old male admitted to the hospital with alexia. Chest X-ray revealed a massive tumor in the left upper lobe, and a head CT scan revealed a metastasis in the left parietal lobe. The laboratory data showed a remarkably elevated AFP level (97,561 ng/mL). Pathological assessment of the resected brain tumor revealed HAC, which was compatible with the lung biopsies. Together with the absence of other metastatic lesions, a final diagnosis of primary lung HAC, stage IV T4N3M1b, was given. The patient first underwent non-small cell lung cancer chemotherapy regimens (carboplatin and paclitaxel as the first line, and pemetrexed as the second line), but had clinical progression. After third-line oral S-1 (tegafur/gimeracil/oteracil) administration, the serum AFP level significantly dropped and the patient achieved long-term disease control without relapse, surviving more than 19 months after disease presentation. The autopsy result was consistent with the diagnosis of primary lung HAC, and immunohistochemical staining was AFP+, glypican 3+, and spalt-like transcription factor 4+. Here, we report the case of a rare primary lung HAC with apparent disease control on S-1 therapy, together with a literature review.


2013 ◽  
Vol 47 (4) ◽  
pp. 376-381 ◽  
Author(s):  
Mihaela Jurdana ◽  
Maja Cemazar ◽  
Katarina Pegan ◽  
Tomaz Mars

Abstract Background. Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures. Materials and methods. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin - 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death. Results. Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70). Conclusions. Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions.


2009 ◽  
Vol 41 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Anna G. Orr ◽  
Anup Sharma ◽  
Nikolaus B. Binder ◽  
Andrew H. Miller ◽  
Bradley D. Pearce

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