Increased production of acute-phase proteins corresponds to the peak parasitaemia of primary malaria infection

Abstract Background Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. Methods We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. Results In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. Conclusions These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.

Download Full-text

Effects of Stocking and Transport Conditions on Physicochemical Properties of Meat and Acute-Phase Proteins in Cattle

Foods ◽

10.3390/foods10020252 ◽

2021 ◽

Vol 10 (2) ◽

pp. 252

Author(s):

Ahmed A. Abubakar ◽

Idrus Zulkifli ◽

Yong M. Goh ◽

Ubedullah Kaka ◽

Azad B. Sabow ◽

...

Keyword(s):

Physicochemical Properties ◽

Acute Phase ◽

Acute Phase Proteins ◽

Stocking Density ◽

Road Transport ◽

Long Distance ◽

Amyloid A ◽

Tropical Conditions ◽

Meat Samples ◽

Water Holding

This study’s objective was to evaluate the effects of distance and stocking density on physicochemical properties and oxidative stability of meat and acute-phase proteins in Brahman crossbred cattle transported by road under hot and humid tropical conditions. Sixty Brahman crossbred heifers were subjected to road transport from a cattle feedlot farm located in Universiti Putra Malaysia (UPM), Serdang, to a commercial ruminant abattoir in Shah Alam, Selangor. Animals were assigned to long and short distances and high, medium, and low stocking densities. The results revealed that the intensity of response significantly increased in meat samples from animals subjected to long-distance transportation and higher stocking density. Alpha-1-acid glycoprotein and serum amyloid-A values increased considerably and were different from the baseline values recorded at preload. In conclusion, the current results revealed that the color, pH, shear force values, water holding capacity (WHC), glycogen level, and malondilaldehyde assay (MDA) concentrations in meat and acute-phase proteins (APP) were affected by both distances and stocking densities, as evidenced by the significant changes recorded from the parameters above.

Download Full-text

OP0229 GUSELKUMAB INDUCES SUSTAINED REDUCTION IN ACUTE PHASE PROTEINS AND TH17 EFFECTOR CYTOKINES IN ACTIVE PSORIATIC ARTHRITIS IN TWO PHASE-3 CLINICAL TRIALS (DISCOVER-1 AND DISCOVER-2)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1240 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 144-145

Author(s):

S. Siebert ◽

I. Mcinnes ◽

M. J. Loza ◽

K. MA ◽

K. Leander ◽

...

Keyword(s):

Acute Phase ◽

Acute Phase Proteins ◽

Geometric Mean ◽

Tnf Inhibitor ◽

Healthy Controls ◽

Phase 3 ◽

Two Phase ◽

Protein Levels ◽

Disease Characteristics ◽

Effector Cytokines

Background:Guselkumab (GUS), an IL-23 inhibitor monoclonal antibody (Mab) that specifically binds to the IL-23p19 subunit, demonstrated efficacy compared to placebo (PBO) in reducing skin and musculoskeletal signs and symptoms in patients (pts) with active psoriatic arthritis (PsA) in two phase-3 studies, DISCOVER 1 & 2.1,2Previous results from a GUS PsA Phase-2 trial3and Ustekinumab (UST, anti-IL12/23p40 MAb) PsA Phase-3 trials (PSUMMIT 1 & 2)4showed associations of baseline IL-17A, IL-17F, and CRP with baseline disease characteristics, and associations of GUS-induced cytokine reductions with clinical responses.Objectives:To investigate plausible cytokine expression in PsA and alterations after exposure to GUS therapy.Methods:In DISCOVER 1 & 2, pts were treated with GUS 100 mg at Wk 0, 4, then every 8Wks (q8w); GUS 100mg q4w; or matching PBO. 21 serum biomarkers were measured in a random subset of 300 PsA pts from the DISCOVER program at Weeks (Wks) 0, 4, & 24 and in 34 healthy controls matched for age, sex, and ethnicity. Serum proteins measured were acute phase reactants CRP & SAA (Meso Scale Discovery (MSD) Platform) and inflammatory cytokines/chemokines: Th17 effector cytokines IL-17A, IL-17F, & IL-22 (Single Molecule Counting Erenna® Immunoassay Platform) and soluble ICAM-1, soluble VCAM-1, IL-6, CXCL-8, IL-10, IL-13, IL-12p70, CCL22, IFN-γ, CCL2, CCL4, TNFα, IL-1β, IL-2, IL-4 (MSD), & YKL-40 (Quantikine Immunoassay). Serum IL-17A, IL-17B, & CRP measured in the Phase-3 PSUMMIT trials of UST for PsA4were included for comparison with GUS.Results:At baseline, serum levels of acute phase proteins CRP, SAA, & IL-6, and Th17-effector cytokines IL-17A & IL-17F were elevated in pts with PsA compared with healthy controls (p<0.05, geometric mean ≥ 40% higher, FIG 1). There was no significant dysregulation in the other cytokines measured in PsA pts compared to healthy controls. Baseline IL-17A, IL-17F, IL-22, & CCL22 were significantly associated with baseline psoriasis disease activity (Body Surface Area & Psoriatic Area and Severity Index, Spearman Signed Rank p<0.05, r>0.25). Baseline CRP, SAA, IL-6, & YKL40 were significantly associated with baseline joint disease (Disease Activity Score 28-CRP, Spearman p<0.05, r>0.25). Baseline SAA, IL-6, IL-17A, & IL-17F were higher in pts with prior TNF inhibitor exposure than without (p<0.05, geometric mean ≥ 40% higher), although pts with PsA both with and without prior TNF inhibitor had higher levels than the healthy control set.GUS treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F, & IL-22 that were significantly greater than PBO as early as Week 4 (FIG 1). These protein levels continued to decrease through Wk 24 in GUS-treated pts with both dosing regimens (p<0.05, geometric mean decrease from baseline ≥ 33%). Further, Wk 24 IL-17A & IL-17F levels for pts treated with either dose of GUS were not significantly different from healthy controls, suggesting a normalization of peripheral effector cytokines associated with the IL-23/Th17 axis following treatment with GUS. Effects on IL-17A/IL-17F were greater in GUS treated pts than UST treated pts, while CRP levels were similar in both programs (FIG 2).Conclusion:Comprising a strong pharmacodynamic effect, GUS treatment reduced serum protein levels of acute phase and Th17-effector cytokines (whose elevations at baseline were associated with PsA disease characteristics) and achieved comparable levels to those in healthy controls. In pts with PsA, reductions of IL-17A and IL-17F by GUS were of greater magnitude than those by UST.References:[1]Deodhar et al. ACR 2019, abs #807. Arth Rheumatol. 2019;71 S10: 1386[2]Mease et al. ACR 2019, abs #L13. Arth Rheumatol. 2019;71 S10:5247[3]Siebert et al. EULAR 2019, abs #479. Ann Rheum Dis. 2019;78 S2:293[4]Siebert et al. Arth Rheumatol. 2019;71:1660Acknowledgments:NoneDisclosure of Interests:Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Matthew J Loza Employee of: Janssen Research & Development, LLC, Keying Ma Employee of: Janssen Research & Development, LLC, Karen Leander, Employee of: Janssen Research & Development, LLC, Vani Lakshminarayanan Employee of: Janssen Research & Development, LLC, Carol Franks Employee of: Janssen Research & Development, LLC, Philip Cooper Employee of: Janssen Research & Development, LLC, Kristen Sweet Employee of: Janssen Research & Development, LLC

Download Full-text

FUNCTIONS OF ACUTE PHASE PROTEINS IN THE INFLAMMATORY RESPONSE

Proceedings of the Second Symposium Lyon, France, June 27–30, 1983 ◽

10.1515/9783112328262-012 ◽

1984 ◽

pp. 89-98

Keyword(s):

Inflammatory Response ◽

Acute Phase ◽

Acute Phase Proteins

Download Full-text

Functions of Acute Phase Proteins in the Inflammatory Response

Proceedings of the Second Symposium Lyon, France, June 27–30, 1983 ◽

10.1515/9783112314883-012 ◽

1984 ◽

pp. 89-98

Keyword(s):

Inflammatory Response ◽

Acute Phase ◽

Acute Phase Proteins

Download Full-text

Liver dysfunction in COVID-19: a useful prognostic marker of severe disease?

Frontline Gastroenterology ◽

10.1136/flgastro-2020-101689 ◽

2020 ◽

pp. flgastro-2020-101689

Author(s):

James Lok ◽

Markus Gess

Keyword(s):

Liver Function ◽

Acute Phase ◽

Liver Dysfunction ◽

Acute Phase Proteins ◽

Severe Disease ◽

Ventilatory Support ◽

Length Of Hospital Stay ◽

Abnormal Liver Function ◽

Adverse Outcomes ◽

High Dependency

BackgroundCOVID-19 is a global pandemic caused by the novel coronavirus SARS-CoV-2. Risk factors and prognostic markers of severe disease remain to be fully determined, although some studies have suggested a correlation between abnormal liver function and adverse outcomes. Further studies are needed to investigate this further.MethodsThis retrospective study enrolled patients with a confirmed diagnosis of COVID-19 who were admitted to Kingston Hospital in the UK. Data collected included age, sex, ethnicity, comorbidity profile, biochemical markers of liver function and the acute phase response, and overall outcome.ResultsBetween 16 March 2020 and 30 April 2020, a total of 343 patients were admitted to the acute medical team at Kingston Hospital. Excluding those with a history of liver disease, 299 patients had liver function tests performed with abnormalities demonstrated in 44.8% of individuals. Derangement of liver function was associated with greater need for ventilatory support (p<0.001), admission to high dependency unit or intensive care (p<0.001) and increased length of hospital stay (p<0.001). Of note, liver dysfunction was more common in those of non-white ethnicity (p=0.007) and correlated with higher levels of C reactive protein (p=0.01) and ferritin (p<0.001).ConclusionAbnormal liver function is associated with a negative outcome among those hospitalised with COVID-19. The cause for this association is unclear, but correlation between abnormal liver function and higher serum levels of acute phase proteins suggest that dysregulation of the immune system in response to SARS-CoV-2 may be contributory.

Download Full-text