Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy

Kotela, Andrzej; Łęgosz, Paweł; Sarzyńska, Sylwia; Drela, Katarzyna; Pulik, Łukasz; Kaleta, Beata; Kniotek, Monika; Borysowski, Jan; Poniatowski, Łukasz A.; Kotela, Ireneusz

doi:10.1111/1440-1681.13054

Cited by 5 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even with obvious infection lesions in lungs of patients enrolled in this cohort, the levels of CRP were not significantly higher in patients as compared to healthy controls, which is consistent with the result from a previous meta-analysis showing that CRP is only robustly elevated in severe/critical cases. 25 Additionally, it is known that PGRN could competitively bind to tumor necrosis factor receptor 1 (TNFR1) 26 , 27 and TNF-α/TNFR1 is implicated in activating coagulation pathways, 28 it is therefore possible that the high levels of PGRN may block TNF-α mediated inflammation and probably coagulation pathways in COVID-19. Presumably, a lack of competitive blockage of TNF-α-induced coagulatory response due to decreased levels of PGRN in patients with severe/critical COVID-19 may be one of the mechanisms connecting PGRN to the disease severity of COVID-19 as discussed above.…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Yao¹,

Luo²,

Liu³

et al. 2021

JIR

View full text Add to dashboard Cite

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the angiocentric inflammation and angiogenesis, yet the molecules involved in this process remain to be determined. Methods We did a cross-sectional study of a cohort of patients with COVID-19 in Zunyi, China between February 1 and March 30, 2020. Serum concentrations of PGRN were determined by enzyme-linked immunosorbent assay in patients with COVID-19 at hospital admission and at discharge. In parallel, the serum levels of soluble adhesion molecules, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin), and E-selectin (sE-selectin) were assayed by a human adhesion molecule multiplex kit. The association between serum PGRN levels and other laboratory test results was analyzed by Spearman correlation analysis. Results At baseline, the median serum PGRN levels in patients with COVID-19 were 94.8 ng/mL [interquartile range (IQR): 66.6–119.6 ng/mL], which was significantly elevated compared with those in healthy controls (46.3 ng/mL, IQR: 41.8–55.6 ng/mL). Moreover, the median serum sVCAM-1 levels were significantly higher in COVID-19 patients (1396.0 ng/mL, IQR: 1019.1–1774.8 ng/mL) than those in healthy controls (612.4 ng/mL, IQR: 466.4–689.3 ng/mL). However, the levels of sICAM-1, sP-selectin, and sE-selectin were not significantly elevated in patients with COVID-19 when compared to healthy controls. Further analysis showed that serum PGRN levels were significantly positively associated with sVCAM-1 (r= 0.675, P = 0.008) and inversely with sICAM-1 (r= −0.609, P = 0.021) and aspartate aminotransferase levels (r= −0.560, P = 0.037) in patients with COVID-19 at hospital admission. In COVID-19 patients, serum PGRN and sVCAM-1 levels fell significantly after successful treatment. Conclusion The present study demonstrates elevated serum PGRN and sVCAM-1 levels in patients with COVID-19, which may provide clues as to the mechanisms underlying the pathogenesis of COVID-19. Further studies are warranted to evaluate the potential of PGRN and sVCAM-1 as biomarkers and investigate their role in the pathogenesis of COVID-19.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Yao¹,

Luo²,

Liu³

et al. 2021

JIR

View full text Add to dashboard Cite

show abstract

“…(b) The cause of the increasing serum PGRN levels observed in OA patients may not be due to the disease process. Kotela et al 20 have found no significant correlation between serum PGRN levels and clinical characteristics including Knee Society Score (KSS)-knee, KSS-function, and KSS-total in OA patients.…”

Section: Discussionmentioning

confidence: 99%

Serum progranulin to TNF-α ratio in patients with gonarthrosis

Yıldız

Boy

2021

AOTT

View full text Add to dashboard Cite

Objective Progranulin (PGRN) is a growth factor that has antiinflammatory, immunosuppressive, and chondroprotective effects. It blocks Tumor Necrosis Factor- α (TNF- α ) signal pathway by binding its receptor. Recently, it has been claimed that PGRN may be overexpressed in patients with Osteoarthritis (OA). However, these patients tend to be obese and obesity also may be one of the factors that affect PGRN levels. The aim of this study was to compare the PGRN levels of patients with Knee OA (KOA) with that of healthy controls by eliminating the effect of obesity and to evaluate PGRN-to-Tumor Necrosis Factor- α (TNF- α ) ratio in KOA, both of which were investigated first in literature by this study. Methods A total of 80 individuals (40 patients with KOA and 40 healthy controls) were included in this study. The patients and controls were divided into two groups according to their Body Mass Indexes (BMI): nonobese (BMI between 18.5 and 24.9) and obese (BMI of 30 or higher). Each of the groups included 20 subjects and had an equal number of men and women. Blood samples were obtained from all participants, and the serum PGRN and TNF- α levels were measured using commercial ELISA kits. Results There was no difference among groups in terms of age ( P = 0.416) and gender distribution. There was no statistical difference among study groups with regard to serum PGRN levels. Serum TNF- α levels were significantly higher in obese controls ( P < 0.001) and nonobese patients ( P = 0.003) compared to that of nonobese healthy controls. Correspondingly, serum PGRN-to-TNF- α ratio was considerably lower in obese controls ( P < 0.001) and nonobese patients ( P < 0.001) by comparison with that of nonobese healthy controls. Conclusion We determined that both obesity and KOA increased serum TNF- α levels and concordantly decreased serum PGRN-to-TNF- α ratio. The results of the study suggest that the activation of the PGRN pathway and/or the inhibition of the TNF α pathway may be essential in terms of the reestablishment of the disrupted inflammatory balance in patients with KOA. Level of Evidence Level III, Diagnostic study

show abstract

“…Furthermore, a recent study showed that similarly to OA and RA, patients with HA exhibit increased levels of progranulin (PGRN), a molecule known for its protective role toward TNFα catabolic effects (Kotela et al, 2018). This evidence could open future hypotheses on its potential role as a serum-maker for monitoring disease activity.…”

Section: Tnfαmentioning

confidence: 98%

Pathophysiological Role of Synovitis in Hemophilic Arthropathy Development: A Two-Hit Hypothesis

et al. 2020

View full text Add to dashboard Cite

Despite an increasing access to prophylaxis with clotting factor concentrates, arthropathy still represents the main chronic complication of hemophilia. Whereas previous studies described hemophilic arthropathy (HA) as a degenerative arthropathy, somehow resembling osteoarthritis (OA), most recent evidence suggests that complex inflammatory and immunologic mechanisms are also involved in the pathophysiology of HA. In the present review, we described available data on major mechanisms leading to arthropathic changes in patients with hemophilia, with a specific focus on the role of synovium. The presence of hemosiderin in the joint space induces synovium proliferation, thus leading to formation of several lytic enzymes determining chondrocytes apoptosis and proteoglycans levels reduction. This leads to a direct joint "chemical" damage representing early damages in the pathogenesis of HA (first hit). In parallel, synovial membrane and synovial endothelial cells become a dynamic reservoir of inflammatory cells and mediators, and propagate the inflammatory response (second hit), switching the process from a chemical damage to an inflammatory damage. Overall, consistent data pointed out synovitis as the keystone in HA pathophysiology. This opens novel potential therapeutic targets in this clinical setting.

show abstract

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy

Cited by 5 publications

References 45 publications

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Serum progranulin to TNF-α ratio in patients with gonarthrosis

Pathophysiological Role of Synovitis in Hemophilic Arthropathy Development: A Two-Hit Hypothesis

Contact Info

Product

Resources

About