Lebrikizumab Treatment Reduces Serum Periostin Levels In Asthma Patients With Elevated Baseline Levels Of Periostin
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Periostin
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Periostin is a matrix protein, expressed in fibroblasts and epithelial cells, involved in various biological processes such as cell proliferation, cell invasion and angiogenesis. It is associated with eosinophil migration and tissue infiltration. Serum periostin is considered to be a marker of Th2 inflammation in asthma patients. However, there are no literature data on exhaled breath condensate (EBC) periostin level in children with asthma. The aim of the study was to analyze EBC periostin concentration in children with asthma, as well as to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease. Methods: The non-concentrated EBC and serum periostin concentration was measured by ELISA method in 23 children with mild-to-moderate asthma and 23 healthy controls. Results: EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between EBC (0.04 vs. 0.1ng/mL) periostin in asthmatics and controls were demonstrated. Similarly, there was no difference between serum periostin in these two groups (31.3 vs. 25.2ng/mL, respectively). The comparison between children with Th2 and non-Th2 type of asthma, as well as atopic and non-atopic asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients, but also in controls. Conclusions: In children with mild-to moderate asthma, periostin may be measured not only in serum but also in EBC. A low and not different from control subjects EBC periostin concentration in patients with mild-to-moderate asthma suggest that it cannot be used in this group as an asthma biomarker.
Periostin
Exhaled breath condensate
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Genentech is partnering with the German cancer company Affimed to develop immunotherapies for multiple kinds of solid and blood cancers. Affimed is developing therapies that engage natural killer cells of the innate immune system to help direct them to attack cancer cells. Genentech will pay Affimed $96 million up front and up to $5 billion more in potential payments.
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Periostin, a matricellular protein that modulates cell functions having various pathophysiological roles, has the potential to be a useful biomarker for various diseases. We recently found that periostin forms a complex with IgA in human serum, which may affect the periostin measurement.We investigated (1) whether the formation of the periostin-IgA complex affects the original periostin ELISA system, decreasing the values of serum periostin? (2) bow each domain of periostin affects periostin measurement by the original periostin ELISA system? (3) whether we can establish a novel ELISA system that is not affected by formation of the IgA complex?The periostin value at the reducing condition was significantly higher than that of the non-reducing condition, demonstrating that formation of the IgA complex affects periostin measurement. The monoclonal antibodies (mAbs) for periostin recognizing the EMI and R1 domains immunoprecipitated serum periostin in the reducing condition more than in the non-reducing condition, whereas the mAbs recognizing the R2 or R3 domain immunoprecipitated comparable amounts of serum periostin in the reducing and non-reducing conditions, suggesting the EMI and R1 domains contribute to formation of the complex with IgA. Using SS16A recognizing the R3 domain combined with SS17B recognizing the R4 domain, we established an ELISA system that was able to measure periostin independently of the IgA complex.We have established a novel ELISA system that measures periostin independently of the IgA complex. This system is promising in identifying periostin as a biomarker for various diseases.
Periostin
Matricellular protein
Immunoprecipitation
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Periostin
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Periostin is a matricellular protein belonging to the fasciclin family, playing a role for the pathogenesis of allergic diseases by binding to integrins on cell surfaces. Serum periostin is elevated in various allergic diseases reflecting type 2 inflammation and tissue remodeling so that for allergic diseases, periostin is expected to be a novel biomarker for diagnosis, assessing severity or prognosis, and predicting responsiveness to treatments. We have previously shown that most serum periostin exists in the oligomeric form by intermolecular disulfide bonds.In this study, we examined how periostin forms a complex in serum, whether the periostin complex in serum is functional, and whether the complex formation interferes with reactivity to anti-periostin Abs.We found that periostin formed a complex with IgA1 at a 1:1 ratio. The periostin in the serum complex contained at least five different isoforms. However, IgA was not essential for the oligomeric formation of periostin in mouse serum or in IgA-lacking serum. The periostin-IgA complex in human serum was functional, sustaining the ability to bind to αVβ3 integrin on cell surfaces. Moreover, periostin formed the complex with IgA broadly, which interferes the binding of the Abs recognizing all of the domains except the R4 domain to periostin.Periostin is a novel member of the IgA-associated molecules. These results are of great potential use to understand the pathological roles of periostin in allergic diseases and, from a practical standpoint, to develop diagnostics or therapeutic agents against periostin.
Periostin
Matricellular protein
Pathogenesis
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Periostin
Periosteum
Matricellular protein
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Periostin is an extracellular matrix protein.The mRNA and protein levels of periostin were strongly upregulated after vascular injury,and participate with smooth muscle cell differentiation and migration.Periostin was highly expressed in the myocardium after myocardial infarction and contributed to wound healing and scarring.In addition,periostin was involved in the process of myocarium hypertrophy and interstitial remodeling in heart failure.Periostin play an important role in pathophysiology of cardiovascular remodeling after injury and may be a new target of ischemic heart disease.This article reviewed the relationship between periostin and ischemic heart disease.
Periostin
Pathophysiology
Matricellular protein
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Oral squamous-cell carcinoma (OSCC) is one of the most common types of human cancer. Typically OSCC cells show persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. We previously identified Periostin as the gene demonstrating the highest fold change expression in the invasive clone by comparing the transcriptional profile of parent OSCC cell line and a highly invasive clone. Here, we demonstrated that Periostin overexpression enhanced invasiveness in oral cancer cell lines. To know the role of Periostin in invasion, angiogenesis and metastasis in OSCC cases, we first examined the expression of Periostin mRNA in 31 OSCC cases by RT–PCR and Periostin protein in 74 OSCC cases by immunohistochemistry. Then, we compared the Periostin expression with invasion pattern, metastasis and blood vessel density. Periostin mRNA and protein overexpression were frequently found in OSCC cases and Periostin expression was well correlated with the invasion pattern and metastasis. Moreover, blood vessel density of Periostin-positive cases was higher than those of Periostin-negative cases. Interestingly, recombinant Periostin enhanced capillary formation in vitro in a concentration-dependant manner. In summary, these findings suggest that Periostin may promote invasion and angiogenesis in OSCC, and that Periostin can be a strong marker for prediction of metastasis in oral cancer patients.
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Background: Periostin is a matricellular protein induced in airway epithelia by interleukin-13 (IL13) and a good systemic biomarker for IL13 activity. Lebrikizumab, a humanized monoclonal antibody, binds IL13 and improved lung function in moderate-to-severe asthma patients (pts) with elevated baseline serum periostin in a Phase II study. Aims: To examine the effect of blocking IL13 on systemic periostin levels in pts with uncontrolled asthma, despite inhaled corticosteriods. Methods: Pts (n=218) were randomized to lebrikizumab 250 mg (n=106) or placebo (PB) (n=112) SC every 4 weeks for 6 doses, with 12 weeks follow-up (NCT00930163). Serum periostin was measured at baseline and throughout the study. Pts were classified as periostin-high (≥median) or periostin-low ( Results: PB-corrected reductions in periostin were evident after 1 week of lebrikizumab treatment: 5.4% baseline reduction across all pts and 7.3% baseline reduction in periostin-high pts (p 90%) who were periostin-low at baseline maintained the periostin levels Conclusions: Lebrikizumab reduced serum periostin in periostin-high, but not periostin-low pts, vs placebo. These data suggest that in asthma pts, elevated serum periostin levels are dependent on IL13 activity.
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Matricellular protein
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