Circulating MMP-12 as Potential Biomarker in Evaluating Disease Severity and Efficacy of Sublingual Immunotherapy in Allergic Rhinitis

Zhou, Yandan; Xu, Min; Gǒng, Wànkuí; Kang, Xiaoming; Guo, Renzhong; Wen, Jinyu; Zhou, Dinggang; Wang, Manjing; Shi, Dazhi; Jing, Qiancheng

doi:10.1155/2022/3378035

Cited by 9 publications

(11 citation statements)

References 41 publications

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“…All three of these genes have known associations with allergen‐activated type 2 inflammation, including eosinophils, type 2 cytokines, and T helper 2 (Th2) cells. Variable expression of CLC and circulating levels of MMP‐12 have been suggested as potential biomarkers of AR disease and AR disease severity, 42–44 further emphasizing the biological relevance of our defined AR signatures.…”

Section: Resultsmentioning

confidence: 83%

Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy

Wipperman,

Gayvert,

Atanasio

et al. 2024

Allergy

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BackgroundNasal epithelial cells are important regulators of barrier function and immune signaling; however, in allergic rhinitis (AR) these functions can be disrupted by inflammatory mediators. We aimed to better discern AR disease mechanisms using transcriptome data from nasal brushing samples from individuals with and without AR.MethodsData were drawn from a feasibility study of individuals with and without AR to Timothy grass and from a clinical trial evaluating 16 weeks of treatment with the following: dupilumab, a monoclonal antibody that binds interleukin (IL)‐4Rα and inhibits type 2 inflammation by blocking signaling of both IL‐4/IL‐13; subcutaneous immunotherapy with Timothy grass (SCIT), which inhibits allergic responses through pleiotropic effects; SCIT + dupilumab; or placebo. Using nasal brushing samples from these studies, we defined distinct gene signatures in nasal tissue of AR disease and after nasal allergen challenge (NAC) and assessed how these signatures were modulated by study drug(s).ResultsTreatment with dupilumab (normalized enrichment score [NES] = −1.73, p = .002) or SCIT + dupilumab (NES = −2.55, p < .001), but not SCIT alone (NES = +1.16, p = .107), significantly repressed the AR disease signature. Dupilumab (NES = −2.55, p < .001), SCIT (NES = −2.99, p < .001), and SCIT + dupilumab (NES = −3.15, p < .001) all repressed the NAC gene signature.ConclusionThese results demonstrate type 2 inflammation is an important contributor to the pathophysiology of AR disease and that inhibition of the type 2 pathway with dupilumab may normalize nasal tissue gene expression.

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Section: Resultsmentioning

confidence: 83%

Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy

Wipperman,

Gayvert,

Atanasio

et al. 2024

Allergy

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“… 6 The diagnostic criteria for MAR and MSAR were performed based on total nasal symptom score (TNSS) as our previous publication described, TNSS≤4 was defined as MAR, and TNSS >4 was regarded as MSAR. 17 The exclusion criteria for this study were performed as our previous study: 18 the presence of concomitant immune or inflammatory diseases, severe renal, hepatic, or cardiac dysfunction, age below 18 years, pregnancy or potential pregnancy, and history of immunotherapy or systemic steroid or anti-allergy drug use within 1 month before enrollment. HCs were excluded if they were currently undergoing immunotherapy or receiving systemic steroid or anti-allergy treatment and had severe cardiac or renal dysfunction.…”

Section: Methodsmentioning

confidence: 99%

“…The standardized Der f drops, supplied by Wolwo Pharma Biotechnology Company (Zhejiang, China), were self-administered by the AR patients as previously described. 18 The initial administration was supervised by a physician. Any adverse reactions that occurred during the therapy period were documented.…”

Section: Methodsmentioning

confidence: 99%

Soluble TAM Receptor Tyrosine Kinases Correlate with Disease Severity and Predict the Early Responsiveness of Sublingual Immunotherapy in Allergic Rhinitis

Zhou,

Feng,

Wen

et al. 2023

JIR

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Background Allergic rhinitis (AR) is a common allergic disease, and SLIT has shown effectiveness as a treatment method. This study focuses on the evaluation of serum TAM receptor tyrosine kinases (TYRO3, AXL, and MER) levels as potential indicators of disease severity and predictive markers for sublingual immunotherapy (SLIT) responsiveness in AR patients. Methods A total of 160 AR subjects, including 40 mild AR (MAR) and 120 moderate-severe AR (MSAR) patients, and 40 healthy controls (HC) were recruited. Serum concentrations of TYRO3, AXL, and MER were measured and their relationships with disease severity were examined. In the MSAR group, 102 patients underwent SLIT, and the early efficacy was evaluated. The correlations between the baseline serum concentrations of TYRO3, AXL, and MER and the early responsiveness of SLIT were analyzed. Results Serum concentrations of TYRO3, AXL, and MER were significantly reduced in AR patients, particularly in those MSAR subjects. Correlation analysis results indicated that serum TYRO3 and MER levels were negatively correlated with the visual analog scale (VAS) and the total nasal symptom score (TNSS). After one year of follow-up, 80 AR patients completed the treatment and were divided into effective and ineffective groups. Serum baseline levels of TYRO3 and MER were found to be lower in the effective group compared to the ineffective group. Additionally, there was a significant increase in serum TYRO3 and MER levels compared to baseline levels. Receiver operating characteristic (ROC) analysis revealed that circulating TYRO3 and MER had potential values for reflecting AR severity and predicting early SLIT responsiveness. Conclusion Serum TYRO3 and MER concentrations were decreased in AR patients and negatively associated with disease severity. Circulating TYRO3 and MER seem to be promising indicators for monitoring the efficacy of SLIT in AR patients.

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“…Matrix metalloproteinase-12 (MMP-12) can be induced by M2 macrophages, and promote the proliferation of Th2 cells, and secretion of IL-4 and IL-13 [ 143 ]. Zhou et al [ 144 ] found that circulating serum MRGPRX2 and MMP-12 levels were lower in the AR SLIT-treated group and useful for evaluating the disease severity.…”

Section: Predictive Biomarkers For Ait Outcomes In Allergic Diseasesmentioning

confidence: 99%

Mechanisms and biomarkers of successful allergen-specific immunotherapy

López

Imam

Satitsuksanoa

et al. 2022

Asia Pacific Allergy

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Allergen-specific immunotherapy (AIT) is considered the only curative treatment for allergic diseases mediated by immunoglobulin E (IgE). Currently, the route of administration depends both on the different types of causal allergens and on its effectiveness and safety profile. Several studies have reported the mechanisms and changes in humoral and cellular response underlying AIT; however, the full picture remains unknown. Knowledge of who can benefit from this type of treatment is urgently needed due to the patient safety risks and costs of AIT. In vivo or in vitro biomarkers have become a strategy to predict clinical outcomes in precision medicine. There are currently no standardized biomarkers that allow determining successful responses to AIT, however, some studies have found differences between responders and nonresponders. In addition, different candidates have been postulated that may have the potential to become biomarkers. In this review, we aim to summarize the findings to date related to biomarkers in different IgE-mediated allergic diseases (respiratory, food, and venom allergy) with the potential to define who will benefit from AIT.

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Circulating MMP-12 as Potential Biomarker in Evaluating Disease Severity and Efficacy of Sublingual Immunotherapy in Allergic Rhinitis

Cited by 9 publications

References 41 publications

Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy

Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy

Soluble TAM Receptor Tyrosine Kinases Correlate with Disease Severity and Predict the Early Responsiveness of Sublingual Immunotherapy in Allergic Rhinitis

Mechanisms and biomarkers of successful allergen-specific immunotherapy

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