Non-invasive IGFBP1, IGFBP2 biomarkers as predictors and outcomes of usual interstitial pneumonia (UIP) therapeutic response

M Habeb,M Zalat,S Embarak,A Fathy

doi:10.1186/s43168-020-00050-x

Abstract

BackgroundUsual interstitial pneumonia (UIP) is a fatal disease that is associated with poor prognosis and survival. Several growth factors such as IGFs (insulin-like growth factors) and IGFBPs (insulin-like growth factor binding proteins) seem to take part to this pathogenesis.Pirfenidone is an immunosuppressant drug that is thought to have anti-inflammatory and anti-fibrotic effects both in vitro and in vivo.ObjectiveTo assess IGFBP1 and IGFBP2 as non-invasive biomarkers for prediction and outcomes of UIP clinical activity and therapeutic response to the anti-fibrotic pirfenidone.ResultsSerum levels of IGFBP1 and IGFBP2 were significantly higher in the UIP group than in the healthy subjects (p ≤ 0.005). After 6 months therapy, UIP patients were divided into 2 groups according to improvement in MRC dyspnea grading into clinically improved and non-improved groups. 6MWT and SPaO2 were significantly improved in the clinically improved group compared to the non-improved one with no differences as regards other parameters (p < 0.0001). Both IGFBP1 and IGFBP2 were significantly decreased in serum while only IGFBP2 was decreased in BAL of all UIP after completing 12 months therapy.ConclusionIGFBP1 and IGFBP2 were increased in active UIP patients and reduced after 12 months anti-fibrosing therapy. IGFBPs may be promising biomarkers and predictors of response to therapy in UIP.

Highlights

Usual interstitial pneumonia (UIP) is a fatal disease that is associated with poor prognosis and survival
Insulin-like growth factor binding protein 1 (IGFBP1) and IGFBP2 were increased in active usual interstitial pneumonia (UIP) patients and reduced after 12 months anti-fibrosing therapy
The UIP patients were divided into 2 groups according to clinical improvement in MRC dyspnea scale into improved or non-improved after completing the Relationship between growth factors and other parameters our study showed a direct relationship between circulating levels of IGFBP2 and Bronchoalveolar fluid (BALF) levels, while we did not find any correlation between IGFBP1 in serum and BALF or between both growth factors and any other biomarkers assessed in our study (Table 4)

Summary

Introduction

Usual interstitial pneumonia (UIP) is a fatal disease that is associated with poor prognosis and survival. Several growth factors such as IGFs (insulin-like growth factors) and IGFBPs (insulin-like growth factor binding proteins) seem to take part to this pathogenesis. Radiological usual interstitial pneumonia (UIP) is characterized on high-. Histopathologic UIP consists of a combination of fibrotic areas with scarring and honeycomb change alternate with areas of less affected or even normal lung parenchyma [3]. The patchy interstitial fibrosis, collagen deposition, and architectural distortion characteristic of the UIP pathologic pattern, evident by surgical pathology or at the macroscale by HRCT, are generally associated with poor prognosis and survival [4]. IGF1 and IGF2 affect local and systemic responses through autocrine, paracrine, and endocrine mechanisms [5]

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