MMP2 Polymorphism Affects Plasma Matrix Metalloproteinase (MMP)-2 Levels, and Correlates with the Decline in Lung Function in Hypersensitivity Pneumonitis Positive to Autoantibodies Patients.

Santiago-Ruiz Santiago-Ruiz,Falfán-Valencia Falfán-Valencia,Montaño Montaño,Mejía Mejía,Buendía-Roldán Buendía-Roldán,Ambrocio-Ortiz Ambrocio-Ortiz,Pérez-Rubio Pérez-Rubio

doi:10.3390/biom9100574

Santiago-Ruiz Santiago-Ruiz, Falfán-Valencia Falfán-Valencia + Show 5 more

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https://doi.org/10.3390/biom9100574

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Abstract

Among hypersensitivity pneumonitis (HP) patients have been identified who develop autoantibodies with and without clinical manifestations of autoimmune disease. Genetic factors involved in this process and the effect of these autoantibodies on the clinical phenotype are unknown. Matrix metalloproteinases (MMPs) have an important role in architecture and pulmonary remodeling. The aim of our study was to identify polymorphisms in the MMP1, MMP2, MMP9 and MMP12 genes associated with susceptibility to HP with the presence of autoantibodies (HPAbs+). Using the dominant model of genetic association, comparisons were made between three groups. For rs7125062 in MMP1 (CC vs. CT+TT), we found an association when comparing groups of patients with healthy controls: HPAbs+ vs. HC (p < 0.001, OR = 10.62, CI 95% = 4.34–25.96); HP vs. HC (p < 0.001, OR = 7.85, 95% CI 95% = 4.54–13.57). This rs11646643 in MMP2 shows a difference in the HPAbs+ group by the dominant genetic model GG vs. GA+AA, (p = 0.001, OR = 8.11, CI 95% = 1.83–35.84). In the linear regression analysis, rs11646643 was associated with a difference in basal forced vital capacity (FVC)/12 months (p = 0.013, β = 0.228, 95% CI95% = 1.97–16.72). We identified single-nucleotide polymorphisms (SNPs) associated with the risk of developing HP, and with the evolution towards the phenotype with the presence of autoantibodies. Also, to the decrease in plasma MMP-2 levels.

Highlights

Hypersensitivity pneumonitis (HP) is a complex disease caused by an exaggerated immune response to the inhalation of a wide variety of organic particles [1]
In this study of genetic association, we show that two single-nucleotide polymorphisms (SNPs) are associated with genetic susceptibility for HP in Mexican Mestizo population
Our findings demonstrate a subgroup of patients with hypersensitivity pneumonitis who develop autoantibodies without meeting the classification criteria for connective tissue disease

Summary

Introduction

Hypersensitivity pneumonitis (HP) is a complex disease caused by an exaggerated immune response to the inhalation of a wide variety of organic particles [1]. ECM proteins have been previously explored as indicators of disease activity, and as potential biomarkers of diagnosis and prognosis in patients with chronic obstructive pulmonary disease (COPD). The existence of hypersensitivity pneumonitis with autoimmune characteristics (HPAF). In a US cohort has been described, determining the prevalence of 15% in the HP patients; in addition, the autoimmunity profile was recognized as an independent predictor of mortality [5]. It is not clear if HPAF patients have different genetic susceptibility characteristics to the non-autoimmunity HP patients. There are no genetic studies on the transforming phenotype of HP patients positive to autoantibodies

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