MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility

• Published in: Human genetics Vol. 125; no. 5-6; pp. 639 - 648
• Main Authors: Aquino-Galvez, Arnoldo, Pérez-Rodríguez, Martha, Camarena, Ángel, Falfan-Valencia, Ramces, Ruiz, Víctor, Montaño, Martha, Barrera, Lourdes, Sada-Ovalle, Isabel, Ramírez, Remedios, Granados, Julio, Pardo, Annie, Selman, Moisés
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.06.2009; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Analysis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biopsy; Case-Control Studies; Cell receptors; Cell structures and functions; Cells, Cultured; Classical genetics, quantitative genetics, hybrids; Development and progression; Enzyme-linked immunosorbent assay; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Frequency; Gene Function; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Histocompatibility Antigens Class I - blood; Histocompatibility Antigens Class I - genetics; HLA-B Antigens - genetics; Human; Human Genetics; Humans; Idiopathic Pulmonary Fibrosis - genetics; Killer cells; Killer Cells, Natural - metabolism; Lung - metabolism; Lung diseases; Lungs; Lymphocytes; Male; Medical sciences; Metabolic Diseases; Middle Aged; Miscellaneous; Molecular and cellular biology; Molecular Medicine; NK Cell Lectin-Like Receptor Subfamily K - genetics; NK Cell Lectin-Like Receptor Subfamily K - metabolism; Original Investigation; Pneumology; Polymorphism, Genetic; Proteins; Pulmonary fibrosis; Respiratory system : syndromes and miscellaneous diseases; Risk factors; Sequence Analysis, DNA; Society; T cells; T-Lymphocyte Subsets - metabolism; Mexico; Idiopathic Pulmonary Fibrosis; Major Histocompatibility Complex; Hypersensitivity Pneumonitis; Idiopathic Pulmonary Fibrosis Patient; Alveolar Epithelial Cell; Lung disease; Pulmonary fibrosis; Respiratory disease; Idiopathic; MICA ligand; Genetics; Polymorphism; Biological receptor
• ISSN: 0340-6717; 1432-1203; 1432-1203
• DOI: 10.1007/s00439-009-0666-1

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disorder of unknown etiology. IPF is likely the result of complex interrelationships between environmental and host factors, although the genetic risk factors are presently uncertain. Because we have found that some MHC polymorphisms confer susceptibility to IPF, in the present study we aimed to evaluate the role of the MHC class I chain-related gene A (MICA) in the risk of developing the disease. MICA molecular typing was done by reference strand mediated conformation analysis in a cohort of 80 IPF patients and 201 controls. In addition, the lung cellular source of the protein was examined by immunohistochemistry, the expression of the MICA receptor NKG2D in lung cells by flow cytometry and soluble MICA by ELISA. A significant increase of MICA*001 was observed in the IPF cohort (OR = 2.91, 95% CI = 1.04-8.25; pC = 0.03). Likewise, the frequency of the MICA*001/*00201 genotype was significantly increased in patients with IPF compared with the healthy controls (OR = 4.72, 95% CI = 1.15-22.51; pC = 0.01). Strong immunoreactive MICA staining was localized in alveolar epithelial cells and fibroblasts from IPF lungs while control lungs were negative. Soluble MICA was detected in 35% of IPF patients compared with 12% of control subjects (P = 0.0007). The expression of NKG2D was significantly decreased in γδ T cells and natural killer cells obtained from IPF lungs. These findings indicate that MICA polymorphisms and abnormal expression of the MICA receptor NKG2D might contribute to IPF susceptibility.