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

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Abstract

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.

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Acknowledgments

This study was supported by Universidad Nacional Autónoma de México, Grant SDI.PTID.05.6.

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Authors and Affiliations

  1. Instituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Tlalpan 4502, CP 14080, Mexico DF, Mexico

    Arnoldo Aquino-Galvez, Ángel Camarena, Ramces Falfan-Valencia, Víctor Ruiz, Martha Montaño, Lourdes Barrera, Isabel Sada-Ovalle & Moisés Selman

  2. Unidad de Investigación Médica en Inmunología, CMN S-XXI Instituto Mexicano del Seguro Social, Mexico DF, Mexico

    Martha Pérez-Rodríguez

  3. Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico DF, Mexico

    Remedios Ramírez & Annie Pardo

  4. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico DF, Mexico

    Julio Granados

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  1. Arnoldo Aquino-Galvez
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  2. Martha Pérez-Rodríguez
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  3. Ángel Camarena
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  11. Annie Pardo
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  12. Moisés Selman
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Correspondence to Moisés Selman.

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This work was submitted in partial fulfillment of the requirements to obtain the PhD degree for AAG at Biological Sciences, UNAM.

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Aquino-Galvez, A., Pérez-Rodríguez, M., Camarena, Á. et al. MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility. Hum Genet 125, 639–648 (2009). https://doi.org/10.1007/s00439-009-0666-1

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