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Local and Circulating Microchimerism Is Associated with Hypersensitivity Pneumonitis

¹ Instituto Nacional de Enfermedades Respiratorias, Mexico, DF, Mexico; ² Instituto Nacional de Pediatría, Mexico, DF, Mexico; ³ Centro Médico Nacional Siglo XXI, Mexico, DF, Mexico; and ⁴ Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico, DF, Mexico

Correspondence and requests for reprints should be addressed to Moisés Selman, M.D., Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, Mexico, DF, Mexico. E-mail: mselmanl{at}yahoo.com.mx

Rationale: Hypersensitivity pneumonitis (HP) is a lymphocytic alveolitis provoked by exposure to a variety of antigens. However, the disease occurs in only a subset of exposed individuals, suggesting that additional factors may be involved. Microchimerism has been implicated in the pathogenesis of autoimmune diseases, especially in those showing increased incidence after childbearing age.

Objectives: To evaluate the presence of circulating and local microchimeric cells in female patients with HP.

Methods: Male microchimerism was examined in 103 patients with HP, 30 with idiopathic pulmonary fibrosis (IPF), and 43 healthy women. All of them had given birth to at least one son, with no twin siblings, blood transfusions, or transplants. Microchimerism was examined by dot blot hybridization (peripheral blood), and by fluorescence in situ hybridization in bronchoalveolar lavage cells and lungs.

Measurements and Main Results: Blood microchimerism was found in 33% of the patients with HP in comparison with 10% in those with IPF (p = 0.019) and 16% in healthy women (p = 0.045). Patients with HP with microchimerism showed a significant reduction of diffusing capacity of carbon monoxide (DL_CO; 53.5 ± 11.9% vs. 65.2 ± 19.7%; p = 0.02) compared with patients with HP without microchimerism. In bronchoalveolar lavage cells, microchimerism was detected in 9 of 14 patients with HP compared with 2 of 10 patients with IPF (p = 0.047). Cell sorting revealed that microchimeric cells were either macrophages or CD4⁺ or CD8⁺ T cells. Male microchimeric cells were also found in the five HP lungs examined by fluorescence in situ hybridization.

Conclusions: Our findings (1) demonstrate that patients with HP exhibit increased frequency of fetal microchimerism, (2) confirm the multilineage capacity of microchimeric cells, and (3) suggest that microchimeric cells may increase the severity of the disease.

Key Words: allergic extrinsic alveolitis • hypersensitivity pneumonitis • microchimerism

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Hypersensitivity pneumonitis occurs in few exposed individuals, suggesting that some promoting factors may be involved. What This Study Adds to the Field Patients with hypersensitivity pneumonitis exhibit an increased frequency of circulating and local microchimerism. Microchimeric cells may increase the severity of hypersensitivity pneumonitis.

 

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