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Interstitial Lung Disease with Multiple Microgranulomas in Chronic Granulomatous Disease

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Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Background

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. CGD patients also suffer from immune regulatory disorders, such as CGD-associated bowel inflammation with granuloma, which could be caused by excessive inflammation without demonstrable infection.

Purpose

We investigated the clinical manifestation of interstitial lung disease (ILD) resulting from excessive inflammation in X-linked CGD patients.

Methods

Pulmonary CT images and testing of serum KL-6 levels were performed to assess ILD in the patients. For this study, patients with pulmonary lesions due to demonstrable infections were excluded from among ILD patients.

Results

Among 33 CGD patients, four developed ILD; they had increased reticulo-nodular opacities on CT images and elevated serum KL-6 levels. Histopathological examinations revealed multiple homogeneous microgranulomas in the lesions of inflammatory cell infiltration. Mononuclear cells obtained from their pulmonary lesions produced higher amounts of inflammatory cytokines than the peripheral blood mononuclear cells of CGD patients, suggesting that the only infiltrating cells in the pulmonary lesions were activated and produced large amounts of inflammatory cytokines in ILD patients. Interestingly, an anti-inflammatory drug, such as a corticosteroid or thalidomide, but not anti-bacterial or anti-fungal drugs, improved CT image findings and reduced their KL-6 levels.

Conclusions

CGD patients’ daily exposures to inhaled antigens may induce excessive reactions with the production of inflammatory cytokines leading to the development of ILD with multiple microgranulomas, which could be due to an inadequate production of reactive oxygen species in CGD.

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Acknowledgments

We are grateful to the CGD patients and blood donors for their participation in this study. The manuscript was proofread and edited by Dr. Julian Tang of the Department of Clinical Research Education, National Center for Child Health and Development. This study was supported by a Grant from the National Center for Child Health and Development.

Conflict of Interest

The authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Toshinao Kawai, Nobuyuki Watanabe, Midori Yokoyama, Yumiko Nakazawa, Fumihiro Goto, Toru Uchiyama & Masafumi Onodera

  2. Division of Pulmonology, National Center for Child Health and Development, Tokyo, Japan

    Masataka Higuchi

  3. Department of Pediatrics, National Center for Child Health and Development, Tokyo, Japan

    Takanobu Maekawa

  4. Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan

    Eiichiro Tamura

  5. Division of General Thoracic Surgery, National Center for Global Health and Medicine Japan, Tokyo, Japan

    Satoshi Nagasaka

  6. Division of Respiratory Medicine, National Center for Global Health and Medicine Japan, Tokyo, Japan

    Masayuki Hojo

Authors
  1. Toshinao Kawai
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  2. Nobuyuki Watanabe
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  3. Midori Yokoyama
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  4. Yumiko Nakazawa
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  12. Masafumi Onodera
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Corresponding author

Correspondence to Toshinao Kawai.

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Kawai, T., Watanabe, N., Yokoyama, M. et al. Interstitial Lung Disease with Multiple Microgranulomas in Chronic Granulomatous Disease. J Clin Immunol 34, 933–940 (2014). https://doi.org/10.1007/s10875-014-0089-1

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  • DOI: https://doi.org/10.1007/s10875-014-0089-1

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