Detection of <i>Cutibacterium acnes</i> in granulomas of patients with either hypersensitivity pneumonitis or vasculitis reveals that its presence is not unique for sarcoidosis

Beijer, Els; Seldenrijk, Kees A.; Meek, Bob; Damen, J.J.M.; Quanjel, Marian J.R.; Grutters, Jan C.; Veltkamp, Marcel

doi:10.1183/23120541.00930-2020

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Interestingly, in light of the potential of C. acnes to skew an immune response towards a more Th-1 response they categorized HP patients into a group where C. acnes was present in the granulomas and a group without the presence of C. acnes in the granulomas. When comparing the amount of lymphocytosis in BAL fluid between both groups it was found that the presence of C. acnes in the granulomas of patients with HP was associated with a significantly higher amount of lymphocytes in BAL fluid (Figure 3), further supporting the hypothesis that the role of C. acnes could be mitogenic in different granulomatous pulmonary disorders [114].…”

Section: A Possible Role Of C Acnes As a Mitogen In Sarcoidosissupporting

confidence: 54%

The Role of Cutibacterium acnes in Sarcoidosis: From Antigen to Treatable Trait?

Kraaijvanger

Veltkamp

2022

Microorganisms

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Cutibacterium acnes (C. acnes, formerly Propionibacterium acnes) is considered to be a non-pathogenic resident of the human skin, as well as mucosal surfaces. However, it also has been demonstrated that C. acnes plays a pathogenic role in diseases such as acne vulgaris or implant infections after orthopedic surgery. Besides a role in infectious disease, this bacterium also seems to harbor immunomodulatory effects demonstrated by studies using C. acnes to enhance anti-tumor activity in various cancers or vaccination response. Sarcoidosis is a systemic inflammatory disorder of unknown causes. Cultures of C. acnes in biopsy samples of sarcoidosis patients, its presence in BAL fluid, tissue samples as well as antibodies against this bacterium found in serum of patients with sarcoidosis suggest an etiological role in this disease. In this review we address the antigenic as well as immunomodulatory potential of C. acnes with a focus on sarcoidosis. Furthermore, a potential role for antibiotic treatment in patients with sarcoidosis will be explored.

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Section: A Possible Role Of C Acnes As a Mitogen In Sarcoidosissupporting

confidence: 54%

The Role of Cutibacterium acnes in Sarcoidosis: From Antigen to Treatable Trait?

Kraaijvanger

Veltkamp

2022

Microorganisms

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“…Unstained tissue blocks of two study cohorts previously studied at the St. Antonius Hospital (Nieuwegein, The Netherlands) were requested; one cohort contained 76 sarcoidosis patients [ 12 ] and the other cohort consisted of 48 patients with other granulomatous disorders [ 13 ]. The diagnosis of sarcoidosis had been established according to the criteria of the American Thoracic Society/European Respiratory society [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Activation of Downstream mTORC1 Target Ribosomal Protein S6 Kinase (S6K) Can Be Found in a Subgroup of Dutch Patients with Granulomatous Pulmonary Disease

Kraaijvanger

Seldenrijk

Beijer

et al. 2021

Cells

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Mechanistic target of rapamycin complex 1 (mTORC1) has been linked to different diseases. The mTORC1 signaling pathway is suggested to play a role in the granuloma formation of sarcoidosis. Recent studies demonstrated conflicting data on mTORC1 activation in patients with sarcoidosis by measuring activation of its downstream target S6 kinase (S6K) with either 33% or 100% of patients. Therefore, the aim of our study was to reevaluate the percentage of S6K activation in sarcoidosis patients in a Dutch cohort. To investigate whether this activation is specific for sarcoid granulomas, we also included Dutch patients with other granulomatous diseases of the lung. The activation of the S6K signaling pathway was evaluated by immunohistochemical staining of its downstream effector phospho-S6 in tissue sections. Active S6K signaling was detected in 32 (43%) of the sarcoidosis patients. Twelve (31%) of the patients with another granulomatous disorder also showed activated S6K signaling, demonstrating that the mTORC1 pathway may be activated in a range for different granulomatous diseases (p = 0.628). Activation of S6K can only be found in a subgroup of patients with sarcoidosis, as well as in patients with other granulomatous pulmonary diseases, such as hypersensitivity pneumonitis or vasculitis. No association between different clinical phenotypes and S6K activation can be found in sarcoidosis.

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“…In the present study, P. acnes was found in interstitial and alveolar macrophages in 88% and 35% lung tissues, respectively, from patients with other granulomatous diseases, including HP and GPA, although no P. acnes was detected in these non-sarcoid granulomas. Recently, Beijer et al [ 27 ] reported that P. acnes was found in the lung tissue of 57% HP patients and 33% GPA patients and observed inside granulomas of 26% HP patients and 11% GPA patients, concluding that P. acnes may be involved in the disease pathogenesis of those granulomatous diseases in a mitogenic way. The difference in the detection frequency of P. acnes in HP or GPA granulomas, however, may be caused by different histologic evaluation of granuloma.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody

et al. 2021

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Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody.

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Detection of Cutibacterium acnes in granulomas of patients with either hypersensitivity pneumonitis or vasculitis reveals that its presence is not unique for sarcoidosis

Cited by 7 publications

References 14 publications

The Role of Cutibacterium acnes in Sarcoidosis: From Antigen to Treatable Trait?

The Role of Cutibacterium acnes in Sarcoidosis: From Antigen to Treatable Trait?

Activation of Downstream mTORC1 Target Ribosomal Protein S6 Kinase (S6K) Can Be Found in a Subgroup of Dutch Patients with Granulomatous Pulmonary Disease

Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody

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