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

Abstract

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.

Pathological and Tissue-Based Molecular Investigation of Granulomas in Cichlids Reared as Ornamental Fish

“…This monoclonal antibody reacted with all strains of C. acnes , and there was no cross-reactivity with other bacteria [ 23 ]. IHC with a commercially available PAB antibody (#D371-3, MBL, Nagoya, Japan) was performed by Leica BOND-III (Leica Microsystems Inc., Tokyo, Japan) using a BOND polymer refine detection kit (#DS9800, Leica Microsystems Inc.), as described in the study by Isshiki and colleagues [ 24 ]. Deparaffinization, peroxidase inhibition, antigen retrieval with BOND Epitope Retrieval Solution 1 (#AR9961, Leica Microsystems Inc.) at 100 °C for 60 min, incubation with PAB antibody (diluted 1:500) at room temperature for 8 min, and counterstaining with Mayer’s hematoxylin were performed according to the manufacturer’s instructions.…”

Potential Association of Cutibacterium acnes with Sarcoidosis as an Endogenous Hypersensitivity Infection

“…The term “ C. acnes -associated sarcoidosis” is applied to cases in which C. acnes is detected in granulomas via immunohistochemistry using the PAB antibody [ 35 ]. The detection sensitivity of C. acnes in sarcoid granulomas depends on the evaluation method [ 36 , 37 ]; an automated method of detection using a Leica system with a commercially available PAB antibody (MBL, D372-3) has been used for differential diagnosis of sarcoidosis from other granulomatous diseases.…”

“…Commensal extracellular C. acnes causes asymptomatic intracellular infection via the respiratory tract. C. acnes is the most common bacterium detected intracellularly in the peripheral lungs and mediastinal lymph nodes in humans [ 18 , 36 , 64 ]. Susceptibility to latent C. acnes infection may be partly influenced by the NOD1 allele type of the host [ 68 ] or by catalase expression of the bacterium [ 69 ].…”

Prostate Infiltration by Treg and Th17 Cells as an Immune Response to Propionibacterium acnes Infection in the Course of Benign Prostatic Hyperplasia and Prostate Cancer

“…Studies show that P. acnes can be involved in the pathogenesis of sarcoidosis. The bacterium has been detected in granulomas of some sarcoidosis patients, but not in any non-sarcoidosis ganulomas, such as tuberculosis and sarcoid reaction granulomas [ 60 , 61 ]. Beijer et al investigated that the presence of P. acnes in granulomas is associated with chronic disease requiring treatment [ 44 ].…”