Presence of Propionibacterium acnes in granulomas associates with a chronic disease course in Dutch sarcoidosis patients

Abstract

BackgroundSeveral studies demonstrated that Propionibacterium acnes (P. acnes) may be involved in sarcoidosis pathogenesis. Presence of P. acnes was found in granulomas of the majority of Japanese sarcoidosis patients. However, presence of P. acnes in tissue has never been related to sarcoidosis phenotypes and clinical outcome. Therefore, the aims of our study were to demonstrate whether P. acnes can be detected in granulomas of Dutch sarcoidosis patients and to investigate whether its presence is related to a clinical phenotype and/or course of disease.MethodsSections of formalin fixed paraffin-embedded tissue blocks of 76 sarcoidosis patients were examined by immunostaining with a P. acnes-specific monoclonal antibody (PAB antibody) using a VENTANA BenchMark ULTRA. Clinical outcome status (COS) was determined and classified into two phenotype groups: A: resolved, minimal or persistent disease without treatment (COS 1–6) and B: persistent disease with need for treatment (COS 7–9).ResultsP. acnes was detected in samples of 31 patients (41%) and located within granulomas in samples of 13 patients (17%). The frequency of P. acnes detected in granulomas at diagnosis was significantly higher in patients with phenotype B compared to patients with phenotype A (29% versus 0%, p=0.021).ConclusionPresence of P. acnes in granulomas can be confirmed in Dutch sarcoidosis patients. It is intriguing that presence of P. acnes in granulomas is more frequently found in patients with chronic disease requiring treatment. This adds to the rationale that a subgroup of sarcoidosis patients might benefit from antibiotic therapy.

Elevated Serum Amyloid a Levels Are not Specific for Sarcoidosis but Associate with a Fibrotic Pulmonary Phenotype

“…Interestingly, a major increase in SAA expression in human monocytes and macrophages was found after a combined treatment with lipopolysaccharide (LPS) and dexamethasone or methylprednisolone [ 20 ]. In a previous study, we showed the presence of C. acnes lipoteichoic acid (LTA) in granulomas of sarcoidosis patients [ 15 ]. Comparable to LPS of gram-negative bacteria, LTA is a cell wall polymer of gram-positive bacteria and plays a role in bacterial growth, membrane homeostasis, and virulence [ 35 ].…”

“…In our previous work we identified trigger-related phenotypes in sarcoidosis based on immunological sensitization for mycobacterial antigens and presence of Cutibacterial antigens in granulomas [ 14 , 15 ]. Based on its function as an acute phase protein upregulated by infections and contribution in bacterial clearance [ 1 , 16 , 17 ], together with its considered role as a biomarker in sarcoidosis, increased SAA levels may reflect underlying microbial antigens or autoantigens as triggers in a subgroup of sarcoidosis patients.…”

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

“…Formalin-fixed, paraffin-embedded tissue sections were immunohistochemically stained with the PAB antibody, a C. acnes -specific monoclonal antibody that binds to the cell membrane-bound lipoteichoic acid (LTA) of the bacterium [ 5 ]. Full methods are described elsewhere [ 6 ]. Differences in the presence of C. acnes between the patient groups was compared using the Chi-squared test.…”

“…a) Characteristics of all included patients and percentage of patients with presence of C. acnes in tissue or in tissue and granulomas. The sarcoidosis group was previously described [ 6 ]. No significant difference was observed between the three groups regarding C. acnes in tissue or C. acnes in granulomas (p=0.210 and p=0.460, respectively).…”

“…Up to now , considering granulomatous diseases , C. acnes has solely been related to the pathogenesis of sarcoidosis [ 8 ]. Presence of C. acnes has been demonstrated in tissue and granulomas of Japanese, German and Dutch sarcoidosis patients [ 5 , 6 ]. To the best of our knowledge, this is the first study that demonstrates that C. acnes can also be detected in tissue and granulomas of patients with HP and vasculitis.…”