The role of serum amyloid A staining of granulomatous tissues for the diagnosis of sarcoidosis

Huho, Albert; Foulke, Llewellyn; Jennings, Timothy A.; Koutroumpakis, Efstratios; Dalvi, Siddhartha; Chaudhry, Haroon Rashid; Chopra, Amit; Modi, Aakash; Rane, Neha; Prezant, David J.; Sheehan, Christine E.; Yucel, Recai; Patel, Mehul; Judson, Marc A.

doi:10.1016/j.rmed.2017.03.009

Cited by 19 publications

(8 citation statements)

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“…Macrophages in inflammatory lesions usually form packed aggregates as in the characteristic granulomas of sarcoidosis [72,73]. SAA has been detected by immunohistochemistry in sarcoidosis granulomas and is suggested to play a role in their maintenance [29,40]. It may be hypothesized that secreted SAA from macrophage-derived cells may reach a significant concentration in the confined intercellular milieu of granulomas and play an autocrine/paracrine role towards the neighbouring cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages

et al. 2019

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Circulating serum amyloid A (SAA) is increased in various inflammatory conditions. The human SAA protein family comprises the acute phase SAA1/SAA2, known to activate a large set of innate and adaptive immune cells, and the constitutive SAA4. The liver synthesis of SAA1/SAA2 is well-established but there is still an open debate on extrahepatic SAA expression especially in macrophages. We aimed to investigate the ability of human primary monocytes and monocyte-derived macrophages to express SAA1 , SAA2 and SAA4 at both the transcriptional and protein levels, as previous studies almost exclusively dealt with monocytic cell lines. Monocytes and derived macrophages from healthy donors were stimulated under various conditions. In parallel with SAA , pro-inflammatory IL1A , IL1B and IL6 cytokine expression was assessed. While LPS alone was non-effective, a combined LPS/dexamethasone treatment induced SAA1 and to a lesser extent SAA2 transcription in human monocytes and macrophages. In contrast, as expected, pro-inflammatory cytokine expression was strongly induced following stimulation with LPS, an effect which was dampened in the presence of dexamethasone. Furthermore, in monocytes polarized towards a pro-inflammatory M1 phenotype, SAA expression in response to LPS/dexamethasone was potentiated; a result mainly seen for SAA1 . However, a major discrepancy was observed between SAA mRNA and intracellular protein levels under the experimental conditions used. Our results demonstrate that human monocytes and macrophages can express SAA genes, mainly SAA1 in response to an inflammatory environment. While SAA is considered as a member of a large cytokine network, its expression in the monocytes-macrophages in response to LPS-dexamethasone is strikingly different from that observed for classic pro-inflammatory cytokines. As monocytes-macrophages are major players in chronic inflammatory diseases, it may be hypothesized that SAA production from macrophages may contribute to the local inflammatory microenvironment, especially when macrophages are compactly organized in granulomas as in sarcoidosis.

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Section: Discussionmentioning

confidence: 99%

Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages

et al. 2019

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“…These studies have confirmed the predominant Th1 response in sarcoidosis and particularly the key role of interferon-γ (IFN-γ) and type I IFN-driven signaling pathways (149), including significant differences in enrichment of the interferon pathway (150), but have also identified new molecular mechanisms involving Tregs (reduced suppression activity), increased apoptosis or TLR-2 signaling inhibition pathways (151). The role of histopathological staining is also under investigation, and a recent study have reported that SAA staining of sarcoidosis granulomas has an overall specificity of 84% but with a low sensitivity (44%) (152). transmethylation metabolites, molecules that could be tested in further studies as potential biomarkers.…”

Section: -Year Viewmentioning

confidence: 99%

Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis

Ramos-Casals

Retamozo

Sisó‐Almirall

et al. 2019

Expert Review of Clinical Immunology

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Introduction: Sarcoidosis is a complex systemic disease with a silent, long-term evolution, and a heterogeneous clinical presentation. The diagnostic approach is complex with no single diagnostic test that may confirm the disease.Areas Covered: A large list of serum biomarkers has been tested during the last 40 years. In this review, we analyse the potential usefulness in the diagnosis and prognosis of sarcoidosis of serum biomarkers classified according to their corresponding cellular source.Expert commentary: Diagnosis of sarcoidosis must always be approached as a multistep process based on a case-by-case integration of clinical, radiological, histological and serological data, none of which being pathognomonic. We found sIL-2R, CRP, SAA and chitotriosidase to be the best markers to confirm sarcoidosis (highest sensitivity), while ACE, gammaglobulins and lysozyme may be more useful for discarding sarcoidosis (highest specificity), taking into account that with the use of a higher cut-off we can increase specificity and with a lower cutoff we can increase sensitivity. Other biomarkers (TNF-a and CCL18) could help to identify patients with an enhanced risk of developing pulmonary fibrosis or progressive disease. The future scenario of the serological diagnostic approach of sarcoidosis will be the use of multiassays including biomarkers from different cellular sources.

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“…Serum amyloid A (SAA) has been postulated to be involved in the maintenance of the sarcoidosis granuloma by promoting antigen persistence. SAA has been frequently found within the sarcoid granuloma and is rarely observed with other granulomatous diseases [60,61]. SAA may block antigen eradication in sarcoidosis through protein aggregation and trapping of antigen within a poorly soluble protein matrix [62].…”

Section: Implications For the Scientistmentioning

confidence: 99%

A Primer on the Clinical Aspects of Sarcoidosis for the Basic and Translational Scientist

Judson

2021

JCM

Self Cite

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The immunopathogenesis of sarcoidosis remains unclear. This failure in understanding has been clinically impactful, as it has impeded the accurate diagnosis, treatment, and prevention of this disease. Unraveling the mechanisms of sarcoidosis will require input from basic and translational scientists. In order to reach this goal, scientists must have a firm grasp of the clinical aspects of the disease, including its diagnostic criteria, the immunologic defects, clinical presentations, response to therapy, risk factors, and clinical course. This manuscript will provide an overview of the clinical aspects of sarcoidosis that are particularly relevant for the basic and translational scientist. The variable phenotypic expression of the disease will be described, which may be integral in identifying immunologic disease mechanisms that may be relevant to subgroups of sarcoidosis patients. Data concerning treatment and risk factors may yield important insights concerning germane immunologic pathways involved in the development of disease. It is hoped that this manuscript will stimulate communication between scientists and clinicians that will eventually lead to improved care of sarcoidosis patients.

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The role of serum amyloid A staining of granulomatous tissues for the diagnosis of sarcoidosis

Cited by 19 publications

References 10 publications

Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages

Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages

Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis

A Primer on the Clinical Aspects of Sarcoidosis for the Basic and Translational Scientist

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