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

Elevated Serum Amyloid A (SAA) levels have been found in several inflammatory diseases, including sarcoidosis. SAA is suggested to be involved in sarcoidosis pathogenesis by involvement in granuloma formation and maintenance. We hypothesized that SAA serum levels would be higher in sarcoidosis compared to other non-infectious granulomatous and non-granulomatous diseases. SAA levels were measured in serum from sarcoidosis, Hypersensitivity pneumonitis (HP), and (eosinophilic) granulomatosis with polyangiitis ((E)GPA) patients. Idiopathic pulmonary fibrosis (IPF) patients were included as non-granulomatous disease group. SAA levels of patients with sarcoidosis (31.0 µg/mL), HP (23.4 µg/mL), (E)GPA (36.9 µg/mL), and IPF (22.1 µg/mL) were all higher than SAA levels of healthy controls (10.1 µg/mL). SAA levels did not differ between the diagnostic groups. When SAA serum levels were analyzed in sarcoidosis subgroups, fibrotic sarcoidosis patients showed higher SAA levels than sarcoidosis patients without fibrosis (47.8 µg/mL vs. 29.4 µg/mL, p = 0.005). To conclude, the observation that fibrotic sarcoidosis patients have higher SAA levels, together with our finding that SAA levels were also increased in IPF patients, suggests that SAA may next to granulomatous processes also reflect the process of fibrogenesis. Further studies should clarify the exact role of SAA in fibrosis and the underlying mechanisms involved.

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Role of Serum Amyloid A Protein in Various Diseases with Special Reference to Periodontal and Periapical Inflammation- A Review

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/46072.14296 ◽

2020 ◽

Author(s):

Syed Wali Peeran ◽

Ahmed Elhassan ◽

Mohammed Zameer ◽

Syed Nahid Basheer ◽

Mohammed Mustafa ◽

...

Keyword(s):

Chronic Periodontitis ◽

Serum Amyloid A ◽

Inflammatory Diseases ◽

Apical Periodontitis ◽

Serum Amyloid ◽

Amyloid A ◽

Serum Amyloid A Protein ◽

Health And Disease ◽

Periapical Inflammation

Serum Amyloid A (SAA) is an Acute-Phase Protein (APP) produced as an innate nonspecific response to any tissue damage. Hence, it plays a significant role in chronic inflammatory diseases. In particular, SAA levels increase dramatically in chronic periodontitis and chronic apical periodontitis. Recent studies suggest this role of SAA in the pathogenesis of various diseases, including chronic periodontitis and chronic apical periodontitis. Thus, the focus of this review is to sum up the current understanding of the role of SAA in health and disease and to elaborate on possible mechanisms by which SAA could play a role in the pathogenesis of chronic periodontitis and chronic apical periodontitis.

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The potential role of glycosaminoglycans in serum amyloid A fibril formation by in silico approaches

Matrix Biology Plus ◽

10.1016/j.mbplus.2021.100080 ◽

2021 ◽

pp. 100080

Author(s):

Martyna Maszota-Zieleniak ◽

Annemarie Danielsson ◽

Sergey A. Samsonov

Keyword(s):

In Silico ◽

Serum Amyloid A ◽

Potential Role ◽

Fibril Formation ◽

Serum Amyloid ◽

Amyloid A

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The role of NF-kappa B and NF-IL6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)74435-4 ◽

1993 ◽

Vol 268 (34) ◽

pp. 25624-25631

Author(s):

J C Betts ◽

J K Cheshire ◽

S Akira ◽

T Kishimoto ◽

P Woo

Keyword(s):

Gene Expression ◽

Human Serum ◽

Interleukin 6 ◽

Serum Amyloid A ◽

Interleukin 1 ◽

Serum Amyloid ◽

Nf Kappa B ◽

Amyloid A ◽

Synergistic Activation

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Molecular regulation of autophagy in a pro-inflammatory tumour microenvironment: New insight into the role of serum amyloid A

Cytokine & Growth Factor Reviews ◽

10.1016/j.cytogfr.2021.01.007 ◽

2021 ◽

Author(s):

M. du Plessis ◽

T. Davis ◽

B. Loos ◽

R. Pretorius ◽

W.J.S. de Villiers ◽

...

Keyword(s):

Serum Amyloid A ◽

Tumour Microenvironment ◽

Serum Amyloid ◽

Molecular Regulation ◽

Amyloid A ◽

Insight Into

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Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: Differences between men and women

Cytokine ◽

10.1016/j.cyto.2009.08.005 ◽

2009 ◽

Vol 48 (3) ◽

pp. 260-266 ◽

Cited By ~ 13

Author(s):

Kajsa Sjöholm ◽

Magdalena Lundgren ◽

Maja Olsson ◽

Jan W. Eriksson

Keyword(s):

Serum Amyloid A ◽

Serum Levels ◽

Serum Amyloid ◽

Adipocyte Size ◽

Men And Women ◽

Amyloid A

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Serum Amyloid a Protein and C-Reactive Protein — a Comparison of Serum Levels in Cancer and Non-Malignant Disease

Protides of the Biological Fluids ◽

10.1016/b978-0-08-030764-0.50085-9 ◽

1984 ◽

pp. 375-378

Author(s):

J.G. RAYNES ◽

E.H. COOPER

Keyword(s):

Malignant Disease ◽

Serum Amyloid A ◽

Protein A ◽

Serum Levels ◽

Serum Amyloid ◽

C Reactive Protein ◽

Reactive Protein ◽

Amyloid A ◽

Serum Amyloid A Protein

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Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2

Blood ◽

10.1182/blood-2008-03-139923 ◽

2009 ◽

Vol 113 (2) ◽

pp. 429-437 ◽

Cited By ~ 109

Author(s):

Rong L. He ◽

Jian Zhou ◽

Crystal Z. Hanson ◽

Jia Chen ◽

Ni Cheng ◽

...

Keyword(s):

Serum Amyloid A ◽

Inflammatory Diseases ◽

Serum Amyloid ◽

Proteinase K ◽

In Vivo Studies ◽

Toll Like Receptor ◽

Amyloid A ◽

Toll Like Receptor 2

Abstract The acute-phase protein serum amyloid A (SAA) is commonly considered a marker for inflammatory diseases; however, its precise role in inflammation and infection, which often result in neutrophilia, remains ambiguous. In this study, we demonstrate that SAA is a potent endogenous stimulator of granulocyte colony-stimulated factor (G-CSF), a principal cytokine-regulating granulocytosis. This effect of SAA is dependent on Toll-like receptor 2 (TLR2). Our data demonstrate that, in mouse macrophages, both G-CSF mRNA and protein were significantly increased after SAA stimulation. The induction of G-CSF was blocked by an anti-TLR2 antibody and markedly decreased in the TLR2-deficient macrophages. SAA stimulation results in the activation of nuclear factor–κB and binding activity to the CK-1 element of the G-CSF promoter region. In vitro reconstitution experiments also support that TLR2 mediates SAA-induced G-CSF expression. In addition, SAA-induced secretion of G-CSF was sensitive to heat and proteinase K treatment, yet insensitive to polymyxin B treatment, indicating that the induction is a direct effect of SAA. Finally, our in vivo studies confirmed that SAA treatment results in a significant increase in plasma G-CSF and neutrophilia, whereas these responses are ablated in G-CSF– or TLR2-deficient mice.

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