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Review
. 2024 Jan 4;63(1):26-33.
doi: 10.1093/rheumatology/kead405.

Calprotectin: two sides of the same coin

Valeria Carnazzo  1 , Serena Redi  1   2 , Valerio Basile  3 , Patrizia Natali  4 , Francesca Gulli  5 , Francesco Equitani  6 , Mariapaola Marino  7   8 , Umberto Basile  1
Affiliations
Review

Calprotectin: two sides of the same coin

Valeria Carnazzo et al. Rheumatology (Oxford). .

Abstract

Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.

Keywords: IBD; autoimmune diseases; faecal calprotectin; serum calprotectin.

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Figures

Figure 1.
Figure 1.
Structure of calprotectin (S100A8 and S100A9 proteins). S100A8 homodimer; individual subunits are shown in blue; S100A9 homodimer; subunits are shown in light brown; S100A8/A9 heterotetramer. Bound Ca2+ ions are shown by white spheres. Created with BioRender.com
Figure 2.
Figure 2.
Extra and intracellular biological function of calprotectin. The extracellular function is mediated by Toll-like receptor 4 (TLR-4) which is the main calprotectin receptor. The bond between the heterodimer and TLR-4 triggers signal transduction cascade that involves nuclear factor-κB (NF- κB), which translocate into the nucleus and promote the expression of pro-inflammatory cytokines chemokines, and reactive oxygen species (ROS) that drive inflammation. Created with BioRender.com
Figure 3.
Figure 3.
Calprotectin release by neutrophils and macrophages into intestinal space. After damage to the intestinal barrier, immune system cells are recruited into intestinal space and release calprotectin. This protein plays a key role to trigger inflammation. At the end, calprotectin is released through evacuation and it can be found in the stool of patients. Created with BioRender.com
Figure 4.
Figure 4.
Serum calprotectinin common autoimmune diseases. Serum calprotectin levels could be a good alternative to acute-phase protein as a biomarker in the main autoimmune diseases. In fact, high levels of serum calprotectin are detected both in systemic autoimmune diseases such as RA, SLE, SS, SSc, myasthenia gravis and vasculitis, and in organ-specific autoimmune diseases as Hashimoto’s disease, coeliac disease, IBD and Addison’s disease. Furthermore, serum calprotectin levels are increased also in haemolytic autoimmune diseases as autoimmune haemolytic anaemia. Created with BioRender.com
Figure 5.
Figure 5.
Role of serum calprotectin in autoimmune diseases. Calprotectin (CLP) may represent a connection between inflammation and the adaptive immune response. CLP contributes to the activation of CD8+ T cells during the process of activation by antigen-presenting cells via dendritic cell overexpression. CLP is an enhancer of co-stimulation of the CD40/CD40L signal leading to CD8+ T cell activation. Furthermore, CLP is an endogenous ligand of CD69. The interaction between CLP and CD69 leads to the differentiation of T cells into regulatory T cells. Created with BioRender.com
See this image and copyright information in PMC

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