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Serum

Total iron-binding capacity (TIBC)

Total iron-binding capacity (TIBC) is the measure of the maximum amount of iron needed to saturate blood transferrin, the main iron-transport protein. TIBC is used as an indirect measurement of transferrin concentrations (Hawkins, 2007; Yamanishi et al., 2003). Patients having iron deficiency display low blood levels of iron but elevated levels of TIBC.

Serum Amyloid A (SAA)

SAA is an acute phase protein, mainly produced by the liver and released in response to inflammation or infections. Indeed, SAA production is stimulated by pro-inflammatory cytokines such as IL-6, IL-1 and TNF-α (Calabrò et al., 2010).

Lipoprotein A Lp(a)

Lp(a) is a macromolecular complex composed of one molecule of Low-Density Lipoprotein (LDL) containing apolipoprotein B100 and one molecule of apolipoprotein(a). Lp(a) is synthesized by the liver and its assembly occurs at the hepatocyte cell membrane surface. Lp(a) has been shown to promote thrombosis, by preventing the conversion of plasminogen to plasmin and to participate to wound healing and tissue repair (Riches and Porter, 2012). Lp(a) has also been described as an acute-phase reactant in various disorders.

Iron

Iron is one of the most important nonorganic molecule for most forms of life. Almost all cells employ iron for fundamental activities such as energy metabolism and oxygen transport. The three main source of iron are the dietary absorption in the duodenum, the release of recycled iron from macrophages and the release of stored iron from hepatocytes (Kohgo et al., 2008). At the same time, iron excess is toxic due to its capacity to generate reactive oxygen species, underlining the importance of iron homeostasis.

Hepcidin

Hepcidin is a hormone mainly produced by hepatocytes as a precursor pro-peptide which undergoes proteolytic processing to yield its bioactive form of 25 amino-acids. Hepcidin is a key iron regulatory hormone; it inhibits iron entry into the plasma compartment by promoting the degradation of ferroportin, whose fundamental role is to release iron from tissues into the bloodstream (Nemeth et al., 2004a).

Ferritin

Ferritin is a ubiquitous and specialized protein implicated in the intracellular storage of iron. In mammals, ferritin is composed of 24 subunits forming a hallow globular complex whose cavity can store up to 4500 iron atoms (Finazzi and Arosio, 2014). Ferritin-mediated iron storage involves an oxidation process  ̶  conversion of Fe(II) to Fe(III)  ̶  that protects cells from the generation of toxic reactive oxygen species (Recalcati et al., 2008).

sgp 130 // Soluble Glycoprotein 130

Glycoprotein 130 (gp130) is a transmembrane protein which forms a hexamer with two molecules of Interleukin 6 (IL-6) and two molecules of the interleukin 6 receptor (IL-6R). gp130 is also called IL6ST, IL6-β or CD130 and can be detected in serum in a soluble form. The presence of two different soluble gp130 in human serum (90 and 110kDa), might be the result of proteolytic cleavage and/or alternative splicing of the transmembrane protein (Narazaki et al., 1993). In opposition to IL-6R, gp130 expression is not limited to IL-6 responsive cells (Hibi et al., 1990).

sRANKL (Total) // Total Soluble Receptor Activator of Nuclear Factor Kappa B Ligand

Formerly known as TNF-related activation-induced cytokine (TRANCE), the receptor activator of Nf-κB ligand (RANKL) was initially identified as an osteoprotegerin ligand (Lacey et al., 2012). RANKL is a member of the TNF superfamily and exists as a transmembrane protein and in a soluble form (after proteolytic cleavage or alternative mRNA splicing). There are three known spliced variants in human and the smallest of these three variants lacks the transmembrane and the intracellular domain and is directly secreted.

MRP 8/14 // Myeloid Related Protein 8 and Myeloid Related Protein 14 (S100A8/S100A9, Calprotectin)

Calprotectin is a heterodimer of the two calcium-binding proteins Calgranulin A (S100A8) and Calgranulin B (S100A9), also called Myeloid Related Protein (MRP) 8/MRP14. These non-covalently associated proteins constituted about 45% of the protein content of neutrophils cytosol and are 40-fold more abundant in neutrophils versus monocytes (Edgeworth et al., 1991). MRP8/14 is also present in macrophages of rheumatoid polyarthritic synovialis but not in normal tissue macrophages (Odink et al., 1987). This heterodimer belong to the alarmin family.

ICAM 1 // Intercellular Adhesion Molecule 1

ICAM-1 is also known as CD54. This adhesion molecule, expressed at the surfaces of immune system and endothelial cells, is up-regulated by cytokine stimulation. ICAM-1 has 5 Ig-like domains, a transmembrane region and a small carboxyl-terminal cytoplasmic domain. ICAM1 bind two integrin: leukocyte function associated antigen (LFA1 and CD11a/CD18) and macrophage 1 antigen (Mac-1, CD11b/CD18) (Bella et al., 1998; Yang et al., 2004).

CXCL13 // C-X-C motif chemokine 13

CXCL13 (also known as BCA-1 or BLC) is a 10.46kDa protein of 88 residues. Its receptor, CXCR5, is expressed by TFH cells in the follicle (TFH outside the follicle do not express CXCR5). For example, CXCR5 is expressed in the TFH cells which help B cells to differentiate in long lived plasma cells (Tangye et al., 2013).

Blocking the internalization of CXCR5 in mouse, with an anti-CXCL13 antibody, results in impairment of B cell homing in secondary lymphoid organ. It also attenuates symptoms in a model of autoimmune encephalomyelitis (Klimatcheva et al., 2015).

CXCL10 // C-X-C motif chemokine 10

CXCL10 is a 10 kDa protein and is also known as Interferon γ-induced protein 10 (IP-10) or small-inducible cytokine B10. This cytokine is implicated in the cell migration of leukocytes and its expression is dependent on interferon γ (IFN γ) in numerous cell types (neutrophils, monocytes, T lymphocytes, endothelial cells, fibroblast, keratinocytes, and thyrocytes among others)(Antonelli et al., 2014).

CXCL8/IL8 // C-X-C motif chemokine 8 / Interleukin 8

CXCL8 was the first characterized chemokine and was initially named IL-8. CXCL8, expressed by activated Th17 helper cells, attracts and activates neutrophils cells (Walz et al., 1987).

BAFF // B Cell Activating Factor

B-cell Activating Factor (BAFF) is a member of the TNF family and induces B cell proliferation and differentiation. The soluble form of BAFF is a 152aa with a single disulfide bond (Moore et al., 1999).

This cytokine is also called tumor necrosis factor ligand superfamily member 13b (TNFSF13b), B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) among other names.

UcOC // Undercarboxylated Osteocalcin

Osteocalcin (OC), also called bone γ-carboxyglutamic acid protein (BGP), is a 49 residues containing non-collagenous protein found in bone and dental tissues. OC is produced by osteoblasts and is a vitamin K dependent protein implicated in bone formation. Initially identified as a protein limiting bone formation, new functions such as implication in glucose metabolism, reproduction and cognition have been identified since (Ducy et al., 1996; Zoch et al., 2016). OC binds to hydroxyapatite and a fraction of the newly synthetized protein is then released in blood circulation.

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