Protein biomarkers

A number of proteins in serum and synovial fluid have been studied on a one-by-one basis as biomarkers in RA. Among these, serum proteins such as C-reactive protein (CRP) offer good correlation with concurrent disease activity. Novel developments in protein chemistry and detection contributed considerable to global protein profiling in body fluids for protein marker discovery (Tab. 1).

Initial studies revealed that the heterodimer complex of the small calcium binding proteins S100A8 (calgranulin A/myeloid-related protein/MRP8) and S100A9 (calgranulin B/MRP14) was found to be increased in serum and SF of RA patients when compared to samples from patients with osteoarthritis and healthy controls [20]. S100A8 and S100A9 belong to a new class of inflammatory mediators, and function as a heterodimer [21]. These proteins are released by activated monocytes upon interaction with activated endothelial cells under inflammatory conditions. One of the functions of the heterodimer complex is to mediate leukocyte migration and adhesion to vascular endothelium. Liao et al. used tandem mass spectrometry (MS/MS), coupled with multidimensional liquid chromatography (LC) to identify biomarkers of disease severity in the synovial fluid and serum of patients with RA [22]. Significantly, levels of CRP, S100A8, S100A9 and S100A12 (cal-granulin C) were elevated in the serum of patients with erosive disease compared with patients with non-erosive RA. Preliminary studies suggest that plasma levels of the S100A8/S100A9 heterocomplex are a useful marker in monitoring efficacy of anti-TNF-a therapy [20]. Hence the combined data suggest a correlation of a selective set of local and systemic markers of inflammation with disease type in RA.

Table 1 - Overview of genomics and proteomics studies to demonstrate heterogeneity in RA

Source:

No. of patients

Procedure:

Molecular

Relation to

Biological

Refs

Serum/cell/

(RA)/healthy

Mass spec./

heterogeneity

clinical

process

tissue type

controls (HC) studied

microarray (# of genes)

Yes or No

parameters

involved

PBMC

19 RA

4,300 genes

Yes

Early vs. established RA (11 vs. 8)

Immune/growth factor activity Proliferation/neoplasia

[26]

PBMC

14 RA

10,000 genes

No

RF+ (6) vs. RF" (8)

-

[25]

PBMC

14 RA, 7 HC

10,000 genes

Yes (RA vs. HC)

Phagocytic function, inflammation (e.g., S100A8, S100A9)

[25]

Whole blood

25 RA

18,000 genes

Yes (between RA patients)

Unknown

Inflammation/ immune activity

Van der Pouw Kraan et al.

25 RA, 25 HC

Yes (RA vs. HC)

Inflammation/ immune activity

(Unpublished observations)

Serum

10 RA

Mass spec.

non-erosive (5 vs. 5)

Inflammation (e.g., CRP and S100 family members)

[20, 22] [27, 28]

Synovial

23 RA

11,500/18,000

Yes

ESR

Adaptive immunity (T-, and

tissue

genes

B-cells and APC), ectopic lymph nodes, STAT-1 pathway, tissue remodelling

FLS

19 RA

18,000 genes

Yes

Unknown

TGF-p/Activin A pathway, myofibroblast differentiation, IGF2/IGFBP5

[36]

Abbreviations: FLS, fibroblasts like synoviocytes; PBMC, Peripheral blood mononuclear cells; ESR, erythrocyte sedimentation rate

Abbreviations: FLS, fibroblasts like synoviocytes; PBMC, Peripheral blood mononuclear cells; ESR, erythrocyte sedimentation rate

Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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