We demonstrate the use of a camera phone as a low-cost optical detector for quantitative analysis of a high-sensitivity C-reactive protein (hs-CRP) enzyme-linked immunosorbent assay (ELISA). The camera phone was used to acquire images of the ELISA carried out in a conventional 96 well plate. Colorimetric analysis of the images was used to determine a standard curve that exhibited excellent agreement with a fitted 4-parameter logistic model (R²=0.998). The limit of detection (LOD) for this approach was determined to be 0.026 ± 0.002 μg/ml (1.035 ± 0.079 μM) CRP. Furthermore, these results were found to be in very close agreement with measurements obtained for the same assay using a laboratory-based instrument. These findings indicate the basic technology to enable low-cost quantitative home-based monitoring of an important clinical biomarker of inflammatory disease may already be present in the patient's home.
The identification of patients who will respond to anti-tumor necrosis factor alpha (anti-TNF-α) therapy will improve the efficacy, safety, and economic impact of these agents. We investigated whether killer cell immunoglobulin-like receptor (KIR) genes are related to response to anti-TNF-α therapy in patients with rheumatoid arthritis (RA). Sixty-four RA patients and 100 healthy controls were genotyped for 16 KIR genes and human leukocyte antigen-C (HLA-C) group 1/2 using polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP). Each patient received anti-TNF-α therapy (adalimumab, etanercept, or infliximab), and clinical responses were evaluated after 3 months using the disease activity score in 28 joints (DAS28). We investigated the correlations between the carriership of KIR genes, HLA-C group 1/2 genes, and clinical data with response to therapy. Patients responding to therapy showed a significantly higher frequency of KIR2DS2/KIR2DL2 (67.7% R vs. 33.3% NR; P = 0.012). A positive clinical outcome was associated with an activating KIR–HLA genotype; KIR2DS2+HLA-C group 1/2 homozygous. Inversely, non-response was associated with the relatively inhibitory KIR2DS2–HLA-C group 1/2 heterozygous genotype. The KIR and HLA-C genotype of an RA patient may provide predictive information for response to anti-TNF-α therapy.
Musculoskeletal diseases such as rheumatoid arthritis are complex multifactorial disorders that are chronic in nature and debilitating for patients. A number of drug families are available to clinicians to manage these disorders but few tests exist to target these to the most responsive patients. As a consequence, drug failure and switching to drugs with alternate modes of action is common. In parallel, a limited number of laboratory tests are available which measure biological indicators or 'biomarkers' of disease activity, autoimmune status, or joint damage. There is a growing awareness that assimilating the fields of drug selection and diagnostic tests into 'companion diagnostics' could greatly advance disease management and improve outcomes for patients. This review aims to highlight: the current applications of biomarkers in rheumatology with particular focus on companion diagnostics; developments in the fields of proteomics, genomics, microbiomics, imaging and bioinformatics and how integration of these technologies into clinical practice could support therapeutic decisions.
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