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Biologic markers in the diagnosis and assessment of rheumatoid arthritis

Peter C Taylor, MA, PhD, FRCP
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Section Editor
James R O'Dell, MD
Deputy Editor
Paul L Romain, MD


Biologic markers, commonly termed "biomarkers," are biologic characteristics (eg, of blood or joint fluid) that can be objectively measured and serve as indicators of normal or pathologic processes or as measures of the response to therapy. In patients with rheumatoid arthritis (RA) the term is commonly applied to diagnostic or prognostic indicators, such as rheumatoid factor (RF), and to measures used to assess disease activity, such as acute phase reactants. The US National Institutes of Health has defined a biological marker (biomarker) as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" [1].

RA follows a variable disease course with regard to joint injury and functional outcomes, and early RA may be challenging to diagnose with accuracy. Thus, early identification of patients with RA and, in particular, those likely to assume a more rapidly destructive form of disease can help to target those patients most likely to benefit from early, aggressive intervention with disease-modifying agents. The response to therapy in patients with RA is typically assessed using a combination of subjective reporting and physical and laboratory findings; no single biologic measure has proven sufficient for the measurement of disease activity. These observations highlight the need for biologic markers in blood and joint fluids that may serve as reliable objective indicators of prognosis, the response to therapy, and the degree of ongoing disease activity.

This topic will review markers that are widely used in clinical practice and others proposed for such use that may serve as aids in the diagnosis of RA, for predicting prognosis, and for the assessment of disease activity. Genetic features of RA and clinical findings or associations that may have prognostic or diagnostic implications, and the diagnosis and differential diagnosis of RA are presented separately, as are more detailed discussions of RF and acute phase reactants. (See "HLA and other susceptibility genes in rheumatoid arthritis" and "Disease outcome and functional capacity in rheumatoid arthritis" and "General principles of management of rheumatoid arthritis in adults", section on 'Prognosis' and "Diagnosis and differential diagnosis of rheumatoid arthritis" and "Origin and utility of measurement of rheumatoid factors" and "Acute phase reactants".)


The main clinically useful biologic markers for the diagnosis of rheumatoid arthritis (RA) are rheumatoid factors (RF) and antibodies to citrullinated peptides (ACPA) (see 'Rheumatoid factors' below and 'Anti-citrullinated peptide antibodies' below). The presence of RF or ACPA also predicts poorer functional and radiographic outcomes. However, neither of the tests is of sufficient specificity alone to establish the diagnosis of RA, and prognosis varies widely within seropositive and seronegative patient populations, respectively.

Other commercially available biomarkers may provide additional useful information, but require further study. (See '14-3-3eta' below.)

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Literature review current through: Nov 2017. | This topic last updated: May 05, 2017.
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