This is Part Two of a two-part series. Part One, on SLE and connective tissue disease, appeared in the February issue of The Rheumatologist (p. 1).
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Laboratory testing is an essential element in the diagnosis and management of patients with rheumatic disease. This series focuses on a diverse array of serological markers that can provide unique information on the status of the patient’s immune system that is important in clinical evaluation as well as scientific inquiry. These tests help in the diagnosis of a particular disease and, importantly, they may help monitor disease activity. Indeed, immunological testing represents one of the bedrocks of rheumatology and is a distinguishing feature of our specialty.
While there are many available tests, the approach to serology follows the traditional approach of any laboratory study. Critical in the interpretation of any serological test is determining its sensitivity (i.e., the proportion of patients with the target disorder who have a positive test), specificity (i.e., that proportion of patients who are free of the target disorder and have negative or normal test results), and positive and negative predictive values. The predictive values calculate the likelihood that disease is present or absent based on test results using the test’s sensitivity, specificity, and the probability of disease before the test is performed (pretest probability). This review will cover tests for rheumatoid arthritis (RA).
Rheumatoid factors (RFs) are antibodies directed against the Fc portion of immunoglobulin G (IgG). The RF, as currently measured in clinical practice, is an IgM RF, although other immunoglobulin types, including IgG and IgA, have been described.1,2 ELISA or nephelometry generally detects the presence of RF; latex agglutination (a test fraught with technical problems) is still sometimes used. Testing for RF is primarily used for the diagnosis of RA; however, RF may also be present in other rheumatic diseases and chronic infections.3
Patients may have detectable serum RF in a variety of rheumatic disorders, many of which share similar features, such as symmetric polyarthritis and constitutional symptoms. These include idiopathic juvenile idiopathic arthritis, palindromic rheumatism, and Sjögren’s syndrome (see Table 1, p. 19).1,2
Nonrheumatic disorders characterized by chronic antigenic stimulation (especially with circulating immune complexes or polyclonal B lymphocyte activation) commonly induce RF production (see Table 1, below right). Included in this group are indolent or chronic infection, as with subacute bacterial endocarditis or hepatitis B or C virus infection, and inflammatory or fibrosing pulmonary disorders, such as sarcoidosis, malignancy, and primary biliary cirrhosis. Rheumatoid factors have been found in up to 5% of young, healthy individuals. The reported incidence may be higher in elderly subjects without rheumatic disease, ranging from 3% to 25%.