Chapter 116 : Autoantibody Testing in Rheumatoid Arthritis

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With new developments in the therapy of rheumatoid arthritis (RA) and evidence that therapy is most effective when started early in the disease process, it becomes increasingly important to develop criteria that will permit the accurate diagnosis of disease prior to the onset of radiographic changes. Rheumatoid factor (RF) is an antibody directed against the Fc portion of human IgG. The presence of RF in the blood is one of the diagnostic criteria used for RA. First, there may be an RA-specific overexpression of citrullinated antigens in the synovium, leading to an immune response. Second, the presence of citrullinated proteins is perhaps a common phenomenon in any inflamed (synovial) tissue but RA patients show an abnormal humoral response to them. Anti-cyclin citrullinated peptide (anti-CCP) antibody levels can change substantially in RA patients; most show elevated levels at the first visit, followed by a decrease in the majority of cases and fluctuation over time. It also has been hypothesized that the fluctuation in the anti-CCP levels may simply reflect the natural history of the autoantibody production over a course of time and that the level may peak early in the disease process, irrespective of therapeutic interventions, before declining and reaching baseline. However, more recent studies suggest that by evaluating the presence of either autoantibody (RF or anti-CCP), sensitivity for RA is increased without substantially altering the specificity.

Citation: Narain S, Kosboth M, Hahn P. 2006. Autoantibody Testing in Rheumatoid Arthritis, p 1033-1045. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch116
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Citrullination (deimination) of peptidylarginine to peptidylcitrulline by PAD.

Citation: Narain S, Kosboth M, Hahn P. 2006. Autoantibody Testing in Rheumatoid Arthritis, p 1033-1045. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch116
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Generic image for table

Comparison of features of RF assays

Citation: Narain S, Kosboth M, Hahn P. 2006. Autoantibody Testing in Rheumatoid Arthritis, p 1033-1045. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch116
Generic image for table

Comparison of the sensitivities and specificities of RF isotypes and anti-CCP combinations

Citation: Narain S, Kosboth M, Hahn P. 2006. Autoantibody Testing in Rheumatoid Arthritis, p 1033-1045. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch116
Generic image for table

Sensitivities and specificities of anti-CCP and IgM RF antibody measurements in sera of patients with RA

Citation: Narain S, Kosboth M, Hahn P. 2006. Autoantibody Testing in Rheumatoid Arthritis, p 1033-1045. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch116

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