Elsevier

Autoimmunity Reviews

Volume 8, Issue 3, January 2009, Pages 233-237
Autoimmunity Reviews

A new strategy for the early diagnosis of rheumatoid arthritis: A combined approach

https://doi.org/10.1016/j.autrev.2008.07.031Get rights and content

Abstract

Rheumatoid arthritis [RA] is one of the most common and severe autoimmune rheumatic diseases, diagnosed primarily according to clinical manifestations and radiological reports. For many years, laboratory diagnosis of rheumatoid arthritis has relied on the detection of rheumatoid factor [RF], as established by the ACR criteria. A recent test to detect antibodies towards citrullinated peptides, called the anti-CCP assay, showed a similar sensitivity but a more elevated specificity than the RF test. Our intention was the recognition of an optimal diagnostic strategy that exhibits the highest sensitivity and specificity for RA detection.

To this purpose, we examine the usefulness of autoantibodies in RA testing, evaluating the diagnostic performance of conventional and innovative assays for RF detection, and ELISA anti-CCP test, for anti-CCP antibodies detection, by a prospective study. Multiplex cytofluorimetric test appeared to be more sensitive and specific than nephelometric assay for RF detection. Hence, a novel combined approach, significantly increasing the diagnostic sensitivity for RA, was planned, employing the multiplex RF test in combination with the anti-CCP test.

Introduction

Rheumatoid arthritis [RA] is a chronic inflammatory autoimmune disease of unknown aetiology. It causes persistent synovitis, pain, joint destruction, and functional disability [1]. Irreversible joint destruction can be prevented by intervention during the first months of disease, so early diagnosis of rheumatoid arthritis is essential. Moreover, what most rheumatologists say is that the earlier RA patients are treated, the better is their prognosis [2], [3], [4]. So, there is a clear need to identify efficient diagnostic and prognostic indicators of disease.

RA can be defined as an immune-complex disease, as it involves immune complexes containing autoantibodies against soluble autoantigens [5], [6]. Particularly, an autoantibody called rheumatoid factor has been identified in about 70–80% of RA patients [7], [8].

Section snippets

Rheumatoid factor

Rheumatoid factor (RF) is an autoantibody directed against the Fc region of human IgG. Deposits of RF linked with IgG occur in various tissues, such as the synovium or joints, interfere with the normal function of the joint and promote local inflammation, resulting in tissue damages, and sometimes damage to blood vessels in the affected area [9].

In 1987 The American College of Rheumatology (ACR) has defined in details the criteria for the diagnosis of rheumatoid arthritis [10], and the only

Anti-CCP antibodies

Recently, a novel group of autoantibodies, which may have a role in the etiopathogenesis of the disease, has been described in RA.

In 1964 anti-perinuclear factor (APF) antibody, which specifically targets an antigen present in the kerato-hyaline granules surrounding the nucleus of human buccal mucosa cells, was described [21]. In 1979 anti-keratin antibodies (AKA) were identified [22] using indirect immunofluorescent (IIF) to examine unfixed rat oesophagus cryostat sections. Finally, recent

Prospective study

A prospective study was undertaken on 350 unselected serum samples from patients chosen on the basis of their clinical features, to investigate the diagnostic properties of currently used serological tests for RA. The sera, collected from January 2005 to May 2007, derived from outpatients attending clinics at the hospital “Umberto I” of Nocera Inferiore (Italy), were consecutively recruited for the study. Serum levels of two RA markers (RF and anti-CCP antibodies) were measured in the collected

Multiplex cytofluorimetric assay combined to anti-CCP test

The better performance of the cytofluorimetric assay with respect to the conventional nephelometric test, together with the enormous diagnostic specificity of anti-CCP test, brings us to plan a novel diagnostic strategy for RA, based on the use of multiplexed RF cytofluorimetric test combined to the anti-CCP test.

The combination of RF cytofluorimetric assay and anti-CCP test can provide a highly sensitive and specific screening test for RA. Indeed, when the cytofluorimetric RF test was used in

Discussion

In the last few years we have assisted at a renewed attention to rheumatoid factor as a valuable marker for RA diagnosis, despite of its relatively low specificity [31]. Furthermore, it has been shown that RF can be considered a valuable predictor of disease activity and progression of erosive RA [32], [33].

Current therapeutic protocols in RA utilises as early as possible more aggressive drugs, which aim to control disease activity and give rapid and exact diagnoses. So, there is a clear need

Take-home messages

  • The RF test is one of the ACR diagnostic criteria for RA.

  • High titres of RF are predictive of a more aggressive form of RA.

  • Anti-CCP antibodies are early and specific markers for RA diagnosis.

  • RF and anti-CCP antibodies are complementary diagnostic tools for RA.

  • The combined test [multiplex cytofluorimetric RF assay plus anti-CCP antibody test] is the most efficient tool for early RA diagnosis.

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