Rheumatoid arthritis (RA) is a chronic autoimmune disease that predominantly impacts the peripheral joints and periarticular tissues. This systemic disease is characterized by an inflammatory process that is often symmetrical, resulting in pain, swelling, and necrosis of the joint tissue. The disease affects a significant portion of adults, with a higher incidence in women than men.
RA follows a chronic course where periods of relative wellness can alternate with phases of symptom exacerbation. If left untreated, the disease can lead to severe joint deformity or ankylosis. In advanced stages, RA can cause disability due to severe joint involvement and the presence of coexisting pathologies.
Diagnosing RA can be a challenge as it can present with few symptoms and can also be associated with other pathological conditions. The initial phase of the diagnosis is based on the patient's reported symptoms and the clinical signs observed during the medical examination, such as swelling and joint tenderness.
Laboratory investigations play a crucial role in confirming a suspected RA diagnosis. Tests used to recognize RA can include an increase in inflammation indices, blood count tests, synovial fluid examination, and the presence of certain immunological variables such as rheumatoid factor (RF) and anti-citrulline antibodies (anti-CCP).
Rheumatoid factors (RF) are a group of antibodies produced by plasma cells and directed against a portions of immunoglobulin G (IgG). These autoantibodies are usually of the IgM class but can also be IgG or IgA. They are found in various diseases characterized by immune system alterations, but are particularly prevalent in RA.
The binding of RF to IgG results in the formation of immune complexes, triggering the inflammatory response. During the progression of RA, RF correlates with the severity of the joint disease and extra-articular manifestations.
Although RF is not a specific marker of RA, its presence, coupled with clinical data compatible with RA, provides important diagnostic confirmation.
The presence of an abnormal amount of serum RF can be determined through two diagnostic investigations: the Rheuma test and the Waaler-Rose reaction. These two serological tests identify the RF in circulation using different methods.
In the Rheuma test, latex particles adhered to human IgG are used. If the patient's serum contains RF, agglutination occurs between the latex particles and the RF autoantibody present in the analyzed serum.
On the other hand, the Waaler-Rose test uses sheep's red blood cells on which rabbit IgG are adhered. If the patient's serum contains RF, a haemagglutination reaction occurs.
Both tests require a simple blood sample, and fasting from the previous evening is advisable.
The Rheuma test is more sensitive and becomes positive earlier, but is less specific. It is also more frequently positive in the presence of high RF titers in extra-rheumatoid conditions. The test can be standardized and automated, unlike the Waaler-Rose reaction, which is now almost out of use.
The Waaler-Rose reaction, while less sensitive, is decidedly more specific than the Rheuma test. This test is now mainly used to confirm the result of the Rheuma test. It can give both false positives and false negatives.
The results obtained with the Waaler-Rose test are not compatible with those obtained with the Rheuma test. The differences between the reported outcomes reflect the technical differences to highlight the presence of rheumatic factors.
In conclusion, while rheumatoid factors are found in numerous rheumatoid disorders, as well as other non-rheumatic conditions, their role is critical in the clinical definition of rheumatoid arthritis. As with all diagnostic tests, a definitive diagnosis cannot be based on the result of a single test, but must be investigated further. The recognition of IgG or IgA class RF requires specific techniques, suggesting the possibility that some of the so-called serum-negative rheumatoid arthritis are actually false negatives.
