Rheumatoid Factor (RF)

1. Rheumatoid Factor(RF)

2. Rheumatoid arthritis • Rheumatoid arthritis is a chronic autoimmune inflammatory disorder that primarily affects joints in hands and feet and other areas of the body as the disease progresses. • The disease affects the lining of joints, causing a painful swelling that can eventually result in bone erosion and joint deformity. • The most common areas affected are : • Tendons • Heart blood vessels • Subcutaneous tissues • lungs

3. RA is an autoimmune disorder, occurs when your immune system mistakenly attacks your own body's tissues. Characterized by inflammation of the synovial membranes and accumulation of synovial fluid in these membranes. • Rheumatoid arthritis is a systemic disease, meaning it can affect the entire body.

4. Pathological changes during RA : • Formation of granulated tissue that extends as vascular layer from the margin toward the center of affected joints. • Generalized lymphadenopathy. • Toxemia. Symptoms Symptoms may include • Pain • Warmth • Swelling • Morning stiffness in the joints • Nodules under the skin • If the disease has progressed, evidence on X-rays of swollen joint capsules and loss of cartilage and bone.

5. Of RA Diagnosis No test results are pathognomonic; instead, the diagnosis is made by using a combination of clinical, laboratory, and imaging features. Potentially useful laboratory studies in suspected RA include the following: • Lab diagnosis • Erythrocyte sedimentation rate • C-reactive protein level • Complete blood count • Rheumatoid factor assay titer more than 8 • Antinuclear antibody assay • Anti−cyclic citrullinated peptide and anti−mutated citrullinated vimentin assays

6. Of RA Diagnosis • Potentially useful imaging modalities include: • Radiography (first choice): Hands, wrists, knees, feet, elbows, shoulders, hips, cervical spine, and other joints as indicated • Magnetic resonance imaging: Primarily cervical spine • Ultrasonography of joints: Joints, as well as tendon sheaths, changes and degree of vascularization of the synovial membrane, and even erosions • Joint aspiration and analysis of synovial fluid may be considered, including the following: • Gram stain • Cell count • Culture • Assessment of overall appearance

7. Rheumatoid factor • Rheumatoid factor is a typical serological findings in RA. • RA and related diseases causes the production of globulin known as RF which is : • An autoantibody directed against the Fc portion of IgG and they can belong to IgM or IgG class and any of these can be detected in the blood. • That antibody binds to normal circulating IgG, forming immune complexes that are deposited in the joints. • These immune complexes can activate the complement cascade, resulting in a type III hypersensitive reaction, which leads to inflammation of the joints.

8. Rheumatoid factor test • The test for RF may be ordered when a person has signs and symptoms of RA. • An RF test may be repeated when the first test is negative and symptoms persist. • A cyclic citrullinated peptide (CCP) antibody test can help diagnose RA • The RF test may also be ordered along with other autoimmune-related tests, such as an antinuclear antibody (ANA), and other markers of inflammation, such as a C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as a complete blood count (CBC) to evaluate blood cells.

9. Principle of the Rheumatoid Factor test • The rheumatoid factor is an anti-antibody. • This can be detected in the laboratory by its ability to bind and form clumps with latex particles or red blood cells (Rose-Waaler test)that contain human Immunoglobulin G (IgG). • If the rheumatoid factor is present in the patient’s blood it attaches to the IgG coating the latex particles causing clumps. • Agglutination is considered a positive reaction that indicates the presence of rheumatoid factor at a detectable level.

10. Sample: serum or synovial fluid. • Normal range • The results of rheumatoid factor may be reported in two manners – less than 40 to 60 units per milliliters or less than 1:8 titer or 1 to 8 titer. Values may vary according to the laboratory and the kit that is used to test for the factor.

11. Rose-Waaler test • Sheep or human redblood cells coated with rabbit antired cell antibody are clumped together (agglutinated) in the presence of rheumatoid factors. • Sensitized RBCs is more sensitive than latex particle, since it can react with low concentration of antibody, so sometimes the latex maybe negative while the sensitized RBCs is positive.

12. What does the test result mean? • The RF test must be interpreted in conjunction with a person's symptoms and clinical history. • In those with symptoms and clinical signs of rheumatoid arthritis, the presence of significant concentrations of RF indicates that it is likely that they have RA. • Higher levels of RF generally correlate with more severe disease and a poorer prognosis. • A negative RF test does not rule out RA. About 20% of people with RA will have very low levels of or no detectable RF. • In these cases, a CCP antibody test may be positive and used to confirm RA.

13. What does the test result mean? • Positive RF test results may also be seen in 1-5% of healthy people and in some people with conditions such as:  • Sjögren syndrome • Systemic lupus erythematosus (lupus) • Endocarditis • Tuberculosis • Syphilis • Hiv/aids • Hepatitis • Infectious mononucleosis • Cancers such as leukemia and multiple myeloma • Parasitic infection • Disease of the liver, lung, or kidney. • The RF test is not used to diagnose or monitor these other conditions.

14. Notes • If the result is positive, then do serial dilution to determine the accurate titer of RF in the serum ( semi-quantitative method ). • The negative result from the direct agglutination doesn’t rule out RA, and positive result is not specific for RA. An example for false negative result is a Prozone Phenomena which resulted from high antibody titer ,when the number of antibody binding sites is greatly exceeded the number of epitopes.

15. Interfering Factors in the test : • High lipid or cryoglobulin give false +ve result. • High IgG level in patient serum also give false +ve result. • Activated complement.

16. A cyclic citrullinated peptide (CCP) antibody test • A cyclic citrullinated peptide (CCP) antibody test may be ordered along with or following a rheumatoid factor (RF) test to help diagnose rheumatoid arthritis (RA) and to assess the severity and probable course of the disease (prognosis). • Inflammatory markers may also be measured at this time, such as ESR and C-reactive protein (CRP). • Cyclic citrullinated peptide antibodies are autoantibodies produced by the immune system that are directed against cyclic citrullinated peptides (CCP).

17. A cyclic citrullinated peptide (CCP) antibody test • This test detects and measures anti-CCP antibodies in the blood. • Citrulline is naturally produced in the body as part of the metabolism of the amino acid arginine. • However, in joints with rheumatoid arthritis (RA), this conversion may occur at a higher rate. • Citrulline changes the protein structure and can trigger an immune response, producing autoantibodies against joint proteins. • The CCP antibody test helps to diagnose RA and can be useful in identifying people with a more rapidly erosive form of the disease

18. CCP antibody testing may also be ordered to help evaluate the likely development of RA in people with undifferentiated arthritis – those whose symptoms suggest but do not yet meet the American College of Rheumatology (ACR) criteria for RA. • According to ACR, approximately 95% of those with a positive CCP antibody will meet the criteria of RA in the future. Early detection of RA is essential for guiding treatment decisions.

19. What does the test result mean • When people with signs and symptoms of arthritis are positive for both CCP antibody and RF, it is very likely that they have RA and it is likely that they may develop a more rapidly progressive and severe form of the disease. • When people are positive for CCP antibody but not RF, or have low levels of both, and have clinical signs that suggest RA, then it is likely that they have early RA or that they will develop RA in the future. • When individuals are negative for CCP antibody but have a positive RF, then the clinical signs and symptoms are more vital in determining whether they have RA or some other inflammatory condition. • When someone is negative for both CCP antibody and RF, then it is less likely that the person has RA.

20. The CCP antibody test is relatively new. It is becoming more widely used but is still less frequently ordered than the RF test. • The anti-CCP test is thought to be slightly more specific than rheumatoid factor is when it comes to reaching a rheumatoid arthritis • CCP antibodies are rarely found in other autoimmune conditions, such as lupus, Graves disease and Sjogren syndrome, and may be detected in infections such as tuberculosis.