Rheumatoid Factor

(RF)
 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 :

1. Tendons
2. Heart blood vessels
3. Subcutaneous tissues
4. lungs
• 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.
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.
Diagnosis Of RA
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
 Diagnosis Of RA
• 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

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