Rheumatoid Factor (RF), Rheumatoid Arthritis Factor (RA factor)

Sample

1. This is done on the serum of the patient, and a fresh sample is preferred.
2. A random sample can be taken.
3. The sample can be stored at 2 to 8 °C for 24 hours.

Precautions

1. Do not use plasma.
2. Older adults have a false-positive result.
3. Lipemic serum and hemolysis give false-positive results.

Purpose of the test (Indications)

• For the diagnosis of Rheumatoid arthritis.

Pathophysiology

1. The etiology of rheumatoid arthritis is unknown.
   1. Genetic factors are important, as are hormonal and psychosomatic factors.
   2. There is evidence that immunologic factors are involved in both articular and extraarticular manifestations.
   3. In general, its incidence is 1 to 2 % in most of the populations.
2. This is a chronic inflammatory disease that affects joints, especially metacarpal and phalangeal joints.
   1. The most common joints are proximal interphalangeal joints and the wrist.
3. This is one of the autoimmune diseases.
4. Age: This is seen in 70% of the cases in the second and third decades. The peak age is 35 to 50 years.
   1. The older age group and overweight are commonly recognized risk factor for arthritis.
5. Sex: This is the disease of females with a male: female ratio of 1:3 to 5
6. The mechanism of injury is due to the production of abnormal immunoglobulin IgG against self-antigens.
   1. Possible antigens are:
      1. Self- IgG.
      2. Viral-like EBV may play a role that may suppress Ts or give rise to polyclonal activation of B-Lymphocytes. Other viruses may be blamed, like Herpes, Rubella, and Mycoplasma.
      3. Synovial lymphocytes produce IgG, which is recognized as foreign and give rise to immune complex (IgG + Anti-IgG).
7. There is the formation of anti-IgG and anti-IgM against this abnormal IgG (anti-gamma.-globulin Ab).
8. RF antibody is directed against the Fc fragment of IgG, and these are usually IgM.
9. RF factor or antibody is not specific for rheumatoid arthritis because it is also seen in other autoimmune diseases.
10. These antigen and antibody complexes activate the complement system and cause damage to the synovium.
11. Mechanism of damage to cartilage and bone:

8. Mainly  IgM is the RF Factor, and sometimes IgG and IgA may be the RF factor.
   1. RF factor as IgA when found gives rise to very severe disease.
9. Tissue other than synovium may be the site of this Ag+Ab complex reaction like :
   1. Blood vessels.
   2. Lungs.
   3. Heart.
   4. Nerves.
10. 80% of the patient are RF factor positive.
11. A negative RF factor does not rule out Rheumatoid arthritis.

Clinical criteria to diagnose rheumatoid arthritis:

1. Positive rheumatoid factor.
2. Morning stiffness at least for 6 weeks
3. pain on motion or tenderness in at least one joint for the last 6 weeks.
   1. The common site is the wrist, metacarpophalangeal, and proximal interphalangeal joints.
   2. Swelling of one joint for at least 6 weeks.
   3. Symmetrical bilateral joint swelling.
4. Subcutaneous nodules (called a rheumatoid nodule).
5. Typical radiological changes, including bony decalcification.
6. Other clinical findings are:
   1. The patient may have weight loss and fatigue.
   2. There are ocular abnormalities like the inflammatory lesion of the sclera and the episclera.
   3. The patient may develop neuropathy.
   4. There may be cardiac manifestations like pericarditis.
   5. Pulmonary manifestation is pleural effusion.
   6. Felty’s syndrome is complex of:
      1. Rheumatoid arthritis.
      2. Splenomegaly.
      3. Anemia, and neutropenia.
   7. Amyloidosis may develop as a  complication.

Diagnosis

1. CBC shows m=lymphocytosis, thrombocytosis, and raised ESR.
2. Synovial fluid examination shows mainly neutrophils (around 75%).
3. Radiological findings show a narrowing of the joints.
4. Rheumatoid factor  (RF) is positive in >70% of the cases.
5. Rapid latex agglutination
   1. This reaction depends upon the antibody present in the serum of the patient, known as a Rheumatoid factor.
   2. The strength of a positive reaction may be graded as follows:
      • 1+ = There is minimal clumping with a slightly opaque background.
      • 2+ = Small clumping with a slightly opaque fluid background.
      • 3+ = Moderate clumping with a fairly clear fluid background.
      • 4+ = Large clumps with a clear fluid background.
   3. This test can be done qualitatively by tube test where the serum is diluted.
      1. The serum can be diluted from 1:20 to 1:640 or 1:5120.
      2. Add one drop of latex solution (well-mixed).
      3. Mix all the tubes and incubate at 37 °C for 15 minutes.
      4. Centrifuge tubes for 2 minutes or  5 to 10 minutes, depending upon the centrifuge machine’s revolution.
      5. Gently resuspend and examine under the microscope for the presence of clumps (macroscopic agglutination).
         1. This is reported as IU/mL.

Normal

Source 1

• Rh- factor is negative.
  • By sheep agglutination test = Negative  (1:16)
  • By Nephelom  = <30 U/mL

Source 2

• Negative  (<60 units/mL) by nephelometry.
• Older adults may have slightly increased values.

Another source

• The RF factor is negative.
• 0 to 20 U/mL.
• In the case of titration, then its titer should be more than 1: 80.

Positive RF factor is seen in:

1. Rheumatoid arthritis.
2. Other autoimmune diseases like SLE, Sjogren’s syndrome, and Scleroderma.
3. Chronic viral infections.
4. Tuberculosis.
5. Chronic active hepatitis.
6. Syphilis.
7. Infectious mononucleosis.
8. Leukemia.
9. Biliary Cirrhosis.
10. Renal disease.

• The antinuclear antibody is positive in 55% of Rheumatoid arthritis patients.
• There are patients with RF-negative arthritis.

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