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1. Rheumatoid Arthritis
M. Umair Naseer
Lecturer MLS
Superior University, Lahore

2. Arthritis
“arthro” = joint
“itis” = inflammation
“Arthritis can affect babies and children, as well as people in the
prime of their lives”
• Rheumatoid arthritis is an autoimmune disease in which the
normal immune response is directed against an individual's own
tissue, including the joints, tendons, and bones, resulting in
inflammation and destruction of these tissues.
• Commonest inflammatory joint disease seen in clinical
practice affecting approx 1% of population.
• Characterized by persistent inflammatory synovitis leading to
cartilage damage, bone erosions, joint deformity and disability.

3. Anatomy of the Joint
Articular/hyaline cartilage
-acts as a shock absorber
- allows for friction-free movement
- not innervated!
Synovial membrane/synovium
-secretes synovial fluid
-nourishes cartilage
-cushions the bones

4. Overview
 Age: Any age, commonly 3rd to 6th decade
 Female: male 3:1
 pattern of joint involvement could be:-
1) Polyarticular : most common
2) Oligoarticular
3) Monoarticular
 Morning joint stiffness > 1 hour and easing with physical activity is
characteristic.
 Small joints of hand and feet are typically involved.

5. Relative incidence of joint
involvement in RA
 MCP metacarpophalangeal joint (MCP joint) and PIP (Proximal Interphalangeal)
joints of hands & MTP (metatarsophalangeal joint )of feet
90%
 Knees, ankles & wrists- 80%
 Shoulders- 60%
 Elbows- 50%
 TM (Temporomandibular), Acromio - clavicular & SC joints- 30%

6. PIP Swelling

7. Ulnar Deviation, MCP Swelling,
Left Wrist Swelling

10. Rheumatoid nodule
•These are small subcutaneous nodules
present at the extensor surfaces of hand,
wrist, elbow and back in rheumatoid
arthritis patients.
•Characteristics feature of rheumatoid
arthritis
•A marker of disease activity
•Can be present even if other features of
rheumatoid Arthritis are absent

11. Laboratory investigations in RA
 CBC- TLC, DLC, Hb, ESR & GBP
 Acute phase reactants
 Rheumatoid Factor (RF)
 Anti- CCP antibodies

12. Rheumatoid Factor (RF)
 Antibodies that recognize Fc portion of IgG
 Can be IgM , IgG , IgA
 85% of patients with RA over the first 2 years become RF+
• A negative RF may be repeated 4-6 monthly for the first two year of
disease, since some patients may take 18-24 months to become
seropositive.
• PROGNISTIC VALUE- Patients with high titres of RF, in general,
tend to have POOR PROGNOSIS, MORE EXTRA ARTICULAR
MANIFESTATION.

13. PRINCIPLE-Latex agglutination test
 The RF reagent is based on an immunological reaction between
human IgG bound to biologically inert latex particles and rheumatoid
factors in the test specimen. When serum containing rheumatoid
factors is mixed with the latex reagent, visible agglutination occurs.

14. Procedure
 FOR QUALITATIVE TEST
 Place one drop (40 ul) of the RF Positive Control on field #1of the
reaction slide. Place one drop (40 ul) of the RF Negative Control on field
#2. The remaining fields are used for test specimens.
 Using a serological pipette, place 40 l of the undiluted specimens on
successive fields.
 Use different tip for each sample.
 Add one drop of RF latex reagent to each test field.
 Using the stirring sticks, mix and spread reaction mixture over entire
test field.
 Rotate the slide for 2 minutes either by hand or with a rotator (80-
100rpm) and read immediately under indirect oblique light.
 INTERPRETATION OF QUALITATIVE RESULTS A negative reaction is
indicated by a uniform milky suspension with no agglutination

15. SEMI-QUANTITATIVE Test
 Set up at least five test tubes: 1:2, 1:4, 1:8, 1:16, 1:32, etc and
dilute sample according to dilution factor on each test tube
 INTERPRETATION OF SEMI-QUANTITATIVE RESULTS
 The titer of the test is equal to the highest dilution, which
shows a visible agglutination. To determine the mg/L,
multiply the titer with the
 Dilution 1:2 would be 16.
 1: 4 would be 32
 1: 8 would be 64 and
 1:16 would be 128

16. Causes of positive test for RF
Rheumatoid arthritis
Sjogrens syndrome
Vasculitis such as polyarteritis nodosa
Sarcoidosis
Systemic lupus erythematosus
Cryoglobulinemia
Chronic liver disease
Infections- tuberculosis , bacterial endocarditis,
infectious mononucleosis, leprosy, syphilis, leishmaniasis.
Malignancies
Old age(5% women aged above 60)

17. Citrullination
 Citrullination is a chemical process and has a significant role in
different physiological processes which are involved in many
pathological diseases. Citrullination or deimination is a
posttranslational modification of protein in which arginine amino
acid is converted into citrulline amino acid. This process is
catalyzed by peptidylarginine deiminase (PAD) enzymes, which are
activated by high calcium (Ca++) concentration.

18.  Citrullination or deimination is a normal physiological reaction that occurs during cell
death. Therefore, the immune system normally is not in conflict with citrullinated
proteins. During apoptosis, the change in the physical properties of the dying cell is
followed by the clearance and ingestion of these cells by phagocytic cells. A defect in
the clearance system either in terms of efficiency or capacity may occur due to
massive cell death, and this results in the accumulation and leakage of PAD enzymes
and citrullinated peptide from the necrotizing cell which may be encountered by the
immune system
 The high calcium concentration has been suggested to occur locally in cells or in
extreme conditions like apoptosis or necrosis. Ca+2 attaches to specific binding sites
of PADs.
 citrullination is not a specific disease-related case, but it is an inflammation-
dependent process existing in diverse inflamed tissues
 anticitrullinated protein antibodies (ACPA) are targeting these citrullinated
proteins/peptides at specific tissues. Citrullination could involve many proteins, for
example, filaggrin, keratin 1, vimentin, myelin basic protein (MBP), glial fibrillary acidic
protein (GFAP), fibrin, fibrinogen, α-enolase, and collagen II; it can create and expose
nonself epitopes that induce autoantibody production

19. Anti-CCP
 IgG against synovial membrane peptides damaged via
inflammation
 Sensitivity (65%) & Specificity (95%)
 Both diagnostic & prognostic value
 Predictive of Erosive Disease
 Disease severity
 Radiologic progression
 Poor functional outcomes

20.  CCP antibodies are found in more than 75 percent of people
who have rheumatoid arthritis. They are almost never found
in people who don't have the disease.
 anti – CCP test normal range is less than 20 u/ml.

21. What do the results mean?
 Positive anti-CCP test + positive RA test:
 If you have signs or symptoms of arthritis, positive results in both the anti-CCP and RA
tests are highly predictive of rheumatoid arthritis and you may develop a more
progressive and severe form.
 Positive anti-CCP test + negative RA test
 If you have suggestive signs of rheumatoid arthritis and positive results in the anti-CCP
test but negative results in the RA test, or if you are symptomatic with weak results in both
tests, it is likely that you are in the early phase of the disease or that it will develop in the
future.
 Negative anti-CCP test + positive RA test
 If you have negative results in the anti-CCP test but positive results in the RA test, the
symptoms and clinical signs will determine the diagnosis for the disease.
 Negative anti-CCP test + negative RA test
 If your results are negative for both tests (anti-CCP and RA), it is likely that the arthritis is
due to a cause other than rheumatoid arthritis.

22. Acute Phase Reactants
Positive acute phase reactants () Negative acute phase reactants ()
Mild elevations
– Ceruloplasmin
– Complement C3 & C4
Moderate elevations
– Haptoglobulin
– Fibrinogen (ESR)
– 1 – acid glycoprotein
– 1 – proteinase inhibitor
Marked elevations
– C-reactive protein (CRP)
– Serum amyloid A protein
– Albumin
– Transferrin

23. Other Lab Abnormalities
Elevated APRs( ESR, CRP )
Thrombocytosis
Leukocytosis
ANA
30-40%
Inflammatory synovial fluid
Hypoalbuminemia

24. Radiographic Features
 Peri-articular osteopenia
 Uniform symmetric joint space narrowing
 Marginal subchondral erosions
 Joint Subluxations
 Joint destruction
 Collapse
 Ultrasound detects early soft tissue lesions.
 MRI has greatest sensitivity to detect synovitis and marrow changes.

27. Diagnostic Criterias

28. ACR Diagnostic Criteria (1987)
Description
 Morning stiffness
 Arthritis of 3 or more joints
 Arthritis of hand joints
 Symmetric arthritis
 Rheumatoid nodules
 Serum rheumatoid factor
 Radiographic changes
A person shall be said to have rheumatoid arthritis if
he or she has satisfied 4 of 7 criteria, with criteria 1-4
present for at least 6 weeks.

29. Management

30. Goals of management
 Focused on relieving pain
 Preventing damage/disability
 Patient education about the disease
 Physical Therapy for stretching and range of motion
exercises
 Occupational Therapy for splints and adaptive
devices
 Treatment should be started early and should be
individualised .
 EARLY AGGRESSIVE TREATEMNT

31. Treatment modalities for RA
 NSAIDS
 Steroids
 DMARDs (Disease-modifying antirheumatic drugs
(DMARDs) )
 Immunosuppressive therapy
 Biological therapies
 Surgery

32. Thank
you.