1. RHEUMATOID ARTHRITIS (RA)

2. RA is a chronic, systemic inflammatory disorder of unknown etiology characterized by the manner in which it involved joints
Progressive joint destruction and deformity leads to variable degrees of incapacitation
F:M=2-3: years old

3. Etiology
Genetic factors: HLA-DR4
Infection

4. Etiology
Rheumatoid factors (RF) are antibodies with specificity for antigenic determinates on the Fc portion of human or animal IgG. Currently, the most popular notion that RF arise as antibodies to “altered” autologous IgG

7. Clinical features
The onset of RA is frequently heralded by prodromal symptoms such as fatigue, anorexia, weight loss, weakness and generalized aching and stiffness
Joint disease
Extraarticular manifestations

9. Xerostomia (Dry Mouth)
Xerophthalmia (Dry Eyes)

10. Rheumatoid Vasculitis
RA Deformities

11. Laboratory Tests for RA

12. Laboratory findings Anemia of moderate degree
ESR  a useful parameter for assessing response to therapy
C-reactive protein 
RF (usually IgM)
CIC  , complements 
ANA
Anti-CCP (cyclic citrullinated peptide)

13. Rheumatoid Factor Antibodies to Fc portion of IgG
75-80% of Patients have during course of disease
Useful for prognosis

14. Rheumatoid Factor IgG Molecule Fc Portion
Autoantibodies (IgM) directed against the Fc Fragment of IgG
An Antibody to an Antibody
Their Role in RA is not understood
Antigen Binding Groove

15. Rheumatoid Factor
RFs are human auto-Abs that react with the Fc portion of normal polyclonal IgG.
Most routine clinical assays for RF detect only IgM RFs, although RFs can be any class of immunoglobulin
Named thus because their first description was in patients with rheumatoid arthritis

16. Rheumatoid Factor
RF test is approximately 65%-75% sensitive for the diagnosis
The presence of RF, even in high titers or large amounts, is not specific for RA

17. Condition Associated With (+) Tests for RF
Rheumatologic Diseases
Rheumatoid arthritis (~70%)
Sjögren’s syndrome (~90%)
Lupus (~20%)
Cryoglobulinemia syndrome (90%)
Lung Diseases
Interstitial fibrosis
Silicosis
Infections
Hepatitis C virus
Acute viral infections
Endocarditis
Tuberculosis
Miscellaneous
Sarcoidosis
Malignancies
Aging

18. Methods for detection FR
Agglutination (latex)
ELISA
RIA
Torbidometry
Nephlometry

19. Agglutination
Definition: the clumping together of antigen bearing cells, microorganisms or particles in the presence of specific antibodies
Particles may be RBCs (hemagglutination), bacterial cells (coagglutination) or inert particles such as latex or charcoal coated with antigen or antibody

20. Agglutination Reactions
Advantages:
Easy to carry out
No complicated equipment needed
Can be performed as needed
Available in pre-package kits with controls
Reactions are QUALITATIVE, i.e., positive or negative
Titers can be performed to give semi-quantitative results

21. Agglutination (The Antigen is a Partiulate)…
Qualitative: Slide Agglutination Tasts Semi Quantitative: Tube Agglutination Tests Qualitative: Primary Reaction (ELISA,…)

22. Slide Test Agglutination -- Qualitative Method
Latex agglutination

23. Tube Test Agglutination -- Semi Quantitative Method
Tube Agglutination Tests: Identify & Titrate antibodies in the patient’sserum. Titre: is defined as the reciprocal of the highest dilution of serum showing agglutination.
1/100
1/200
1/400

24. Passive Agglutination
Converting a precipitating test to an agglutinating test
Chemically link soluble antigen to inert particles such as LATEX or RBC
Addition of specific antibody will cause the particles to agglutinate
Reverse PAT: antibody linked to LATEX e.g. Lancefield grouping in Streptococci.

25. Rheumatoied Factor (IgM)
Passive Agglutination
Rheumatoied Factor (IgM)
Latex
Human IgG (Intact Ab)

26. Reverse Passive Agglutination
CRP
Latex
Latex
Anti CRP-Ab
Anti CRP-Ab

27. ELISA
Quantitative Method