RHEUMATOID ARTHRITIS RA RA is a chronic systemic

  • Slides: 27
Download presentation
RHEUMATOID ARTHRITIS (RA)

RHEUMATOID ARTHRITIS (RA)

 RA is a chronic, systemic inflammatory disorder of unknown etiology characterized by the

RA is a chronic, systemic inflammatory disorder of unknown etiology characterized by the manner in which it involved joints Progressive joint destruction variable degrees of incapacitation F: M=2 -3: 1 40 -60 years old and deformity leads to

Etiology Genetic factors: Infection HLA-DR 4

Etiology Genetic factors: Infection HLA-DR 4

Etiology Rheumatoid factors (RF) are antibodies with specificity for antigenic determinates on the Fc

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

Clinical features The onset of RA is frequently heralded by prodromal symptoms such as

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

Xerostomia (Dry Mouth) Xerophthalmia (Dry Eyes)

Xerostomia (Dry Mouth) Xerophthalmia (Dry Eyes)

Rheumatoid Vasculitis RA Deformities

Rheumatoid Vasculitis RA Deformities

Laboratory Tests for RA

Laboratory Tests for RA

Laboratory findings Anemia of moderate degree ESR a useful parameter for assessing response to

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

Rheumatoid Factor § Antibodies to Fc portion of Ig. G § 75 -80% of

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

Rheumatoid Factor Ig. G Molecule Fc Portion Autoantibodies (Ig. M) directed against the Fc

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

Rheumatoid Factor RFs are human auto-Abs that react with the Fc portion of normal

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

Rheumatoid Factor RF test is approximately 65%-75% sensitive for the diagnosis The presence of

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

Condition Associated With (+) Tests for RF Rheumatologic Diseases Rheumatoid arthritis (~70%) Sjögren’s syndrome

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

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

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

Agglutination Definition: the clumping together of antigen bearing cells, microorganisms or particles in the

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

Agglutination Reactions Advantages: Easy to carry out No complicated equipment needed Can be performed

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

Agglutination (The Antigen is a Partiulate)… Qualitative: Slide Agglutination Tasts Semi Quantitative: Tube Agglutination

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

Slide Test Agglutination -- Qualitative Method �Latex agglutination

Slide Test Agglutination -- Qualitative Method �Latex agglutination

Tube Test Agglutination -- Semi Quantitative Method Tube Agglutination Tests: Identify & Titrate antibodies

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

Passive Agglutination �Converting a precipitating test to an agglutinating test �Chemically link soluble antigen

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.

Passive Agglutination- Rheumatoied Factor (Ig. M) Latex Human Ig. G (Intact Ab)

Passive Agglutination- Rheumatoied Factor (Ig. M) Latex Human Ig. G (Intact Ab)

Reverse Passive Agglutination- CRP Latex Anti CRP-Ab

Reverse Passive Agglutination- CRP Latex Anti CRP-Ab

ELISA Quantitative Method

ELISA Quantitative Method