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Rheumatoid Arthritis:
Clinical Features
Systemic inflammatory dz

Symmetrical, erosive, polyarthritis (multiple joints involved; inflammn can cause damage to bone)
Criteria for classification of RA
Based on joint involvement (small joints get more points), serology, duration

Need a score of at least 6 to achieve dx
Extraarticular manifestations of RA
Rheumatoid nodules
Normocytic normochromic anemia
Interstitial lung dz
Pleuritiz/pericarditis
Sjögren's Syndrome:
What is it?
Risks?
Chronic autoimmune rheumatic and lymphoproliferative dz characterized by dry eyes, dry mouth, resulting from immunologically mediated destruction of lacrimal and salivary glands

Inc'd risk of B cell lymphoma
What antibodies are associated with Sjögren's Syndrome?
RF
ANA
Ro/SS-A or La/SS-B
HLA DR-4
Associated with RA in caucasians
Sjögren's Syndrome:
Presentation
Pulmonary--dry trachea, bronchitis, interstitial pneumonitis, pseudolymphoma, lymphoma

B Cell Lymphoma

GI: autoimmune liver dz, esophageal dysmotility, pancreatitis
Type A vs Type B Synoviocytes
Type A: phagocytes

Type B: fibroblast-like (produce mediators for joint)
What is a rheumatoid pannus?
Hypertrophied synovium (8-10 cells thick) heavily infiltrated with inflammatory cells

Invades and erodes bone and cartilage
What defines a rheumatoid factor?
Any Ab that binds Fc portion of IgG molecule
CCP Antibodies

Effect of smoking
Antibodies to Cyclic Citrullinated Peptides (CCP)

Highly specific for RA

May be present early in dz; may be assocd w/dz severity

Shared epitope (CCP-positive) + Smoking = 35x greater risk of developing RA
What are the 5 stages of RA?
Stage I :presentation of unknown Ag to T cell by APC; no syx

Stage II: Initiation of inflammatory repsonse; T/B cell prolifertn

Stage III: Nphils infiltrate synovial fluid; joint pain, swelling, morning stiffness

Stage IV: Syx = those in stage III; radiographs show periarticular osteopenia

Stage V: Erosion of subchondral bone, pannus invasion; x-rays show erosion and joint space narrowin
These T cells are involved in RA.
Th1
These T cells are involved in SLE.
Th2
These cytokines are involved in the progression of RA.

How?
TNF-alpha, IL-1

Macs: inc'd inflammn
Endothelium: inc'd cell infiltration (via inc'd adhesion molecules), inc'd angiogenesis (via inc'd VEGF)

Inc'd CRP in serum

Inc'd articular cartilage degradation (metalloproteinase synthesis)
What are the effects of IL-6?
B cell maturation, enhanced bone resorption, hepatocyte stimulus (dec'd albumin synthesis)
How can cytokines in RA be inhibited (via medication)?
-Inject soluble receptors that bind Ab's in bloodstream (means they're not allowed to bind cytokine receptors on cells), ex: TNG-alpha

-Receptor antagonists

-Flood bloodstream with anti-inflammatory cytokines
CTLA4Ig:
MOA
Prevents second-signal req'd to activate Naive T Cells

remember: need 2 receptor signals to activate T cells
IL-1Ra:
MOA
IL-1 receptor antagonist
Rituximab:
MOA
Anti-CD20
Tocilizumab:
MOA
Anti-IL-6