Immunology L7: Rheumatologic diseases Flashcards
RA Epi and Etiopath
Epidemiology: Associated with HLA-DRB1 and PTPN22 genes
Etiopath
- Hypothesized to be due to exposure of a genetically susceptible host to an arthritogenic antigen
- – Breakdown in self-tolerance
- – Chronic inflammation destroys joints
- Activation of CD4+ Th1 & Th17 cells
- Release of inflammatory mediators
- Arthritogenic Antigens: Proteins that have been modified by enzymatic conversion of Arg to citrulline
- Abs to cyclic citrullinated peptides
- RF: Ig specific for the Fc portion of IgG is present in 80% of patients
- Leads to formation of immune complexes
- Not causative, but a marker of disease activity
- Panus formation in the periphery of joints
Sx
- Digital ulnar deviation
- Ostoepenia: loss of joint spaces, bony erosions, ulnar drift (Fig)
- Rheumatoid nodule w Pallisading macrophages
Seronegative Spondyloarthropathies
- Immune-mediated musculoskeletal diseases that are initiated in genetically susceptible individuals (often HLA- B27+) in response to environmental agents or infections.
- Arthritis
- Enthesopathies (inflamm. of tendon)
Seronegative Spondyloarthropathies types
- Ankylosing spondylitis
- Reiter syndrome: Triad of arthritis, nongonococcal urethritis or cervicitis, & conjunctivitis
- Enteritis-associated arthritis: Yersinia, Salmonella, Shigella, Campylobacter
- Psoriatic or IBD-associated arthritis
CREST (Limited Scleroderma)
- Calcinosis (Calcium deposits in skin)
- Raynaud’s phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
90% have anti-centromere Abs
No lung or kidney involvement
Systemic Sclerosis (Scleroderma)
- Characterized by:
- – Extensive fibrosis in skin ± GI, kidney, lung, and other viscera
- – Vasculopathy
- – Immune dysfunction
- Mechanistic understanding is currently limited, but some recent advances; tumor Ag triggers the autoimmune response.
Etiopath:
- 40-70% have autoAbs to Topoisomerase (Scl-70), which is highly specific
- Other: auto-Ab against Centromere protein B (CENPB), topoisomerase I (TOP1), RNAP III (RPC1; encoded by POLR3A gene)
- The most highly associated markers include genes encoding immune signaling molecules
- – T-bet (Th1 differentiation; IFN production)
- – STAT4, IRF5 (type I IFN, by plasmacytoid DC)
- – TCR zeta chain
Sx
- Female : male = 3:1
- Peak incidence 50 – 60 yrs
- Striking skin changes
- Raynaud’sphenomenon(1stSxin70%)
- Dysphagia(50%)
- Hypertension
- Pulmonaryfibrosis: Pulmonary hypertension
- Renal failure
Dx: Serum CXCL4 Levels are Both Diagnostic and Prognostic
Dermatomyositis
Inflammatory disorder of skin and skeletal muscle
– Classic rash with lilac or brown discoloration of eyelids and periorbital edema
– Scaly erythematous patches over knuckles, elbows, & knees
Muscle weakness, esp. proximal
– Difficulty getting out or chair or climbing steps
Etiopath
- Can occur in adults or children – Ages 5 - 15 or 40 - 60 are peak
- AutoAbs present
- – Anti-aminoacyl tRNA synthase (Jo-1), 11-20%
- – Anti-nuclear helicase, 5-10%
- – Anti-annexin XI, 60% of pediatric pts
Sx: violet to brown discoloration is an important diagnostic clue
(Gottron’s sign).
Polymyositis
- Differs from dermatomyositis in lack of skin involvement
- – Occurs mainly in adults 30-50 yo
- May also involve heart, lung, and blood vessels
- ANA positive in 40 – 60% – 25% have anti-Jo-1 Abs
Sjogren Syndrome
- Characterized by dry eyes and mouth caused by immune-mediated destruction of lacrimal and salivary glands
- – Keratoconjunctivitis sicca
- – Xerostomia
- Most common in women between ages of 50 and 60
- ANA positive in most (50-80%)
SS-A (Ro) Abs in 75-90%
SS-B (La) Abs in 60-90%
- Lymphocytic infiltration and fibrosis of salivary glands
- **40X increased risk of B cell lymphoma (~5% of patients): Due to excessive proliferation of B cell clones **
