Principle of autoimmune diseases
Cause
Multifactorial
Genetic
Environment
Higher rate in monozygotic twins
Diseases
Rheumatoid arthritis
SLE
Psoriasis
Spondyloathrophy
Single gene defect (rare)
AIRE
Control self-Ag presenting in thymus
Cause APS-1 or APECED (with candidiasis)
FOXP3
Transcripion factor of Treg
Cause IPEX
Multigenic defect (common)
HLA
Linked most autoimmune diseases
HLA-B27
Ankylosing spondylitis
HLA-DR3
SLE
HLA-DR4
Rheumatoid arthritis
Pemphigus vulgaris
Positive and negative selection
Self-Ag
Other linked gene within MHC complex
Misfolded HLA molecule
Other
TNF-alpha, complement, ...
Infection
Non-infection
Rheumatic fever
GAS
Ankylosing spondylitis
Sexual transmitted
Chlamydia
GI
Shigella, Salmonella, Campylobacter, Yersinia
Molecular mimicry
M protein of GAS cross-react with heart muscle
Super-Ag
Non-specific potential autoreactive T cells
Homeostasis disturbance
Break immunopriviledge site
Eye
Trauma ที่ตาข้างหนึ่งแล้ว release Ag ต่อมา T cell response ต่อตาทั้ง 2 ข้าง
Testis
Mump infection
Estrogen
Alter B cell repertoire
Drugs
Procainamide
SLE
Penicillins and cephalosporins
AIHA
Criteria
Direct evidence
Indirect evidence
Transfer from mother to child
Transfer from patient to animal model
Pathology to target cells in vitro
Depletion of B cells/ T cells can reduce symptom
Induced autoimmunity by injecting self Ag
Clinical clues
Presence of Ab
HLA association
Response to immunosuppressive drugs
Disease progression
Tissue damage
Exposed cryptic peptides (new-Ag)
Limitation of identification of auto-Ag
Immune components
Hypersensitivity type 2-4
Ab
Complement
Cell mediated : CD4+, CD8+, macrophage
Cutokines