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