SYSTEMIC LUPUS ERYTHEMATHOSUS

DEFINITION
SLE is an autoimmune disease, caused by autoantibodies that recognize self antigens as foreigners, which is characterized by :
A loss of tolerance to nuclear antigens Disregulated activation of T and B cell lymphocytes Produce a large quantify of autoantibodies Formation immune complexes causing tissue and organ damage

 The prevalance of SLE is about 40 per 100.000 population in white skins and to be higher in black skins 90 % of patient is women Over 80% of cases occur in women during chilbearing years

 Causes of SLE remains unclear, but SLE can induced by environmental and hormonal factors , like : 1. Drugs , ex : procainamide, hydralazine and quinidine can inhibit DNA methylation 2. Viral infection, ex : Epstein Barr Virus 3. Ultraviolet and smoking 4. Hormonal linked X chromosom 5. Pregnancy 6. Genetic genes of MHC : HLAA1,B8,DR3 and deficiency of C1q,C2 or

 SLE is multisystemic disease, because SLE will cause multi organ damage, including skin, heart, kidneys, lungs, joints and nervous system Classification criteria which are published bu the American College of Rheumatology , combine clinical sign and symptoms with abnormalities detected in blood test

The source of autoantigens in SLE

The removal of apoptotic debris is abnormal in patients with SLE

AUTOANTIBODIES IN SLE

The Role of T and B Cells

Ag is presented to TCR in a complex with an MHC on the surface of APC But, APC must also make a second molecular interaction with T cell, called costimulatory factor ( by CD40 CD40 ligand and CD28 B7) as second signal to required T cell activation

 T Cell cytokines affect B cells by :

Stimulating cell division Switching antibody production from IgG to IgM Promoting a change in the moleculer sequence of the secreted antibody But, in people with autoimmune disease, T cell help make the production of high affinity IgG autoantibodies closely linked to tissue damage in SLE

The Role of Cytokine

Cytokines had been shown to play an essential factor in modulating immune response against foreign or self antigen

 Recently, few cytokines which have importance role in pathogenesis of SLE are TNF, IFN, IL 10, IL 12, IL 23, IL 18, IL 17, IL 21. TNF is a pleiotropic cytokine, and can either promote or reduce autoimmune. In SLE, its role is controversial. TNF promotes apoptosis and significantly affects the activity of B, T and dendritic cell But TNF blockers are associated with development of autoantibodies, such as antinuclear, anti dsDNA and anticardiolipin

 IFN potential break self tolerance by inducing dendritic cell differentiation the activation of autoreactive T and B cells. IL 12 play a pathological role in the development of autoinflammatory response in SLE patient, through the recruitment of the effector leukocytes in the inflamed tissue. And associated with progression of severe glomerulonefritis

 IL 23 IL 17 IL 23 promote activation of Th17 to produce IL 17 in SLE. IL 17 is the effector cytokines that promotes the auto inflammatory response in SLE IL 18 a factor that enhance IFN production in macrofage, T Cell and Dendritic cell. IL 18 and IL 12 potent inducer the inflammatory mediator by T cells, causing inflammatory disorder in autoimmune disease such RA

 IL 21 modulates the differentiation and function of T cell, NK cell, and Dcell. IL 21 mediate differentiation and generation of Tfh produce autokrin stimulate diff of B cell into auto antibody

TISSUE DAMAGE IN SLE

Immune complexes are central player in the tissue damage in SLE They are formed in large amounts as antinuclear antibodies bind to nuclear material in blood and tissue They are not cleared promptly because the Fc and complement receptors are deficience

Tissue Damage in SLE

 In the kidney, immune complexes accumulate in endothelial and mesengeal areal first, followed by deposition in the basement membrane and subepithelial areas And immune complexes may accumulate in the skin, nervous system, vasculer, and other organs. Immune complexes cause an influx of inflamatorry cells by activating the complement cascade and cause damage. Many of T cells, IL 17 has contribute to

PATHO GENESIS

DIAGNOSE

Erithematosus rash (rash kupu kupu)

Oral Ulcer

Discoid lupus

PROGNOSE and TREATMENT PROGNOSE Life expectancy has improved to 15 years survival rate 0f 80% today. TREATMENT Antimalaria lupus diskoid AINS arthralgia Kortikosteroid Immunosupresan SLE with SSP, nefritis , AIHA Imunoterapi