Systemic Lupus Erythemathosus

7/28/2019 Systemic Lupus Erythemathosus

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SYSTEMIC LUPUSERYTHEMATHOSUS


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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


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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


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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 : HLA-A1 B8 DR3 and deficienc of C1 C2 or


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SLE is multisystemic disease, becauseSLE 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 withabnormalities detected in blood test


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The source of autoantigens

in SLE

The removal of apoptotic debris is

abnormal in patients with SLE


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AUTOANTIBODIES IN SLE


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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


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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 cellhelp make the production of high affinity IgG

autoantibodies closely linked to tissue damage

in SLE


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The Role of Cytokine Cytokines had been shown to play an essential

factor in modulating immune response against

foreign or self antigen


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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, itsrole 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


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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 theeffector leukocytes in the inflamed tissue.

And associated with progression of severe

glomerulonefritis


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IL 23 IL 17 IL 23 promote activation of

Th17 to produce IL 17 in SLE.

IL 17 is the effector cytokines that promotesthe auto inflammatory response in SLE

IL 18 a factor that enhance IFN

production in macrofage, T Cell andDendritic cell.

IL 18 and IL 12 potent inducer the

inflammatory mediator by T cells, causinginflammatory disorder in autoimmune

disease such RA


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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


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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


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Tissue Damage in SLE


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In the kidney, immune complexes

accumulate in endothelial and mesengeal

areal first, followed by deposition in thebasement membrane and subepithelial

areas

And immune complexes may accumulate inthe skin, nervous system, vasculer, and

other organs.

Immune complexes cause an influx ofinflamatorry cells by activating the

complement cascade and cause damage.

Many of T cells, IL 17 has contribute to


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PATHO

GENESIS


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DIAGNOSE


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Erithematosus rash

(rash kupu kupu)Oral Ulcer

Discoid lupus


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PROGNOSE and TREATMENT

PROGNOSE

Life expectancy has improved to 15 years

survival rate 0f 80% today.

TREATMENT

Antimalaria lupus diskoid

AINS arthralgia

KortikosteroidImmunosupresan SLE with SSP, nefritis ,

AIHA

Imunoterapi

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Systemic Lupus Erythemathosus