PENDAHULUAN

Lupus Eritematosus Sistemik/LES merupakan penyakit sistemik evolutif yg mengenai satu atau beberapa organ tubuh, ditandai oleh inflamasi luas pada pembuluh darah dan jaringan ikat, bersifat episodik yang diselingi oleh periode remisi.

Manifestasi klinis LES sangat bervariasi dgn perjalanan penyakit yg sulit diduga, tidak dapat diobati, dan sering berakhir dengan kematian

Karena gambaran klinisnya bervariasi dan penampilan awalnya tidak selalu menunjukkan keterlibatan multi organ, maka sering kali gejala awal sudah timbul lama, bahkan bertahun tahun sebelum didiagnosis SLE ditegakkan.

Kadang pada waktu SLE ditegakkan, kelainan ginjal sudah ditemukan

INTRODUCTION Systemic lupus erythematosus (SLE) is a

chronic autoimmune disease that can be fatal; however, with recent medical advances, fatalities are becoming increasingly rare.

The immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage.

SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system.

Lupus can occur at any age, and is most common in women, particularly of non-European descent.

ETIOLOGI

1. Faktor GENETIK 2. Faktor ENDOKRIN 3. Faktor OBAT 4. Faktor INFEKSI

Etiophathogenesis = Cellular Level

• T-Cell dysfunction • B-Cell activation

 • Abnormal Cytokine production

 • Bottom line: (the above factors and other immune

dysregulation culminates in an) abnormal abundance of autoantibodies and reduced reaction to pathogens

 T-Cell Dysfunction•  Decreased Th1

activity--> normally regulate other Tcellso Decreased IL-2,

TNF-alpha, INF-gamma 

• Increased Th2 activity--> normally regulate B cell growtho IL-4,5,6,10

  

antigen binds here

 B-Cell Activation

Abnormal Cytokine Production

 • Increased Th2-->

o Increased  IL-10--l IL-1,2 (spontaneous in ppl w/ SLE)

o IL-10 --> Th2 cytokines that activate B cells and deactivate macrophages... viscious cycle...

                    

PATOFISIOLOGI

LES timbul sebagai ekspresi klinis suatu mekanisme sekuensial, yang awalnya merupakan berbagai faktor etiologi yang masih belum diketahui dengan jelas.

Secara ringkas LES berawal dari ketidak mampuan sistem imun tubuh untuk mengebnal struktur antigen diri sehingga terjadi mekanisme autoimun.

Autoantibodi yg terbentuk akan berikatan dgn autoantigen membentuk kompleks imun yang mengendap berupa depot dalam jaringan.

Akibatnya akan terjadi aktivasi komplemen sehingga terjadi reaksi inflamasi yang menimbulkan lesi ditempat tersebut.

This time...

House is wrong...

Systemic Lupus Systemic Lupus ErythematosusErythematosusA chronic inflammatory systemic A chronic inflammatory systemic

autoimmune disease of unknown autoimmune disease of unknown etiology characterized by polyclonal etiology characterized by polyclonal B-cell activation and abnormal B-cell activation and abnormal autoantibodiesautoantibodies

MANIFESTASI KLINIS

Gejala yang timbul merupakan manifestasi aktivitas autoantibodi dan /atau depot kompleks imun dgn vaskulitis.

Semua organ tubuh dapat terserang pada suatu saat, atau pada tahap evolusi penyakit yang berbeda.

Pada awal perjalanan penyakit, gejala klinis yang muncul sangat terbatas hingga diagnosis sulit ditegakkan.

Pada perjalanan penyakit selanjutnya gejala klinis tersebut akan lebih kerap ditemukan.

Bila gejala tsb muncul berulang atau disertai gejala lain sehingga menjadi lengkap, maka diagnosis dapat lebih mudah ditegakkan

Gambaran klinis LES

LESLES

SSP20%SSP20%

Hepotomepali/Splenomegali

20%

Hepotomepali/Splenomegali

20%

Sal cerna18%

Sal cerna18%

Paru38%Paru38%

Hematologi50%

Hematologi50% Jantung

48%Jantung

48%

VaskulitisVaskulitis

Ginjal50%

Ginjal50%

Limphadenopati12-50%

Limphadenopati12-50%

Kelelahan90%

Kelelahan90%

Panas lama80-82%

Panas lama80-82%

BB turun60%

BB turun60%

Artritis/Artralgia90%

Artritis/Artralgia90%

Kulit50-58% Kulit

50-58%

SYMPTOMS

SYMPTOMS PERCENTAGE (%)

Achy joints / arthralgia 95

Fever of more than 100 degrees F / 38 degrees C 90

Arthritis / swollen joints 90

Prolonged or extreme fatigue 81

Skin Rashes 74

Anemia 71

Kidney Involvement 50

Pain in the chest on deep breathing / pleurisy 45

Butterfly-shaped rash across the cheeks and nose 42

Sun or light sensitivity / photosensitivity 30

Hair loss 27

Abnormal blood clotting problems 20

Fingers turning white and/or blue in the cold 17

Mouth or nose ulcers 12

Systemic Lupus Erythematosus

butterfly rash

Finger turns blue

Skin rashes

ImmunogeneticsImmunogenetics

Increased Risk for SLE in:Increased Risk for SLE in: HLA-DR2 (anti-DNA Abs)HLA-DR2 (anti-DNA Abs) HLA-DR3 (anti-Ro Abs)HLA-DR3 (anti-Ro Abs) Null alleles at C2 and C4 lociNull alleles at C2 and C4 loci SLE may be transmitted in an SLE may be transmitted in an

autosomal dominant pattern (family autosomal dominant pattern (family studies)studies)

SLE – Genetic SLE – Genetic SusceptibilitySusceptibility

MHC Related HLA-DR1, 2, 3, 4 Alleles of HLA-DRB1, IRF5,

and STAT4 C2 - C4 deficiency TNF- polymorphisms

Not MHC Related C1q deficiency (rare but highest risk) Chromosome 1 region 1q41-43

(PARP), region 1q23 (FcγRIIA, FcγRIIIA)

IL-10, IL-6 and MBL polymorphisms Chromosome 8.p23.1: reduced

expression of BLK and increased expression of C8orf13 (B cell tyrosine kinase), chromosome 16p11.22: integrin genes IGAM-ITGAX

B cell gene BANK1 X chromosome-linked gene IRAK1

DIAGNOSIS

   Criterion Definition

Malar Rash   Rash over the cheeks

Discoid Rash   Red raised patches

Photosensitivity  

Reaction to sunlight, resulting in the development of or increase in skin rash

Oral Ulcers   Ulcers in the nose or mouth, usually painless

Arthritis   Nonerosive arthritis involving two or more peripheral joints (arthritis in which the bones around the joints do not become destroyed)

Serositis   Pleuritis or pericarditis (inflammation of the lining of the lung or heart)

Renal Disorder  

Excessive protein in the urine (greater than 0.5 gm/day or 3+ on test sticks) and/or cellular casts (abnormal elements the urine, derived from red and/or white cells and/or kidney tubule cells)

DIAGNOSIS

   Criterion Definition

Neurologic  Disorder  

Seizures (convulsions) and/or psychosis in the absence of drugs or metabolic disturbances which are known to cause such effects

Hematologic  Disorder  

Hemolytic anemia , leukopenia , lymphopenia or thrombocytopenia. The leukopenia and lymphopenia must be detected on two or more occasions. The thrombocytopenia must be detected in the absence of drugs known to induce it.

Antinuclear  Antibody  

Positive test for antinuclear antibodies (ANA) in the absence of drugs known to induce it.  

Immunologic  Disorder  

Positive anti-double stranded anti-DNA test, positive anti-Sm test, positive antiphospholipid antibody such as anticardiolipin, or false positive syphilis test (VDRL).

Adapted from: Tan, E.M., et. al. The 1982 Revised Criteria for the Classification of SLE. Arth Rheum 25: 1271-1277.

1982 ACR (Revised 1997) SLE 1982 ACR (Revised 1997) SLE Classification CriteriaClassification Criteria

1.1. Malar (butterfly) rashMalar (butterfly) rash

2.2. Discoid lesionsDiscoid lesions

3.3. PhotosensitivityPhotosensitivity

4.4. Oral ulcersOral ulcers

5.5. Non-deforming arthritis (non-erosive for the most part)Non-deforming arthritis (non-erosive for the most part)

6.6. Serositis: pleuropericarditis, aseptic peritonitisSerositis: pleuropericarditis, aseptic peritonitis

7.7. Renal: persistent proteinuria › 0.5 g/d or ›3+ or cellular castsRenal: persistent proteinuria › 0.5 g/d or ›3+ or cellular casts

8.8. Neurologic disorders: seizures, psychosisNeurologic disorders: seizures, psychosis

9.9. Heme: hemolytic anemia; leukopenia, thrombocytopeniaHeme: hemolytic anemia; leukopenia, thrombocytopenia

10.10. Immune: anti-DNA, or anti-Sm, or APS (ACA IgG, IgM), or lupus Immune: anti-DNA, or anti-Sm, or APS (ACA IgG, IgM), or lupus anticoagulant (standard) or false + RPRanticoagulant (standard) or false + RPR

11.11. Positive FANA (fluorescent antinuclear antibody)Positive FANA (fluorescent antinuclear antibody) Definite SLE = 4 or more positive criteriaDefinite SLE = 4 or more positive criteria

Lupus Diagnostic Criteria (need 4)

1. Malar Rash: Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

2. Discoid rash: Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions

3. Photosensitivity: Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

4. Oral ulcers: Oral or nasopharyngeal ulceration, usually painless, observed by physician

From http://www.rheumatology.org/publications/classification/SLE/1997UpdateOf1982RevisedCriteriaClassificationSLE.asp?aud=pat

Gambar Rash berbentuk KUPU KUPUseperti kupu-kupu pada penderita SLE

Malarrash

Arthritis (with swelling)

Joint involvement in lupus mimics rheumatoid arthritis (RA) but milder

Arthritis (Jaccoud’s)

Photosensitivity

SLE-Clinical and Laboratory SLE-Clinical and Laboratory FeaturesFeatures

Musculoskeletal Musculoskeletal 90%90% SkinSkin 80%80% RenalRenal 50%50% CNSCNS 15%15% Severe thrombocytopeniaSevere thrombocytopenia

5-10%5-10% Positive ANAPositive ANA 95+% 95+%

Also, cardiopulmonary involvement, Also, cardiopulmonary involvement, thrombotic tendency (APS), and thrombotic tendency (APS), and “premature” or accelerated “premature” or accelerated atherosclerosis!atherosclerosis!

SLE – Pathogenetic SLE – Pathogenetic MechanismsMechanisms

Immune complex-mediated damage: glomerulonephritisImmune complex-mediated damage: glomerulonephritis

Direct autoantibody-induced damage: thrombocytopenia Direct autoantibody-induced damage: thrombocytopenia and hemolytic anemiaand hemolytic anemia

Antiphospholipid antibody-induced thrombosisAntiphospholipid antibody-induced thrombosis

Complement-mediated inflammation: CNS lupus (C3a), Complement-mediated inflammation: CNS lupus (C3a), hypoxemia, and also anti-phospholipid mediated fetal losshypoxemia, and also anti-phospholipid mediated fetal loss

Either failure of or abnormal response to normal apoptosisEither failure of or abnormal response to normal apoptosis

Immune-complex Injury in Immune-complex Injury in SLESLE

DNA + Anti-DNA = DNA - Anti-DNA DNA + Anti-DNA = DNA - Anti-DNA complexcomplex

C3 C4C3 C4

Tissue InjuryTissue Injury

SLE: Anti-DNA, C3, C4SLE: Anti-DNA, C3, C4

SLE – THE USE OF SLE – THE USE OF POSITIVE ANASPOSITIVE ANAS

A positive ANA alone is not enough to diagnose SLE! A positive ANA alone is not enough to diagnose SLE! Are there other autoantibodies present, e.g., anti-DNA, anti-Are there other autoantibodies present, e.g., anti-DNA, anti-

Sm, anti-Ro?Sm, anti-Ro?

What are the patient’s clinical features that suggest What are the patient’s clinical features that suggest lupus? lupus?

Photosensitivity, serositis, thrombocytopenia, proteinuria, Photosensitivity, serositis, thrombocytopenia, proteinuria,

skin rashes?skin rashes?

An ANA should only be ordered if the clinical picture An ANA should only be ordered if the clinical picture warrants warrants it! it! About 6-10% of people in the general population are ANA (+) About 6-10% of people in the general population are ANA (+)

SLE – Cardiac DiseaseSLE – Cardiac Disease

PericarditisPericarditis Inflammatory fluid Inflammatory fluid Rarely tamponadeRarely tamponade

MyocarditisMyocarditis Coronary vasculitis – RareCoronary vasculitis – Rare Libmann-Sachs endocarditisLibmann-Sachs endocarditis Premature or accelerated Premature or accelerated

atherosclerotic diseaseatherosclerotic disease

Causes of Cardiovascular Complications in Causes of Cardiovascular Complications in LupusLupus

Procoagulant State (multifactorial, APS)

Strokes PVD

Premature or Accelerated Atherosclerosis

MIs

CV System Pericarditis 6-45% of patients: low likelihood of tamponade or constrictive

type. <10% with myocarditis Libman-Sacks endocarditis

1-4 mm vegetations of accumulations of immune complexes and mononuclear cells on mitral, tricuspid or aortic valves Risk of thromboembolism or secondary infective endocarditis (abx prophy)

Aortic insufficiency is the most common valvular abnormality. Heart disease

Contributes to bimodal pattern of mortality from lupus A study from U of Pittsburgh comparing rates of MI to that of Framingham Offspring

Study data showed that risk of MI was 50x higher in woman with lupus ages 35-44 and 2.5-4x higher in older age groups

Autopsy data shows CAD in 40% of SLE patients as opposed to only 2% of age matched controls.

Atherosclerotic plaque burden (via carotid intima media thickness measurements and by coronary calcium scores) is higher in patients with SLE than in controls

“Lupus dyslipoproteinemia” is low HDL, high TG, normal or only slightly elevated LDL, increased lipoprotein(a): this appears to correlate with disease activity

Means of prevention focus on risk factor management and inflammation control, but no clear guidelines are available as of yet.

SLE – Heme SLE – Heme ManifestationsManifestations Autoimmune hemolytic anemia (AHA)Autoimmune hemolytic anemia (AHA) Autoimmune thrombocytopenia, ITP-likeAutoimmune thrombocytopenia, ITP-like LeukopeniaLeukopenia PancytopeniaPancytopenia LymphopeniaLymphopenia Anti-phospholipid antibodies – False Anti-phospholipid antibodies – False

positive positive RPRs (neg FTA)RPRs (neg FTA) LymphadenopathyLymphadenopathy Rarely, aplastic anemia (from anti-stem Rarely, aplastic anemia (from anti-stem

cell antibodies)cell antibodies)

CNS LupusCNS Lupus

Seizures - EpilepsySeizures - Epilepsy Strokes with hemiparesisStrokes with hemiparesis Coma (“lupus cerebritis”)Coma (“lupus cerebritis”) Cranial nerve and peripheral neuropathiesCranial nerve and peripheral neuropathies Brain stem/cord lesionsBrain stem/cord lesions Aseptic meningitisAseptic meningitis Transverse myelitisTransverse myelitis Psychiatric: memory loss, cognitive Psychiatric: memory loss, cognitive

changeschanges Myasthenia gravis, multiple-sclerosis likeMyasthenia gravis, multiple-sclerosis like

Lungs and Pleura

Over 30% will have pleuritis or an effusion over the course of their disease Fluid is exudative, normal glucose, high

protein, WBC <10,000 (neutrophilic or lymphocytic), decreased complement

Can have pneumonitis, pulmonary hemorrhage (rare but often fatal), PE, pulmonary HTN Pulmonary HTN more likely to be associated

with Raynaud’s

Anti-Phospholipid Antibody Syndrome Anti-Phospholipid Antibody Syndrome (APS) – Clinical and Laboratory (APS) – Clinical and Laboratory FeaturesFeatures Recurrent arterial and/or venous thrombosis (thrombophilia)Recurrent arterial and/or venous thrombosis (thrombophilia) Recurrent fetal loss (usually late miscarriages)Recurrent fetal loss (usually late miscarriages) Thrombocytopenia, autoimmune hemolytic anemia (AHA)Thrombocytopenia, autoimmune hemolytic anemia (AHA) Livedo reticularisLivedo reticularis But also: heart valve vegetations, chorea, transverse But also: heart valve vegetations, chorea, transverse

myelitis, multiple sclerosis-like syndrome, cognitive myelitis, multiple sclerosis-like syndrome, cognitive dysfunction, AVNdysfunction, AVN

Labs: positive antiphospholipid (APL) Abs, and/or (+) lupus Labs: positive antiphospholipid (APL) Abs, and/or (+) lupus anticoagulant (LAC), and/or (+) anti-anticoagulant (LAC), and/or (+) anti-22-glycoprotein 1 (anti--glycoprotein 1 (anti-22GPI) antibodiesGPI) antibodies

There is no consensus yet as to what clinical and lab features There is no consensus yet as to what clinical and lab features

should be included or excluded in the definition of APS! should be included or excluded in the definition of APS!

SLE: Therapeutic ApproachesSLE: Therapeutic Approaches

NSAIDS: but be careful with ibuprofen-other NSAIDS and aseptic meningitisNSAIDS: but be careful with ibuprofen-other NSAIDS and aseptic meningitis Corticosteroids, including IV “pulse” RxCorticosteroids, including IV “pulse” Rx Hydroxychloroquine (Plaquenil®): controls and prevents SLE, Hydroxychloroquine (Plaquenil®): controls and prevents SLE,

anticoagulant, anticoagulant, cardioprotectivecardioprotective Cytotoxics: cyclophosphamide (Cytoxan®), MTX, mycophenolate mophetil Cytotoxics: cyclophosphamide (Cytoxan®), MTX, mycophenolate mophetil (CellCept®), azathioprine (Imuran®)(CellCept®), azathioprine (Imuran®) IVIG: short-lived correction of thrombocytopeniaIVIG: short-lived correction of thrombocytopenia** Plasmapheresis: not well documented. Used for CAPSPlasmapheresis: not well documented. Used for CAPS Experimental: LJP394 (B cell tolerogen for anti-DNA Abs), CTLA4Ig Experimental: LJP394 (B cell tolerogen for anti-DNA Abs), CTLA4Ig (abatacept), anti-C5 (? efficacy), anti-T and B cell targets (CD40-CD40L, (abatacept), anti-C5 (? efficacy), anti-T and B cell targets (CD40-CD40L, rituximab (Rituxan®), anti-BLYS Rx (lymphostat-B, belimumab), MEDI-rituximab (Rituxan®), anti-BLYS Rx (lymphostat-B, belimumab), MEDI- 545, an anti-IFN 545, an anti-IFN monoclonal antibody (MedImmune, Inc.), kinase monoclonal antibody (MedImmune, Inc.), kinase

inhibitors, prolactin inhibitors, etcinhibitors, prolactin inhibitors, etc Experimental combination Rx: Cytoxan® + CTLA4Ig, other combos, etcExperimental combination Rx: Cytoxan® + CTLA4Ig, other combos, etc Bone marrow approaches: ablative therapy and stem cell transplant Bone marrow approaches: ablative therapy and stem cell transplant *Gonzalez EB, Truslow W, Miller SB. Intravenous immunoglobulin (IVIG) offers short-term limited benefit in lupus *Gonzalez EB, Truslow W, Miller SB. Intravenous immunoglobulin (IVIG) offers short-term limited benefit in lupus

thrombocytopenia. Arthritis & Rheumatism 36: S228, 1993 thrombocytopenia. Arthritis & Rheumatism 36: S228, 1993

The FDA approved Drugs for Lupus

Corticosteriods -  including prednisone, prednisolone, methylprednisolone, and hydrocortisone Antimalarial - (e.g. hydroxychloroquine) - used as an anti-inflammatory drug Anti inflammatory - e.g. Aspirin, Acetaminophen, NSAID (Ibuprofen) - used to treat pain and swelling associated with inflammation

Corticosteriods-Also known as glucocortocoids,  cortisone, or just steroids - Synthetic drugs designed to mimic the actions of the body's naturally occuring hormones specifically cortisol - Cortisol helps regulate blood pressure and the immune     system, and it is the body’s most potent  anti-inflammatory hormone - Corticosteroids help to reduce swelling, tenderness and pain associated with inflamation - Works by lessening immune system response  -Prednisone is the most popular corticosteroiid prescribed to SLE patients  - Side effect include changes in appearance and mood and increased risk of osteoporosis   

 

Anti Malarial Drugs

Used in conjunction with steroids Help to reduce inflammation and thrombosis Lessen the symptoms of SLE by:    - reducing the production of auto antibodies    - protecting against UV radiation    - improve skin lesions Two most common types of Antimalarials used for treating SLE:    -Hydrochloroquine    -Chloroquine  Side Effects are usually mild such as upset stomach    

Mechanism for HydroxychloroquineHydroxychloroquine reduces inflammation by blocking the activation of the Toll-like Receptors on Plasmacytoid Dendritic Cells. Toll-like Receptors are responsible for the maturation of dendritic cells by promoting the production of Interferon.

Inhibiting the dendritic cells via decreased TLR signaling helps to reduce the inflammatory cells

Anti Inflammatory- Used to treat inflammation and pain - Most common treatment form lupus patients (the only           medication needed to control the disease for many) - Inexpensive and available OTC - Minimal side effects    - Can cause GI tract irritation - Examples include Aspirin, Acetaminophen,  and Non-steroidal anti inflammatory drugs (NSAID) such as Ibuprofen

Immunosuppressives -Used to control inflammation and an overactive immune system -Usually used after treatment with corticoidsteroids is ineffective

 - Common immunosuppressives used in treating lupus include:        -Cylcophosphoamide         -Shown to improve kidney and lung disease    -Methotrexate        -One of the best known treatments for rheumatoid arthritis    -Azathioprine        -Helps to lower steroid dosage and improve liver and                 kidney disease

-Obviously there are serious side effects such as reduced ability to fight off infection

Monoclonal Antibody Therapy

Monoclonal antibodies target specific molecules known to contribute to SLE

Examples:    -Anti-Interleukin 6        -Targets IL-6 which is known to cause inflammation    -Anti TNF therapy        - Helps treat arthritis which occurs in lupus *find mech        - However it has also been shown to cause drug-induced             lupus *find mech    -Anti-Interleukin 10        - Targets IL-10 which is important for activation of B-cells

Because SLE is a complex disease and involves many factors, research for SLE has taken on many direction

Autoantibodies ANA: against targets in the nucleus, but only those which have

intrinsic immunological activity: i.e.. They can activate the innate immune system via Toll-like receptors

Anti DS-DNA in particular recognizes DNA in complex with nucleosome components (histone-derived peptides in particular)

Can correlate with nephritis Immune complexes with anti-DNA ab/DNA can increase the expression of IFN-

via plamacytoid dendritic cells Anti-Sm: detects ribonucleoproteins involved in processing of

mRNA; doesn’t track with disease, specific for lupus SSA/Ro and SSB/La: detect ribonucleoproteins, associated with

SICCA syndrome and photosensitivity Anti NMDA to subunits NR2a and NR2b may be associated with

neuropsychiatric symptoms “Antiphospholipid” antibodies are ab against phospholipid-binding

proteins or phospholipids that are prothrombogenic. Ex: lupus anticoagulant, anticardiolipin, and anti beta2-glycoprotein I

Mechanism SummaryDefects in clearance of apoptotic cells can lead to exposure of intracellular immunogenic components which can be taken up by DC and presented to autoreactive B cells (made this way during random somatic hypermutation).In the right genetic environment, these B cells may become activated to produce autoantibodies.Polymorphisms or mutations in genes in numerous steps of B-cell regulation or IFN-responsiveness can predispose to SLE (FcRIIa, IRF5,

STAT4, BLK)

Why are autoantibodies so bad?Renal disease

IgA, IgM, IgG and complement deposition in the mesangium and subendothelial and subepithelial of the GBM that results in complement activation and recruitment of inflammatory cells that result in tissue destruction.

Cross reactivity of anti-DS DNA antibodies with -actinin may also result in a direct focusing of complement activation

Skin disease Inflammation and breakdown of the dermal-epidermal

junction. UV exposure can worsen because it promotes apoptosis in

the skin resulting in autoantibody binding and tissue injury via complement activation or inflammatory cell activation

Anti-Ro antibodies are associated with skin flares

Why are autoantibodies so bad? In the CNS, vasculitis is rare

Anti-NMDA receptor antibodies may contribute to cerebral lupus phenotypes

See more microinfarcts and degeneration or proliferative changes in blood vessels, thought to be related to IC deposition

Antiphospholipid abs may contribute to thrombotic events anywhere in the body aPLs bind to endothelial cells, monocytes,

neutrophils and platelets causing inflammation and procoagulant release

This process is dependent on complement activation

Renal: A) Proteinuria (>500 mg/24hrs)

B) Cellular casts

Blood tests in the diagnosis of SLE

The anti-nuclear antibody test (ANA) to determine if autoantibodies to cell nuclei are present in the blood.

The anti-DNA antibody test to determine if there are antibodies to the genetic material in the cell .

The anti-Sm antibody test to determine if there are antibodies to Sm, which is a ribonucleoprotein found in the cell nucleus .

Tests to examine the total level of serum (blood) complement (a group of proteins which can be consumed in immune reactions), and specific levels of complement proteins C3 and C4.

Anti-nuclear antibodies (ANA)

Rim

Nucleolar

Diffuse

Speckled

LE Cell

The LE cell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil.

LE cells may appear in rosettes where there are several neutrophils vying for an individual complement covered protein.

Renal (Kidney) Manifestations

50-70% of all lupus patients experience renal developments.

Most Dangerous: Glomerulonephritis

where at least 50% of the glomeruli have cellular proliferation Glomeruli – capillary

beds in the kidney that filter the blood.

Renal Failure because of Glomerulonephritis is the leading cause of death among lupus patients.

Normal

Glomerulonephritis

Summary

Lupus = Autoimmunity Systemic and affects connective tissue

Caused by malfunctions of: T-cells B-cells Complement System Signal Transduction

Can be lethal or not Unique to each individual