S ystemic L upus E rythematosus ( SLE )

1. SystemicLupus Erythematosus(SLE)

2. Introduction: • Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of antibodies to components of the cell nucleus in association with a diverse array of clinical manifestations. • The exact aetiology of SLE is unknown. But as most autoimmune diseases it is multifactorial with genetic ,environmental , hormonal, viral, and psychoneurological influences all playing a role.

3. "Lupus" is Latin for wolf, and "erythematosus" refers to the red rash on a person's face that makes them look wolf like. • The incidence of SLE appears to be higher in women than men, with incidence of 1 in 700 among women between the ages of 20 and 60 years and with female to male ratio 10:1, also the incidence appears to be higher in black population, and still higher in Orientals. Epidemiology:

4. Etiology (Risk Factors): 1.Genetic factors Siblings of SLE patients are approximately 30 times more likely to develop SLE compared with individuals without an affected sibling. 2. Epigenetic effects The risk for SLE may be influenced by epigenetic effects such as DNA methylation and post-translational modifications of histones, which can be either inherited or environmentally modified.

5. 3.Environmental factors: • Chemical/physical factors • Drugs • Hair dyes • Tobacco smoke • Ultraviolet light • Dietary factors • L-canavanine (alfalfa sprouts) • High intake of saturated fats • Infectious agents • Bacterial DNA/endotoxins • Retroviruses - Epstein– Barr virus (EBV)

6. 4. Hormonal Factor • Low endogenous oestrogen concentrations are protective • Low androgen values in men increase risk • Use of exogenous oestrogens increases risk in women.

7. pathogenesis

8. symptoms

9. All body systems may be affected by this disease(systemic) • Gastrointestinal Tract Cardio -Vascular System • Central Nervous System Kidneys • Lungs • Mouth and Nose skin

10. Diagnosis • Guidelines provided by the American College of Rheumatology (ACR) provide the basis for accurate and standardized diagnosis of SLE. • The diagnosis of systemic lupus erythematosus requires the presence of four or more of the following 11 criteria, serially or simultaneously, during any period of observation

11. ACR Classification Criteria for Systemic Lupus Erythematosus 1 2 3 4 5 6 7 8

12. 9 10 11

13. Serological biomarkers Serological biomarkers hold a significant potential in diagnosis and monitoring of SLE. • Antinuclear Antibody (ANA) ANA is an autoantibody directed against the cells' nuclei. It is highly sensitive, being positive in 99% of SLE patients at some point in their illness. Mesured by immunofluorescent antinuclear antibody test. Antinuclear antibodies (green, FITC-labeled) from systemic lupus patients

15. ANAs are also present in healthy individuals (5-10%) and people with other connective tissue diseases, such as scleroderma and rheumatoid arthritis(not specific). • a positive ANA test alone is never enough to diagnosis systemic lupus,  the test has low diagnostic specificity for systemic lupus.  • ANA is only a screening Test.

16. Anti-dsDNA An anti-dsDNA test also checks for a certain type of antibody in blood. If someone have the anti-DNA antibody, it is highly likely he/she will have SLE. It is highly specific for lupus, with 70% of SLE patients being positive in comparison with only 0.5% of the healthy population or those with other autoimmune diseases The level of anti-DNA antibodies increases when SLE is more active. Tests used: ELISA. IFA and RIA

17. Anti-Smith Anti-Sm is an antibody directed against Smith nuclear antigen. It's rarely found in people without lupus. So a positive test can help confirm a lupus diagnosis. Up to only 30% of people with lupus have a positive anti-Sm test, but it is rarely found in people with other diseases and its incidence in healthy individuals is less than 1%. measured by one of four methods: ELISA, counterimmunoelectrophoreses (CIE), immunodiffusion, or hemagglutination

18. Other autoantibodies: • Anti-U1RNP Antibody • Anti-Ro/SSA and Anti-La/SSB Antibodies • Anti-Histone Antibodies

19. C-Reactive Protein (CRP) The test looks for inflammation, which could indicate active lupus. Results of the test could indicate changes in disease activity or in response to treatment. • Complement Complement proteins are involved in inflammation. The test can look for levels of specific complement proteins or for total complement.Complement levels are often low in patients with active disease, especially kidney disease. So doctors may use the test to gauge or monitor disease activity.

20. Erythrocyte Sedimentation Rate (ESR) ESR is used as a marker of inflammation. Inflammation could indicate lupus activity. • Complete Blood Cell Count (CBC) Abnormalities in blood cell counts, including white blood cells and red blood cells, may occur in people with lupus. For example, leucopenia thrombocytopenia .Doctors can use this test to monitor these potentially serious problems.

21. Chemistry Panel A chemistry panel is a test to assess kidney function and liver function. It gives information on electrolytes, blood sugar, cholesterol, and triglyceride levels. Abnormalities may indicate the development of complications from lupus. •  LE Cell The LE cell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil. The LE cell reaction is positive in 50%-75% of individuals with acute disseminated lupus. Positive reactions are also seen in other autoimmune disorders

22. Urine Tests for Lupus • Measurement of Glomerular Filtration Rate and Proteinuria. • Protein/Creatinine Ratio • Urinalysis: Urinalysis can be used in screening for kidney disease. The presence of protein, red blood cells, white blood cells, and cellular casts may all indicate kidney disease.

23. Treatment • There is no known cure for lupus, but there are treatments. • Nonsteroidal anti-inflammatory drugs (NSAIDs) for joint pain and fever • Corticosteroids reduce inflammation of tissues • antimalarial medications to help fight joint pain, ulcers, and rashes. • specific inhibitors , Immunosuppressive agents/chemotherapy used to treat severe lupus.

24. Is lupus fatal? • Many men and women live long, productive lives with lupus. However, it can be fatal for some people. • It depends on the severity of illness, how the body responds to treatments, and other factors. Infections are the leading cause of death in people with lupus.

25. Autoimmune Hepatitis AIH

26. Autoimmune hepatitis is a chronic (long-term) liver disease in which the immune system attacks the liver. • The cause of autoimmune hepatitis is unknown, Scientists believe that genetics and past infections may be causes of autoimmune hepatitis. • About 70% of people with autoimmune hepatitis are women. • Autoimmune hepatitis can lead to cirrhosis (scarring of the liver) and liver failure if it is not treated. • Is treated using immunosuppressive drugs (steroids).

27. Classifications: • Three types of AIH have been proposed based on differences in their immunoserologic marker.

28. symptoms • Fatigue (the most common symptom) • Abdominal pain Jaundice • Aching joints Loss of appetite • Severe itching Swollen liver Nausea • Dark urine Spider-like blood vessels o the skin • Pale stools

29. complications • Complications of autoimmune hepatitis if it progresses to cirrhosis may include: • Ascites (fluid in the abdomen) • Mental confusion • Stoppage of menstrual periods in women • Internal bleeding

30. Serologic biomarkers • ANA (antinuclear antibody): • ANA in AIH react against diverse recombinant nuclear antigens, including centromere and ribonucleoproteins • Present in 70% of type 1 AIH patients • Although non-specific, ANA represent an important diagnostic criterion of AIH. • Assessed by: • ELISA. • Indirect immunofluorescence on Hep-2 cell lines

31. Anti-SMA (anti smooth muscle antibodies): • are directed against actin and nonactin components, ncludingtubulin • Are present in 87% of patients with AIH, either as the sole marker of the disease(33%) or in conjunction with ANA (54%). • present in a variety of liver and nonliver diseases. • demonstrated in the clinical laboratory by indirect immunfluorescence.

32. Anti-LKM1 (anti liver kidney microsome 1): • Antibodies-LKM1 react with high specificity to a short linear sequence of the recombinant antigen, cytochromemono-oxygenaseCYP2D6. • Is a serologic marker of type 2 AIH • Typically occur in the absence of SMA and ANA.

33. Anti-SLA/LP ( nti soluble liver antigen) • are highly specific markers of AIH ( type 3) • A standardized enzyme immunoassay for anti-SLA/LP has been validated by Western blot using recombinant antigen • Anti-LC1 (anti liver cytosol type 1 antigen): • Are specific for AIH. • Anti-LC1 are rare in patients older than 40 year • Serum levels fluctuate with inflammatory activity in contrast to antiLKM1, so anti-LC1 is useful as markers of residual hepatocellular inflammation.

34. Diagnosis Laboratory tests:

35. Diagnosis require careful exclusion of other causes of liver disease together with the finding of a suggestive pattern of clinical, laboratory and histologic abnormalities. Scoring system provided by (IAIHG)

36. Liver biopsy • Itis essential to establish the diagnosis and evaluate disease severity to determine the need for treatment. • Liver biopsy is the golden standard for diagnosis • Lymphoplasmacytic and liver fibrosis is an indication for AIH. Plasma cell infiltrate characteristic of autoimmune hepatitis

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