Autoimmunity


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  Notes
 
 
Slide 1 : Autoimmunity Keith J. Kaplan, MD Mayo Clinic
Slide 2 :
Slide 3 : Self-tolerance Central tolerance: primary lymphoid organs High concentration of self-antigens Clonal deletion B cell mechanisms Peripheral tolerance: peripheral tissue
Slide 4 : Mechanisms of self-tolerance Clonal deletion: destruction of lymphocytes Clonal anergy: inactivation without cell death high concentration self antigens lack of immune stimulators Clonal ignorance: do not become activated Idiotype:anti-idiotype theory
Slide 5 : Autoimmunity-mechanisms Failure of self-tolerance Molecular mimicry Release of sequestered antigens Change in self-antigens Genetic factors/MHC genes Hormonal
Slide 6 : HLA-related diseases DISEASE ALLELE RR RA DR4 6 Ank Spon B27 90-100 CAH DR3 14 Hemochrom A3 8 IDDM DR3/DR4 20 Sjogren’s DR3 10
Slide 7 : Antinuclear antibodies Against proteins, nucleic acids, nucleoproteins 3-15% population + at low titers Detection Immunofluorescence (Hep2) ELISA RIA (gold standard)
Slide 8 : Immunofluorescence Divide nuclei into nucleoplasm, nucleolus, membrane; mitoses Main patterns Homogenous Peripheral Speckled Anti-nucleolar Anti-centromere
Slide 9 : Homogenous IF pattern Diffuse nuclear IF Positive mitotic figures Anti-DNP, anti-histone, +/- anti-ds DNA SLE, drug-induced lupus
Slide 10 :
Slide 11 : Homogenous IF pattern Uniform fluorescence; + mitoses
Slide 12 : Peripheral IF pattern Rim highlighted; homogenous center Positive mitotic figures Anti-dsDNA SLE; correlates with lupus nephritis
Slide 13 : Peripheral IF pattern Membrane highlighted; + mitoses
Slide 14 : Speckled pattern Granular IF Negative mitoses Wide variety ANAs (ENAs) anti-Sm anti-RNP anti SSA/B anti-Scl-70
Slide 15 : Speckled IF pattern Granular IF; negative mitoses
Slide 16 : Anti-centromere Small dots within nucleus (46) Mitoses: dots clustered along mitotic axis CREST syndrome
Slide 17 : Anti-centromere Finite number small dots; positive mitoses
Slide 18 : Anti-nucleolar 2 to 7 large dots Negative mitoses Scleroderma (PSS) Also seen in SLE, Raynaud’s
Slide 19 : Anti-nucleolar 2 to 7 large dots; negative mitoses
Slide 20 : Anti-deoxynucleoprotein LE phenomenon Homogenous ANA 30-60% SLE patients
Slide 21 : Anti-double stranded DNA Peripheral ANA Farr RIA is gold standard Crithidia luciliae Associated with SLE/ lupus nephritis
Slide 22 : Crithidia luciliae Kinetoplast composed of ds-DNA
Slide 23 : Autoantibodies Anti-histone Homogenous ANA pattern Drug-induced lupus Anti-Smith (anti-Sm) Speckled ANA pattern Specific for SLE 30% + in SLE
Slide 24 : Autoantibodies Anti-ribonucleoprotein (anti-RNP) Speckled ANA pattern MCTD (mixed connective tissue disease) Anti-SCL-70 Speckled ANA pattern DNA topoisomerase Scleroderma
Slide 25 : SSA/SSB/SSC Speckled ANA pattern Sjogren’s syndrome SSA: neonatal lupus/heart block SSC: Sjogren’s syndrome associated with Rheumatoid arthritis
Slide 26 : Anti-mitochondrial antibody >95% primary biliary cirrhosis M2 antigen of pyruvate dehydrogenase
Slide 27 : Anti-smooth muscle antibody 70-80% + in autoimmune chronic active hepatitis
Slide 28 : Anti-parietal cell antibody Pernicious anemia 90% +
Slide 29 : Hashimoto’s thyroiditis Anti-thyroid microsomal antibody > 90%+ Anti-thyroglobulin 50%+
Slide 30 : Systemic lupus erythematosis Young females; age 15-25 ARA criteria Major autoantibodies ANA 95%+ anti-ds DNA 40-60%+ anti-Sm 30%+
Slide 31 : Drug-induced lupus Many drugs: hydralazine, procainamide Many develop antibodies; few symptoms Slow acetylators of drugs Criteria drug association limited SLE-like picture anti-histone antibody negative anti-ds DNA/anti-Sm
Slide 32 : Sjogren’s syndrome Dry eyes/dry mouth/ connective tissue disorder SSA (R0):80%+; SSB (La):50%+; SSC 3%+ SSC: 75% + when associated with RA Biopsy of minor salivary gland
Slide 33 : CREST/PSS Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasia Females, 4-5 decade, affects variety of organs Antibodies anti-centromere 95% + CREST anti-SCL-70 65% positive in PSS
Slide 34 : MCTD Females, 2-3 decade Clustering of different symptoms, not specific for any one disease Antibodies high-titer anti-ribonucleoprotein antibodies 100%+ by definition
Slide 35 : Rheumatoid arthritis Incidence 0.5% females, 0.1% males Joint pain/swelling, morning stiffness Antibodies RF: antibody (IgM) against Fc portion of IgG Heterogenous isotypes in RA anti-ds DNA 40% + Others at low titer
Slide 36 : Other diseases Polymyalgia rheumatica temporal arteritis; ESR Ankylosing spondylitis HLA-B27 +; Reiter’s, uveitis Reiter’s syndrome Arthritis, uveitis, urethritis HLA-B27; infections (Shigella, Mycoplasma)
Slide 37 : Organ-restricted diseases Wegner’s granulomatosis c-ANCA Dermatitis herpetiformis HLA-B8/DR3 IgA along D-E junction Celiac disease Anti-gliadin antibodies
Slide 38 : Organ-restricted Myastenia gravis Acetylcholine receptors a/w thymoma, thymic follicular hyperplasia, pure red cell aplasia Polymyositis/dermatomyositis Adults: 5-10% underlying malignancy Anti-Jo-1 (histidyl-tRNA-synthetase)
Slide 39 :

 



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