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Clinical applications of auto antibodies

Clinical applications of auto antibodies. Brig Tahir Aziz Ahmed Consultant Immunologist Armed Forces Institute of Pathology (AFIP) Rawalpindi-Pakistan. Dr Paul Ehrlich. 1854-1915 German Nobel laureate Diphtheria antiserum (with von Boehring) only Boehring won Nobel prize-1901

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Clinical applications of auto antibodies

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  1. Clinical applications of auto antibodies Brig Tahir Aziz Ahmed Consultant Immunologist Armed Forces Institute of Pathology (AFIP) Rawalpindi-Pakistan

  2. Dr Paul Ehrlich • 1854-1915 • German • Nobel laureate • Diphtheria antiserum (with von Boehring) only Boehring won Nobel prize-1901 Ehrlich won it for Salvarsan a treatment for Syphilis-five years later • Side-chain theory • Dr Paul Ehrlich’s magic bullet 1945

  3. Auto antibodies • Horror autotoxicus • Auto antibodies relatively easy to detect • Some well defined disease and subset associations • Some auto antibodies with defined role in immunopathogenesis • Antibody levels may relate with disease activity

  4. Thyroid • Thyroid • Anti thyroid peroxidase antibodies (anti thyroid microsomal antibodies) • Anti thyroglobulin antibodies • Anti TSH receptor antibodies • Activating antibodies (Grave’s ophthalmopathy) • Inhibitory antibodies (thyrotropin binding inhibitory immunoglobulins TBII-Thyroiditis)

  5. Anti thyroid microsomal & thyroglobulin antibodies

  6. Anti Thyroglobulin antibodies < 100 IU/ml Normal > 100 IU/ml Elevated 100-500 IU/ml High 501-1000 IU/ml Very high >1000 IU/ml Extremely high (103 positive out of 248. One year local unpublished data)

  7. Anti thyroid peroxidase antibodies < 30 IU/ml Normal 30-300 IU/ml High >300 IU/ml Very high (109 positive out of 496. One year local data unpublished)

  8. When to test for thyroid antibodies • Autoimmune thyroid disease • Grave’s disease • Hashimotos thyroiditis • Postpartum thyroiditis (OR: 11.5) • Idiopathic painless thyroiditis • Thyroglobulin monitoring in thyroid cancer • Recurrent miscarraige (OR: 3.73) • Unexplained subfertility (OR: 1.5) • Preterm birth (OR: 1.9) • Autoimmune polyendocrine syndromes

  9. Anti thyroid antibodies in subclinical hypothyroidism TPO Abs positive: 11.2% of 1500 euthyroid pregnant Pakistani women Miscarriage rate: 36.3% (1.8% in Ab neg women) Prematurity: 26.8% (8% in Ab neg women) (Ghaffor F et al. JCPSP 2006: 16(7); 468-471) • Anti thyroid antibodies in population surveys • Overt hypothyroidism, Thyrotoxicosis = 0.4% • Subclinical hypothyroidism = 4.0% • TPO antibodies 8.6% males; 18.5% females (Hoodgendoorn et al. Clin Chemistry 2006: 52(1); 104-111)

  10. Pregnancy loss • Anti cardiolipin antibodies IgG, IgA, IgM • Anti beta-2 glycoprotien 1 antibodies IgG, IgA, IgM • Lupus anti coagulant test Test to be positive with an interval of 8 weeks

  11. Infertility • Anti sperm agglutinating antibodies (12 /83) • Anti sperm cytotoxic antibodies (Microagglutinating and complement mediated cytotoxicity tests) • Anti ovarian cell antibodies (Indirect immunofluoroscence-ovarian tissue)

  12. Anti parathyroid antibodies (Indirect immunofluorescence-parathyroid tissue) • 38% Idiopathic hypoparathyroidism • 26% Idiopathic addison’s diseases • 12% Hashimoto’s thyroiditis • 6% Control group Blizzard RM. Clin. exp. Immunol. (1966) 1, 119-128. • Anti calcium sensor receptor antibodies (Anti CaSR antibodies. Activating; inhibitory) (Brown EM. Endocrinol Metab Clin North Am. 2009 June ; 38(2): 437-) • Anti pituitary antibodies

  13. Interferon and antibodies • Seven out of 50 patients after interferon treatment developed thyroid dysfunction (Hypothyroid: 5; Hyperthyroid: 2) (Chaudhry N et al. PAFMJ 2011.) (Chutto MA et al. JCPSP 2009.) • Antibodies after interferon treatment TPO (p=0.036); ANA (p=0.014) Chronic HCV infected patients (32/106; 30%) Interferon treatment (22/36; 61%) No treatment (12/32; 37.5%) increase in autoimmunity significant in males: p=<.04 (accepted for publication: Ahmad D et al. PAFMJ 2012;..)

  14. Autoantibodies in liver disease

  15. Autoimmune hepatitis • AFIP data (March 2010-March 2011) • Smooth muscle antibodies 397 38 • SLA 11 1 • LKM 307 3 • AMA 275 5 • Anti parietal cell antibodies (Ahmed D et al. Pakistan J of Pathology 2009; 20(3): 70-73)

  16. Anti pancreatic duct antibodies

  17. Autoimmune pancreatitis • IgG4 antibody levels • Anti pancreatic duct antibodies

  18. Anti parietal cell antibodies

  19. Anti parietal cell antibodies Atrophic gastritis & pernicious anemia (3 positive out of 46) • Anti intrinsic factor antibodies (0 positive out of 27) • 12 patients positive for anti intrinsic factor antibodies out of 78 vitamin B12 deficient patients (local study unpublished data)

  20. Anti islet cell antibodies

  21. Total Positive • Anti islet cell antibodies 10 0 1st degree relatives of IDDM • Anti insulin antibodies 1st degree relatives of IDDM Insulin resistance

  22. Anti adrenal antibodies • Addisons disease • 50% of idiopathic addison’s disease (Brown RM. Clin. exp. Immunol. (1967) 2, 19-30.) • 83% of primary addison’s disease positive for anti adrenal antibodies (IF) • 100% positive for anti 21-alpha hyroxylase antibodies in autoimmune addison’s disease (Betterle C et al.Endocrine Reviews 2002. 23(3):327–364) • Premature ovarian failure • 3.2%positive for anti adrenal antibodies

  23. Anti adrenal antibodies • APS type 1 13% • APS type 2 41% • APS type 4 5% • Isolated autoimmune adrenal disease 41% (Betterle C et al.Endocrine Reviews 2002. 23(3):327–364)

  24. Autoimmune polyendocrine syndrome, type 1. candidiasis-hypoparathyroidism-Addison's disease-syndrome, Autoimmune Polyglandular Syndrome I,[2] APECED, or APS-I Other disease associations are: • hypothyroidism • hypogonadism and infertility • vitiligo (depigmentation of the skin) • alopecia (baldness) • malabsorption • pernicious anemia • chronic active (autoimmune) hepatitis Autoimmune polyendocrine syndrome, type II.  autoimmune adrenal insufficiency autoimmune thyroid disease and/or type 1 autoimmune diabetes mellitus defines

  25. Conclusion • Auto antibodies remain the only test to identify autoimmune nature of endocrine diseases. • Auto antibodies may be tested using relatively simple laboratory techniques to help establish the diagnosis of relatively rare diseases.

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