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
IU/ml High
IU/ml Very high
>1000 IU/ml Extremely high
(103 positive out of 248. One year local unpublished data)
Euthyroid
Hyperthyroid
Hypothyroid
Total
IU/ml 2 7 16
IU/ml 6 4 17
>1000 IU/ml 5 1

7. Anti thyroid peroxidase antibodies
< 30 IU/ml Normal
IU/ml High
>300 IU/ml Very high
(109 positive out of 496. One year local data unpublished)
Euthyroid
Hyperthyroid
Hypothyroid
Total
IU/ml 5 - 10
>300 IU/ml 4 1 6 11

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); )
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); )

10. Pregnancy loss Anti cardiolipin antibodies IgG, IgA, IgM
Anti beta-2 glycoprotien 1 antibodies
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,
Anti calcium sensor receptor antibodies
(Anti CaSR antibodies. Activating; inhibitory)
(Brown EM. Endocrinol Metab Clin North Am 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
Antibody
Disease Association
Comments
Mitochondrial antibody
Primary biliary cirrhosis
>95%
Smooth muscle antibody
Autoimmune hepatitis
70%
30%
LKM
Drug induced hepatitis
Uncommon but specific antibody
ANA

16. Autoimmune hepatitis AFIP data (March 2010-March 2011)
Smooth muscle antibodies
SLA
LKM
AMA
Anti parietal cell antibodies
(Ahmed D et al. Pakistan J of Pathology 2009; 20(3): 70-73)

17. Anti pancreatic duct antibodies

18. Autoimmune pancreatitis
IgG4 antibody levels
Anti pancreatic duct antibodies

19. Anti parietal cell antibodies

20. 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)

21. Anti islet cell antibodies

22. Total Positive
Anti islet cell antibodies
1st degree relatives of IDDM
Anti insulin antibodies
Insulin resistance

23. Anti adrenal antibodies
Addisons disease
50% of idiopathic addison’s disease
(Brown RM. Clin. exp. Immunol. (1967) 2, )
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 (3):327–364)
Premature ovarian failure
3.2%positive for anti adrenal antibodies

24. Anti adrenal antibodies
APS type %
APS type %
APS type 4 5%
Isolated autoimmune adrenal disease 41%
(Betterle C et al.Endocrine Reviews (3):327–364)

25. 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

26. 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.