Immunity and Diseases Scientific background to autoimmune diseases

1. Immunity and DiseasesScientific background to autoimmune diseases Dr Michael F. Ofori Noguchi Memorial Institute for Medical Research College of Health Sciences University of Ghana

2. Autoimmune diseases result when the immune system attacks the body's own organs, tissues and cells. • Physicians and scientists have identified a number of different autoimmune diseases. • Some are well known, • Others are less familiar,

3. Tolerance and Autoimmunity • The Immune system could go awry and instead of reacting only against foreign antigens, could focus its attack on SELF ANTIGENS • This can result in a number of chronic and acute diseases including • Rheumatoid Arthritis • Multiple screlosis • Lupus Erythematosis • Certain types of Diabetes

4. Types Of Autoimmune diseases • Physicians and scientists have identified more than 80 different autoimmune diseases. • Some are well known, • rheumatoid arthritis, • multiple sclerosis, • type 1 diabetes • systemic lupus; • others are less familiar, • autoimmune hepatitis, • Sjögren's syndrome • pemphigus

5. WHY THIS? • The results of the failure of the host’s humoral and cellular immune system to distinguish SELF from NON-SELF • This will result in the attack of self cells and organs by Auto-antibodies and self reactive T-cells.

6. WHAT IS AUTOIMMUNITY? • This is referred to the inappropriate response of the immune system against self components . • Autoimmune reactions can cause serious damage to cells and organs

7. Examples

8. Organ specific Autoimmune Diseases • Hashimoto’s Thyroiditis • Frequently seen in middle aged women • X’terised by infiltration of thyroid gland by lymphocytes, macrophages and plasma cells • The ensuing inflammatory response causes GOITER or visible enlargement of thyroid gland – a physiological response to hypothyroidism (decreased production of thyroid hormones • Hypothyroidism is caused when Abs are formed to a number of thyroid proteins including thyroglobulin and thyroid peroxidase – both involved in iodine uptake • Autoimmune hemolytic anaemia

9. Systemic Autoimmune Diseases Here the response is directed towards a broad range of targets and antigens and also involve a number of organs and tissues • Systemic Lupus erythematosus (SLE) • Appears in women b/n 20 and 40 years of age • Ratio of females to males is 10:1 • X’terised by fever, weakness, arthritis, skin rashes and kidney desfunction • It is more common in African American and Hisponic women than Caucasians • Reasons?

10. Multiple sclerosis • Attacks the CNS and causes neurological disabilities • IT could be mild such as numbness in limbs or severe such as paralysis or loss of vision • Genetic influence is important here • Risk is higher in women than men 2 - 3X higher • Rhematoid arthritis • Attacks the joints • Most often common in women b/n the ages of 40 – 60 • Main effect being the inflammation of the joints • But can also cause hemolytic, cardiavascular and respiratory systems

11. Economic Importance • The social and financial burdens imposed by these chronic, debilitating diseases include: • poor quality of life, • high health care costs • substantial loss of productivity • In addition, the majority of autoimmune diseases disproportionately affect women,

12. Why are women more susceptible than men to Autoimmunity?

13. Reasons put forward so far includes; • Differences in Antibody production • Females produces more Ab than males • They also mount more vigorous immune response than males • Sex hormones also play important role • Studies have shown that estrogen can stimulate auto-antibody production • Demonstrated in SLE-prone mice • Testosterone seems to be protective against several types of autoimmune diseases, eg.SLE, diabetes,MS etc • Ability of pregnant women to modify their immune system during pregnancy to keep the fetus • The presence of fetal cell in maternal circulation for decades – this can also lead to the development of autoimmune diseases

14. Major research Areas • Causes of Autoimmune Diseases • The Burden of Autoimmune Diseases • Diagnosis, Treatment and Prevention • Training, Education and Information

15. POSSIBLE CAUSES Of Autoimmune diseases Genetic, Environment, Infections etc • Recent reports have shown a marked association between 2-nonynoic acid, a cosmetic ingredient and primary biliary cirrhosis (PBC), a disease 9 times more likely to occur in women. • Other suspected triggers of Autoimmune diseases include • smoking, • bacterial & retroviral proteins, • hormone replacement therapy, • use of nail polish. • It’s thought that chemical degradation in the liver causes a loss of immune tolerance that predisposes Individuals to autoimmune diseases.

16. Research In Ghana • Study Conducted between 1983 and 1989 - 6yrs Period. • Korle Bu Teaching Hospital • They recorded 23 cases of Connective tissue disease during the period out of 4,507 admissions • Age ranged from 26 – 63 yrs (mean = 44yrs) • 16 (70%) were females • 11 had SLE • 8 had R.A • SLE 2.4 per thousand • RA. 1.8 per thousand • They then concluded that SLE and RA are NOT COMMON Affram RK and Neequaye AR, (1991). Systemic Lupus erythematosus and Other Rheumatic Disorders: Clinical Experience in Accra:, Ghana Medical Journal Vol 25:299-302

17. Other studies SLE is most prevalent in women of African Origin – This has been demonstrated in a number of studies • McCarthy et al 1995 • Symmons,1995, • Houcgberg,1985, • Siegel et al 1970

18. SLE IN AFRICANS • Population studies unavailable up to date • Most studies done are on case reports or series of reports of hospitalized patients. • Some of the countries in which these studies has taken place include: • South Africa, Zimbabwe, Ghana, Nigeria, Guinea, Cote D’ voire, Gabon, DR Congo, Senegal • From all these published reports, SLE appears to be RARE in Africa

19. SLE IN AFRICANS Cont’ • Recent Studies from South and Central African suggest SLE to be increased in these regions whilst that in West African remain to be RARE • This can be explained by the reportingBIAS

20. Treatment of Auto-immune Diseases • Current therapies include • Treatment with immunosuppressive drugs • Thymectomy and plasmapherisis for diseases involving immune complexes • TNF alpha Blockers • For controlling RA and Crohn’s disease • Treatment of human autoimmune diseases poses special challenges

21. Challenges • Use of Immunosuppressive drugs does not leave the other immune system Intact • Immuno suppressive drugs such as: • Corticosteriods, • Azathioprine • Crclophosphamide • are capable of depressing the immune response but also puts the patient at a greater risk of infection and development of cancers • Most current Therapies are not for cure but only reduces symptoms

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