1. How much gammaglobulin ? INGID VII th Meeting Budapest, October 7, 2006 Rolf Gustafson

2. Ökad infektionsbenägenhet 1880sImmunotherapy von Behring, Kitasato 1950sSubstitution therapy Bruton 1980sImmunomodulation Imbach, Barandun Immunotherapy - a short history

3. Ökad infektionsbenägenhet Serum from immunized animals (mainly horses) 1895Diphtheria antiserum 1908Meningococcal antiserum 1925Streptococcal antitoxin Immunotherapy

4. Ökad infektionsbenägenhet 1933 Placental extracts Diphteria Scarlet fever Polio Measles 1935 Convalescent human serum Rheumatic fever Impetigo Measles Chicken pox Scarlet fever Immunotherapy

5. Ökad infektionsbenägenhet 1940 The US National Research Council asked Dr. Edwin Cohn to identify a stable blood derivate or substitute. 1941 The American Red Cross began collecting blood. A grant of 10,000 USD for large scale production of human albumin was given. Substitution therapy

6. Ökad infektionsbenägenhet By help of manipulating the: ethanol concentration temperature pH Separation of plasma proteins

7. Rolf Gustafson/Baxter Medical

10. Ökad infektionsbenägenhet WHO International Red Cross International Society of Transfusion (ISBT) Council of Europe European Union European Agency for the Evaluation of Medicinal Products (EMEA) FDA Statements, Directives & Resolutions

11. IgG Trace amounts of IgM & IgA Soluble CD4 & CD8 Soluble HLA What is gammaglobulin ?

12. Rolf Gustafson/Baxter Medical Half - life of IgG % Weeks

13. Ökad infektionsbenägenhet Gammaglobulin became available in the mid – 1940s and was used for preventing viral diseases like: Measles Hepatitis A Gammaglobulin

14. Bruton´s boy

15. Ökad infektionsbenägenhet …………. started as subcutaneous injections at monthly intervals Substitution therapy

16. Ökad infektionsbenägenhet 1950s - 1960s Medical Research Council in England Data from 176 patients 25 mg / kg / week50 mg / kg / week fewer deaths less cases of pneumonia IgG 1.2 – 2.6 g/LIgG 2.9 – 3.8 g/L Substitution therapy

17. Ökad infektionsbenägenhet Late 1980s consencus of giving 300 - 400 mg / kg / month IgG 4 – 5 g/L 1987 Roifman et al. reported that 600 mg / kg / month was better than 200 mg / kg / month IgG > 5 g / L Substitution therapy

18. Ökad infektionsbenägenhet 2006 Approved and recommended dose: 400 - 800 mg / kg / month Substitution therapy

19. Ökad infektionsbenägenhet Evaluation Clinical outcome Increasing IgG level Substitution therapy

20. Ökad infektionsbenägenhet Intravenous infusions Substitution therapy

21. Rolf Gustafson/Baxter Medical IVIG - IgG levels g/L Day

22. Ökad infektionsbenägenhet Subcutaneous infusions Substitution therapy

23. Rolf Gustafson/Baxter Medical SCIG - IgG levels g/L Days

24. Ökad infektionsbenägenhet Indications X-linked agammaglobulinemia (XLA) Common variable immunodeficiency (CVID) Severe combined immunodeficiency (SCID) Wiskott Aldrich syndrome (WAS) Substitution therapy

25. What about IgG subclass deficiences ? In selected patients with: IgG1 deficiency IgG2 deficiency IgG3 deficiency Substitution therapy

26. Rolf Gustafson/Baxter Medical Half - life of IgG3 % Days

27. Ökad infektionsbenägenhet What about selective IgA deficiency ? In selected adult patients with: at least 4 treatments with antibiotics / year Substitution therapy

28. Gammaglobulinbehandling Gustafson R, Gardulf A, Granert C, Hansen S, Hammarström L Prophylactic therapy for selective IgA deficiency. Lancet 1997;350:865 SCIG therapy in IgA deficiency IgG therapy:100 mg/kg/week Infections per year Before IgG therapy During IgG therapy 0 – 105 2 – 305 ≥ 4 100

29. Ökad infektionsbenägenhet What is the goal with patient education ? The goal is … that the patient becomes an active and encouraged part in the decision-making process and have the knowledge about self-care activities and behaviors that foster health and health-related quality of life instead of being a passive receiver of information. A. Gardulf, 2002 Patient training & education

30. Training & education should include knowledge & understanding of: primary antibody deficiencies aim and importance of IgG therapy infections & antibiotic treament systemic adverse reactions self-care and prevention behaviour changes self-infusion technique Home-therapy training program – the key to success