SCID

SCID

1. • Types of primary immunodeficiencies

   • Antibody
   • Cellular, combined
   • Phagocyte
   • Complement
   • Malfunction of regulation
   • Syndromes with compromised DNA repair

2. Inheritance of immunodeficiency

   • X-linked recessive
     • common in males more than females

3. What is SCID

   • Severe Combined Immunodeficiency
     • highly susceptible to life-threatening infections
   • a rare condition
   • Caused by defects in any of several possible genes
     • Adenosine deaminase deficiency
       • ADA converts adenosine and deoxyadenosine to inosine and deoxyinosine
       • Accumulation of dATP
         • inhibition of ribonucleotide reductase
           • B and T cells unable to divide
   • fatal, usually within the first year of life
   • Cellular and Humoral Components
     • Cellular
       • Thymus not present
         • T cells will not mature
       • Thymus present but T cells are not produced
         • Thymus will shrink
     • Humoral
       • B cells affected from
         • The absence of T cells
         • cannot produce antibodies or cannot class switch

4. diagnosis of SCID

   • CBC + DBC
     • Leukopenia if below 3000 in children younger than 1 year
   • Total serum immunoglobulin (Ig) levels
     • IGM
   • Lymphocyte function
     • Mitogenic signals
   • Chest x-ray
     • thymus shadow

5. treatment and management of SCID

   • Protective management
     • Isolated bubble
   • IV Ig
   • Prophylaxis
   • Stopping live vaccinations
   • Hematopoietic cell transplant
     • First choice of treatment
   • Gene therapy
     • Not available for everyone
     • Very expensive
     • Limited studies done on it reducing its reliability
   • Enzyme replacement therapy ERT
     • Weekly IM
     • Might require continuous Ig therapy

6. Role of MHC (MAJOR Histocompatibility Complex) , HLA (Human Leukocyte Antigen)

   • Histocompatibility
     • Major Complex (MHC)
       • Cluster of genes >>> Glycoproteins
       • Discriminate self/ non-self
       • Ag presenting structures
       • Act as antigens in in-compatible recipient
     • Minor Antigen (miHA)
       • Cell-surface receptors of donated organs
       • Polymorphic proteins e.g. H-Y/ HA-2
       • A.A differences between donor & recipient
   • Classes of MHC Genes
     • Class I
     • Class II
     • Class III
   • Features of MHC
     • Highly Polymorphic
     • Co-dominant Expression
     • Low affinity, broad specificity
     • Low affinity, broad specificity

7. Tests for Compatibility

   • Blood Typing
   • Tissue Typing
     • Genomic typing: Allele specific PCR/Sequencing
   • Cross-Matching
     • Complement-dependent Cytotoxicity
     • Flow Cytometry
     • Mixed Lymphocyte Culture
     • Panel Reactive Antibody
   • Others
     • ELISA
     • Limiting Dilution Analysis
     • Direct Cytotoxicity Assay

8. Donor guidelines

   • Medical suitability
   • Donor eligibility
   • Donor evaluation
   • pathogens that may be transmitted by the graft
   • Informed consent
   • Preoperative assessment

9. GVHD

   • Allograft
   • Definition
   • types
     • acute GVHD
     • Chronic GVHD

10. Post-transplant care recommendations

    • Long term screening
      • Weekly visits for one month
      • Biweekly visits in the next wo months
      • Monthly visit for six two twelve months
      • Vital signs, body weight and height in every visit
    • Vaccination
      • vaccines should be offered from about 12 months post HSCT
      • No live vaccines are given until at least 2 years post HCT
      • Same as defaulters schedule
      • patient’s surrounding family must be completely immunised
    • Screening for chronic GVHD
      • allogeneic hematopoietic stem cell transplant should be monitored for chronic GVHD

11. Consent in organ donation

    • Informed consent
    • Required request
    • Presumed consent

12. Organ donation in Islam

    • living donor
      • it is allowed to donate unless
        • donor’s life is put at risk
          • vital organs like the heart are not allowed to be donated
        • physically cannot tolerate the operation
    • Dead donor