IMMUNO: Secondary immune deficiencies and HIV infection Flashcards
What are the causes of immune deficiencies?
- Infections
- AI and allergic disease
- Persistent inflammation
- Cancer
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Which childhood infection can cause secondary immune deficiency?
Measles - immune defect lasts from months to years
What are the common causes of secondary immune deficiencies?
- Malnutrition
- Measles
- TB
- HIV
- SARS-CoV-2
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What are the drug causes of immune deficiencies?
- Small molecules e.g. steroids, methotrexate/azathioprine, phenytoin, tacrolimus, DMARD
- JAK inhibitors e.g. -tinibs
- Biologic and cellular therapies e.g. anti-CD20, CAR-T cell therapies
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Give two examples of biologic agents/cellular therapies. When is risk of immunodeficiency from these greatest? What are anti-TNF agents linkes to in terms of infection?
- Biologics agents: anti-CD20/CD38/BCMA monoclonals, anti-TNF-α protein and receptor antagonists
- Cellular therapy: anti-CD19/BCMA CAR-T cell therapy
Risk: increases with repeated courses AND in patients with B cell malignancy and vasculitis
Anti-TNF: liked to TB reactivation
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Which B cell lymphoproliferative disorders are most associated with immune deficiency? (4)
- MM
- CLL
- NHL
- MGUS
What is the triad of Goods’ syndrome and what are the consequences of its immunodeficiency disorder?
TRIAD
- thymoma
- immunodeficiency
- hypogammaglobulinemia
- B and T cells absent
- CMV/ PJP / muco-cutaneous candida infections
- AI disease e.g. pure red cell aplasia, MG, lichen planus
Which haematological cancers cause immunideficiency and how?
B and plasma cell cancers as well as their associated treatments.
How do you evaluate secondary immune deficiency?
- Infection history, unusual childhood complications of illness, reaction to vaccines, loss of schooling
- PMH of other illness e.g. lymphoma, bronchiectasis, lymphoma/cancers, TB, hep B/C.
- FH of infection/AI/cancer
- Medication history
- Vaccine history e.g childhood, pneumococcal, flu vaccines
How do you ‘FISH’ for immunodeficiency? What % of IDs will be picked up this way?
- FBC - Hb <10g/L, neutrophil, lymphocyte, platelet counts
- Immunoglobulins (IgG, IgA, IgM, IgE)
- Serum complement (C3, C4) - immune complex disease or lupus
- HIV test (18-80years)
This will pick up 85% of immune defects
What are the other first line investigations for immunodeficiency after FISH?
renal and liver
calcium and bone
total protein and albumin
urine protein/Cr ratio
serum protein electrophoresis
serum free light chains
What clinical situations can cause reduction in
- IgG only
- IgG and IgM
- IgG and IgA
IgG - protein losing enteropathy, prednisolone >10mg/day
IgG and IgM - B cell neoplasm, rituximab
IgG and IgA - primary antibody deficiency
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Which vaccine related tests can be used later in the testing process for immune deficiencies? What is the management if these are deranged?
Tetanus toxoid- protein antigen detection
Pneumovax vaccine - carbohydrate antigen detection (for all 23 serotypes of to individual pneumococcal serotypes).
If low… offer Pneumovax II and tetanus immunisation to test immune function. Failure to respond to this is a criteria for receipt of IgG replacement therapy for secondary antibody deficiency syndromes.
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How is serum protein electrophoresis useful in immunodeficiency diagnosis? What can be missed on SPE?
- Serum proteins are separated by charge. Discrete bands are formed for each immunoglobulin as they bind by immunofixation
- Monoclonal proteins can indicate MGUS, MM etc.
- SPE can miss free light chain disease (seen in 20% of MM) so must measure these separately
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What are monoclonal protein bands associated with on SPE?
If monoclonal proteins are found this can be associated with:
- MM,
- WMG (Waldenström Macroglobulinemia),
- NHL,
- MGUS
What is the virology of HIV?
- Binds to CD4 and then cheomokine co-receptor CCR5 or CXCR4
- Replicates via DNA intermediate
- Integrates into host genome
- HIV DN Atranscribed to viral mRNA
- Viral RNA translates to viral proteins
- Packaging and release of mature virus
How can lymphocyte subsets be investigated in suspected immunodeficiency?
Flow cytometry
Gate for specific surface antigens e.g. CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD56+CD16+ NK cells, CD19+ B cells.
Which complex tests can be used for diagnosis of immune deficiencies (third line)?
NTM = non-tuberculous myobaceria
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What is the management of secondary immune deficiency?
- treat cause
- advise exposure reduction
- immunisation of patient and household contacts
- education to treat bacterial infection promptly (excluded from antimicrobial stewardship rules) e.g. co-amoxiclav 625mg TDS for 10-14 days, rather than 375mg for 5-7 days
- prophylactc antibiotics for confirmed recurrent bacterial infection
What are the indications for secondary antibody deficiency syndrome IgG replacement?
Unreversable hypogammaglobinaemia
OR
Hypogammaglobinaemia associated with treatment/post-treatmnet/cancer
AND
- Recurrent infections despite continuous abx for 6 months
- IgG <4g/L
- Failure of vaccine response to pneumococcal/other polysaccharice vaccine
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