Secondary immune deficiencies and HIV-1 infection

Question 1

What are causes of secondary immune deficiencies?

Answer 1

Malnutrition

Infectious Diseases e.g. HIV

Environmental stress

Age Extremes: Prematurity and old age

Surgery and trauma splenectomy

Immunosuppressive drugs

Genetic and metabolic diseases

Question 2

What are signs and symptoms of secondary immune deficiencies?

Answer 2

Infections: Severe, persistent, recurrent, unusual

Autoimmune conditions (cytopaenias) and allergic disease

Persistent inflammation

Cancer (viral associated EBV, HHV-8)

Question 3

Which drugs can cause immune deficiencies?

Answer 3

Small molecules:

• Glucocorticoids and mineralocorticoids
• Cytotoxic agents: Methotrexate, mycophenolate, cyclophosphamide
• and azathioprine.
• Calcineurin inhibitors: Cyclosporine and tacrolimus
• Antiepileptic drugs (phenytoin, carbamazepine, levetiracetam)
• DMARD (sulphasalazine, leflunomide)

JAK inhibitors:

• Tofacitinib
• Upadacitinib
• Ruxolitinib

Question 4

Which drug class can cause TB reoccurance?

Answer 4

Anti-TNF agents

Question 5

Which cancers are common with secondary immune deficiencies?

Answer 5

B and plasma cell cancers can present with immune deficiency (antibody deficiency syndromes are most common).

Chemotherapy, biological agents, and radiotherapy can leads to loss of immune cells and immune deficiency.

Question 6

Which specific B-cell lymphoproliferative disorders can arise from secondary immune deficiencies?

Answer 6

Multiple myeloma

Chronic lymphocytic leukaemia

Non Hodgkin’s lymphoma

Monoclonal gammopathy of uncertain significance

Question 7

What is Good’s syndrome?

Answer 7

Thymoma and antibody deficiency

Combined T and B cell (absent) defect

CMV PJP and muco-cutaneous candida

Autoimmune disease (Pure red cell aplasia, Myasthenia gravis, Lichen planus)

Question 8

What are appropriate investigations for secondary immune deficiencies?

Answer 8

Full Blood count

Hb < 10g/L

Neutrophil count

Lymphocyte count

Platelet count

Immunoglobulins (IgG, IgA, IgM, IgE )

Serum complement (C3, C4)

HIV test (18-80 years)

Strategy will pick up to 85% of all immune defects

Question 9

What is serum protein electrophoresis?

Answer 9

SPE separation of serum proteins by charge

Detection of discrete bands: monoclonal identified by immunofixation with labelled IgG, IgA, IgM anti-sera

SPE can miss free light chain disease which is seen 20% multiple myeloma cases): hence measurement of free light chains is essential for work up of B cell LPD.

Question 10

What are second line investigations for secondary immune deficiencies?

Answer 10

Measure concentration of vaccine antibodies:

• Tetanus toxoid: Protein antigen
• Pneumovax vaccine: Carbohydrate antigen ( all 23 serotypes or to individual pneumococcal serotypes)

Question 11

What are third line investigations for secondary immune deficiencies?

Answer 11

Analysis of naïve and memory T and B cell subsets

Assessment of IgG subclasses

Determination of anti-cytokine and complement antibodies:

• Anti-Type 1 interferon antibodies (IFN-α and IFN-ω) in SARS-CoV-2 infection
• Anti Type 2 interferon antibodies (IFN-γ) in disseminated NTM infection
• Anti-GM-CSF antibodies disseminated in cryptococcal infection
• Anti-C1 inhibitor antibodies and acquired late onset angioedema ( B cell LPD and SLE)

Genetics (whole exome or whole genome sequencing in cases where it is difficult to work if you are dealing with primary or secondary immune defect

Question 12

What is the management of secondary immune deficiencies?

Answer 12

Treat underlying cause

Advise on measures to reduce exposure to infection

Immunisation against respiratory viruses and bacteria and offer vaccines to household contacts

Education to treat bacterial infections promptly: May require higher and longer therapies courses (co-amoxiclav 625mg TDS for 10-14 days rather then 375mg for 5-7 days)

Prophylactic antibiotics for confirmed recurrent bacterial infection