Secondary Immunodeficiency

Question 1

What are patients who have had a splenectomy at risk of?

How are these patients managed?

Answer 1

Risk of overwhelming infection from encapsulated bacteria

Management:

• vaccination
• prophylactic antibiotics i.e. life-long penicillin

Question 2

Why can bronchiectasis be associated with increased risk of infection?

Answer 2

Dilated airways leads to decreased clearance of mucus i.e. ideal growth environment for bacteria

Therefore need to consider if bronchiectasis is the cause of the current infections or if it is secondary ID

Question 3

Why can being morbidly obese increase the risk of infections?

Answer 3

Fat secretes pro-inflammatory cytokines

Increased weight causes decreased flattening of the diaphragm which leads to decreased ability to breath properly and clearing of lungs i.e. increased risk of resp infection

Question 4

What are the 2 main haematological malignancy can cause ID?

Answer 4

Chronic lymphocytic leukaemia (CLL)

Multiple myeloma

NOTE:
-any myeloid or lymphoid malignancy could affect the immune system due to being a space occupying lesion so decreases the space available for immune cell production

Question 5

What are the ways haematological malignancies can effect normal B cell production?

Answer 5

Bone marrow failure
-infiltrate by malignant cells

LN effacement
-loss of site for TC and BC interaction

Medication/chemo
-can target plasma cells/ BC/ TCs

Loss of Ig through kidney

• free light chains clog up kidney and make it leaky
• Monoclonality can occur

Question 6

How can an electrophoresis be used to see if ID secondary to malginancy?

Answer 6

Electrophoretic strip will show loss of wide range of Ig

Gamma-globulin spike seen due to all Ig running at same molecular weight very little after the spike due to no other forms of Ig being present

Question 7

What is common causes of chronic neutropenia?

Answer 7

Drug-induced i.e. chemotherapy
-lowest neutrophil count 10 days post treatment

Autoimmunity i.e. anti neutrophil antibodies

Bone marrow failure

Sequestration in spleen

Anti-GM-CSF antibodies

Question 8

What are the consequences of neutropenia?

What should be given to neutropenic patients?

Answer 8

At risk of:

• neutropenic sepsis
• invasive extracellular bacterial infection
• invasive fungal infections i.e. candida + aspergillis

Need to give G-CSF to try and boost neutrophil levels and mitigate the risk of neutropenic sepsis

Question 9

What is Rituximab and what is its function?

Which cells will it target and which will it leave untouched?

Answer 9

Anti-CD20 monoclonal antibody
Fab domain= binds to the CD20 protein on surface of all B cells
Fc domain= interacts with Fc receptors which leads to:
-activation of complement
-induce antibody dependent cellular toxicity

THEREFORE: can induce BC aplasia w/i 1 week ang HYPOGAMMAGLOBULINAEMIA

Target= peripheral BC in spleen or LN
Leave intouched= haemopoetic stem cells + plasma cells

Question 10

What are the management options for secondary immunodeficiency?

Answer 10

Vaccinate

Antibiotic prophylaxis
I.e. levofloxacin

Ig replacement

• blood product produced from 1000s of donors
• only contain IgG

Stop/treat causative process

Question 11

What are the criteria to qualify for Ig therapy in secondary antibody deficiency?

Answer 11

IgG <3g/L
Fail to respond to pneumococcal vaccination
Fail to get better on 6/12 months antibiotic prophlaxis
Underlying causes must be irreversible

Question 12

What are the different pharmacological methods of inhibiting the cytokine axes?

Answer 12

Monoclonal antibody blokcing cytokine i.e. anti-TNF-alpha

Soluble version of receptor i.e. cytokine binds to this receptor rather than cytokine receptor

Monoclonal Ab to block receptor

Mimics of natural antagonist to receptor

Small molecule inhibitors of signalling molecules

Question 13

What are the consequences of TNF-alpha in RA?

Answer 13

Endothelial activation-> causes inflammation

Positive feedbacl on inflammatory cytokine cascades

Systemic= sarcopenia/malaise/lipid profiles/atheroma

Causes cartilage destruction via MMPs

Causes bone erosion via oesteoclasts

Question 14

What drugs can inhibit TNF-alpha?

Answer 14

Infliximab
Monoclonal IgG which prevents TNF-alpha from binding to receptor

Entanercept
Soluble TNF receptor which leads to TNF-alpha binding to it preferentially

Question 15

What are the possible adverse effects of anti-TNF medication?
What should all patients be screened for before starting anti-TNF medication?

Answer 15

Can lead to re-activation of latent TB
TNF-alpha normally released from TH cells in the granuloma to maintain the granuloma
Therefore anti-TNF will lead to disruption in integrity of granuloma and reactivation

Screened for:

• latent TB
• hepatitis B
• hepatits C
• HIV-1

Question 16

What is the use of Tocilizumab?

Answer 16

Anti-IL-6 therapy which can be potential treatment for severe covid and cytokine release syndrome following CART therapy

Question 17

What are the risks associated with taking Tocilizumab?

Answer 17

Decreases CRP release i.e. can miss the normal characteristics of acute response

Infections w/o raised CRP

Diverticulosis

Skin + soft tissue infections

Question 18

How would an abscess formed when on tocilizumab look different to a normal abscess?

Answer 18

There would be no erythema or signs of inflammation due to blockage of IL-6

Question 19

What is atypical haemolytic uraemic syndrome?
How can it be treated?
What must be done before treatment is started?

Answer 19

Rare dysregulation of complement where there is uncontrolled deposition of complement on surface of RBC leading to haemolysis

TX= Eculizumab i.e. blocks C5 of complement so that TCC can’t form
-increased risk of meningococcal infections + gonococcal

Before TX:

• meningococcal vaccinations
• make sure doesnt have gonococcal infection