2. Secondary immune deficiences and HIV-1 infection

Question 1

What diverse clinical features do immune deficiencies exhibit?

Answer 1

Infections, autoimmune conditions and allergic disease, persistent …, cancers

Question 2

Common causes of secondary immune deficiencies

Answer 2

Malnutrition, measles, mycobacterium tuberculosis, HIV infection, SARS-CoV-2

Question 3

Commonest cause of secondary immune deficiencies?

Answer 3

malnutrition

Question 4

Immune defect from measles lasts how long?

Answer 4

Months to years, increased morbidity and mortality

Question 5

What is mycobacterium tuberculosis?

Answer 5

…

Question 6

What is HIV?

Answer 6

…

Question 7

What drugs cause immune deficiency?

Answer 7

• Small molecules: glucocorticoids and mineralocortioids

- cytotoxic agents: methotrexate, mycophenolate, cyclophosphamide and azathioprine ….

Question 8

Can biologics and cellular therapies cause immune deficiency?

Answer 8

Yes, increasingly recognised as a cause

Question 9

Biologic agents:

Answer 9

anti-CD20 monoclonals…

Question 10

Cellular therapies:

Answer 10

anti-CD19/BCMA CAR-T cell therapy

Question 11

Haematological cancers that can present with immune deficiency?

Answer 11

B and plasma cell cancers?

B cell: multiple myeloma, chrinic lymphocytic leukaemia, non-hodgkin’s lymphoma, monoclonal gammopathy of uncerain significance.

Goods’ syndrome ….

Question 12

Consider FISH for an immunodeficiency! What does this consist of?

Answer 12

Full blood count, immunoglobulin (IgG, IgA, IgM, IgE), serum complement (C3, C4), HIV test (18 - 80 years).

Strategy will pick up 85% of all immune defects

Question 13

Front line investigations for immune deficiency

Answer 13

Chemistry: renal and liver profile; calcium and bone profile; …

Question 14

What does isolated reduction in IgG suggest?

Answer 14

Protein losing enteropathy. Prednisolone 10mg/day

Question 15

What does reduction in IgG and IgM suggest?

Answer 15

Monitor for B cell neoplasm, history of exposu….

Question 16

What is SPE?

Answer 16

Serum protein electrophoresis.

First line test. Detection of discrete bands: monoclonal identidfied by immunofixation with labelled I…

Question 17

What are second line tests to investigate immune deficiencies?

Answer 17

Tetanus toxoid (protein antigen) might be reduced.

Pneumova vacine (carbohydrate antigen)

If vaccine antibody levels low, offer test immunisation with pneumovax II and tetanus to investigate immune function

Can also do analysis of lymphocyte … cytometry

Question 18

What are third line investigations for immune deficienes

Answer 18

Analysis of naive and memory T and B cell subsets; assessment of igG subclasses; determination of anti-cytokine and complement antibodies: anti-type 1 interferon, anti-type 2 … etc etc.

Question 19

Management of secondary immune deficiencies

Answer 19

Treat underlying cause, advice to reduce exposure, immunisation and vaccines, education to treat bacterial infections, prophylactic ABx

Question 20

Five characteristic features of the immunology of IV-1 infection

Answer 20

CD4 T cell depletion, chronic immune activation, impairment of CD4 and CD8 T cell function, disruption of lymph node architecture and impaired ability to generate protective T and B cell immune responses, loss of antigen-specific humoral immune responses

Question 21

How to diagnose HIV-1?

Answer 21

4th gen combined HIV-1 antigen/antibody tests will detect infection 1 month post acquisition of infection, assay detect p24 antigen, gp41 from HIV-1, group O, gp160 …….

Question 22

Evaluation or management of HIV-1?

Answer 22

1. Confirm what they know. 2. co-morbidities. 3. sexual health history, up-to-date vaccines, cervical screen. 4. discuss partner notification and u = undetectable -> untransmissable. 5. screen for factors that may impair adherence to ART (psychological issues, alcohol/drug dependency, accommodation, social support)

Question 23

HIV-1 specific tests

Answer 23

viral load, genotype … etc

Question 24

Anti-retroviral therapy available in the UK

Answer 24

Revers transc….

Question 25

use of ART

Answer 25

test and treat; treat to prevent infection; prophylaxis

Question 26

A 65 year-old male with a history of steroid dependent asthma, hypertension, Type 2 Diabetes Mellitus and osteoporosis presents with recurrent chest, sinus, and skin infections. Past medical history of chemotherapy for follicular lymphoma and he has recently completed a 2 year maintenance therapy of 3 monthly rituximab. Current oral medication includes Prednisolone 5mg OD, Losartan 50mg OD, metformin500mg BD, alendronic acid 70mg weekly.   Serum immunoglobulins are as follows IgG – 3.9g/L (ref interval 6.4-16.0g/L) IgA – 0.9g/L (ref interval 0.8-3.4g/L) IgM – 0.1g/L (ref interval 0.5-2.0g/L) IgE 200IU/ml (reference interval 3-120IU/ml) ``` Which of the following medication are most likely to have cause antibody deficiency A) Metformin B) Losartan C) Prednisolone D) Alendronic Acid E) Rituximab ```

Answer 26

Rituximab (oral prednisolone is less than 10mg)

Question 27

What is Good's Syndrome?

Answer 27

...

Question 28

Question 3 Which of the following condition are more likely to present in patients with a CD4 T cell counts of more than 350cells/ul A) CMV retinitis, Toxoplasma encephalitis, visceral Kaposi sarcoma B) Herpes zoster, Pulmonary Tuberculosis, Pneumococcal pneumonia C) Pneumocystis jirovecci pneumonia, disseminated MAC, ITP D) EBV CNS lymphoma, oral candida, cryptococcal meningitis E) Cutaneous Kaposi sarcoma, disseminated MAC, HSV infection

Answer 28

B?