W7 - 2ndary immunodeficiency & HIV Flashcards
Which is more common - 2ndary or primary immune deficiencies?
2ndary
Give examples (7) of 2ndary immune deficiencies. What is the commonest cause?
- infectious diseases: HIV
- environmental stress
- Age extremes: prematurity & old age
- Surgery and trauma, eg) splenectomy
- Immunosuppressive drugs
- Genetic + metabolic diseases
- Malnutrition (COMMONEST worldwide)
Name 4 clinical features of immune deficiencies
- Infections - severe, persistent, recurrent, unusual
- Autoimmune conditions (cytopaenias) & allergic disease
- Persistent inflammation
- Cancer (especially those virally associated EBV, HHV-8)
Name 4 classes of drugs that cause immune deficiencies. Give examples of each
- Small molecules
- Glucocorticoids & mineralocorticoids
- cytotoxic agents => methotrexate, mycophenolate, cyclophosphamide, azathioprine
- Calcineurin inhibitors => cyclosporine, tacrolimus
- anti-epileptic drugs => phenytoin, carbamazepine, levetiracetam
- DMARDs => sulphasalazine, leflunomide - JAK inhibitors => tofacitinib, ruxolitinib
- Biologic agents => anti-CD20 (rituximab)/anti-CD38, anti-TNFa (infliximab, etanercept)
- Cellular therapy => anti-CD19/BCMA Car-T cell therapy
Anti-TNF agents are linked to reactivation of ______________
TB
* hence why patients are screened for TB prior to starting anti-TNF
Name 2 anti-TNF alpha drugs
infliximab, etanercept
Name an anti-CD20 drug
Rituximab
B and plasma cell cancers can present with immune deficiency, out of which the most common immune deficiency is
antibody deficiency syndromes
Name 4 B cell lymphoproliferative disorders associated with immune deficiency
- Multiple myeloma (MM)
- Chronic lymphocytic leukaemia (CLL)
- Non Hodgkin’s lymphoma (NHL)
- Monoclonal gammopathy of uncertain significance
What is Good’s syndrome?
thymoma AND antibody deficiency
What is the B cell and T cell profile of someone with Good’s syndrome?
What sort of infections are they susceptible to?
What sort of autoimmune diseases are they susceptible to? Why do they form autoimmune diseases?
B cell absent, T cell absent in 50%
CMV PJ pneumonia, mucosal and cutaneous candida infections
Pure red cell aplasia, myasthenia gravis, Lichen planus => b/c they lack thymus for central selection of these T cells
Frontline investigations for immune deficiency
FISH for it:
F - FBC => Hb, neutrophil, lymphocyte, platelet count
I - Immunoglobulins => IgG, IgA, IgM, IgE
S - serum complement (C3, C4)
H - HIV test (18-80 yrs)
other chemistry tests:
- renal + liver profile
- calcium + bone profile
- total protein + albumin
- urine protein/Cr ratio
- serum protein electrophoresis (SPE)
- serum free light chains
Describe the use of serum protein electrophoresis (SPE) test
SPE separation of serum proteins by charge
Detection of discrete bands
monoclonal protein associated with => MM, WMG, NHL, MGUS
Con of SPE test
can miss free light chain disease - seen in 20% of MM
Second line investigations for immune deficiencies
- Check for vaccine antibody concentration => can also perform dynamic test where you vaccinate then proceed to check ab response
- Flow cytometry => analysis of lymphocyte subsets
Describe management (5) of secondary immune deficiency
- Treat underlying cause
- Advise on measures to reduce exposure to infection
- Immunisation against respiratory viruses/bacteria + vaccines to household contacts
- Education to treat bacterial infections promptly
- Prophylactic antibiotics for recurrent (>3/yr) bacterial infections
HIV - viral family, type of virus (RNA/DNA)
Lentivirus
double-stranded RNA virus
retrovirus
Describe how HIV enters cells
binds to CD4 and to co-receptor CCR5 or CXCR4
enters cell
replicates via a DNA intermediate
integrates into host genome
HIV DNA transcribed to viral mRNA => viral protein => packaging and release of mature virus
How many distinct lineages of HIV-1 do we have?
4 - M, N, O, P
MNO from chimpanzees, OP from gorillas
What baseline investigations (7) do you order for suspected HIV?
- FBC
- Renal, liver, bone, lipid profiles
- HbA1c
- Sexual health screen => RPRGU, Hep A, B, C serology
- Screen for latent TB
- Baseline CXR + ECG
- toxoplasma serology
What HIV specific tests (5) can you order?
- HIV viral load
- HIV genotype for ART drug resistance
- HIV tropism - to confirm co-receptor use in HIV patient who may be candidates for treatment with CCR5 antagonist
- HLA-B*5701 blood test => avoid prescribing Abacavir (NRTI) and risk of severe hypersensitivity in those with this allele (8% of NW London population)
- Analysis of T cell counts => CD4 count, CD4/CD8 ratio
When does viral load set point stabilise? What does it signify?
3-6 months after initial infection
viral load set point correlates with long term outcome (i.e. progression to symptomatic HIV)
Name 5 classes of ART drugs + give examples
- Reverse transcriptase inhibitors -> A) NRTI (EMTRICITABINE, tenofovir, abacavir), B) NNRTIs (Efavirenz)
- Boosted protease inhibitors (ritonavir-boosted PI, such as ritonavir + atazanavir)
- Integrase inhibitors (Dolutegravir DTG, Raltegravir, RTG, EVG)
- CCR5 antagonist (Maraviroc)
- Fusion inhibitors (T20; rarely used)
Do not give ART to HIV+ patient if CD4 T cell count is maintained at adequate levels - T or F
FALSE - Offer ART at diagnosis of HIV-1 infection, irrespective of CD4 T cell count
What is PReP and who is it for?
Pre-exposure prophylaxis (PReP) to reduce risk of acquisition of HIV-1 for those at higher risk due to sexual activity or drugs
What is a typical standard ART regimen?
2 NRTI + 1 NNRTI
OR
2NRTI + 1 integrase inhibitor
What is the main reason why HIV-1 patients change HIV therapy?
Drug toxicity (rather than virological failure)
How will ART affect the patient’s viral load?
It can prevent new cells from becoming infected but cannot eliminate infection once HIV-1 has integrated into host DNA (roughly 72hr)
What happens to blood viral load if patient stops taking ART?
HIV will be detected in blood 2-3 weeks later
If patient with HIV-1 infection start ART before significant immune damage, individual will have a similar life expectancy to age and sex matched seronegative controls - T or F?
True
What sort of monitoring (5) does HIV+ patient on ART require?
- Check for drug compliance + side effects
- Regular HIV-1 viral load
- CD4 T cell count (more than 350 cells/ul)
- Monitor liver, renal, bone and lipid toxicity
- Assess CVD and osteoporosis risk
Name 4 methods of HIV prevention
- Education
- Condoms
- Male circumcision
- ART (& PrEp)
Describe how the Berlin & London HIV patients were cured
Allogeneic HSC transplant from CCRdelta32 HLA matched donors => virus cannot infect these cells
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
E
A 57-year-old male is referred to the Chest clinic with recurrent chest infections, requiring antibiotic therapy. Past medical history reveal lichen planus and a history of surgery for an anterior mediastinal mass 4 year previously. Physical examination show nail candidiasis, sternotomy scar and bi-basal crepitations. A HRCT chest scan shows extensive bronchiectasis.
Immune investigation are as follows
IgG – 3.1g/L (ref interval 6.4-16.0g/L)
IgA – 0.4g/L (ref interval 0.8-3.4g/L)
IgM – 0.2g/L (ref interval 0.5-2.0g/L)
IgE 500IU/ml (reference interval 3-120IU/ml)
B cell count 10cell/ul ( ref interval 100-500)
What is the most likely diagnosis?
A) Partial antibody deficiency syndrome
B) Common variable immune deficiency
C) High grade B cell Mediastinal Lymphoma
D) Thymoma with antibody deficiency/Good’s syndrome
E) Hyper IgE syndrome
D
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
B
Which of the following statements are true about HIV-1 infection
A) Reverse transcription is associated with few errors in copying HIV-1 RNA template
B) Preferred option to commence ART in the UK is dual combination therapy containing an integrase inhibitor and NRTI
C) HLA-B*5701 blood test is used to prevent hypersensitivity reaction with protease inhibitors
D) Residual immune activation is commonly seen in patients on suppressive ART regimens
E) HIV-1 serology point care tests have similar diagnostic performance to 4th generation combined p24antigen/antibody tests
D
In an HIV patient, the risk of which infections increases at each CD4 T cell count:
- 500
- 400
- 300
- 200
- 100
- 500 = bacterial skin infections, herpes simplex, Zoster. Oral, skin fungal infections
- 400 = Kaposi’s sarcoma
- 300 = Hairy leukoplakia, tuberculosis
- 200 = PCP, cryptococcis, toxoplasmosis
- 100 = CMV, lymphoma
Describe 4th generation combined HIV antigen/antibody tests vs rapid point of care HIV tests vs HIV RNA tests
4th generation = detect infection 1 month POST acquisition
rapid point = result ready within 20 mins but LESS SENSITIVE than 4th generation
HIV RNA tests => where serological tests are negative but high clinical suspicion of acute HIV
Name 3 forces that drive diversity in an HIV infection
- Error prone nature of HIV RT
- Short generation time of viral cycle
- Length of infection
