HIV infection Flashcards
common causes of secondary immune deficiency
malnutrition - commonest cause worldwide esp protein loss effects cell mediated immunity
measles
TB
HIV - residual immune dysfunction despite ART (immune inflammation or increased markers of cellular or solbule markers of immune activation) -> increased risk of heart, lung, liver disease
Covid
how is measles a cause of secondary immune deficiency
immune defect lasts months to years,
implicated in increased morbidity and mortality due to secondary bacterial infection or diarrhoea.
Important in L or middle income countries.
TB and secondary immune deficiency
associated with depressed cell mediated immune response
picked up by failure to detect +ve mantoux test, or failure of inf-gamma release on ag specific assay used
as treat TB - immune response can reconstitute (immune re-constitution) - immune response wakes up and see other infections that patient has - and mounts inflammatory response
covid and secondary immune deficiencies
all things that make disease more severe
, virus, drugs and present of co-morbidities (renal disease and DM)
drugs as a cause of immune deficiency
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
steroids as a cause of secondary immune deficiency
Prednisolone - >10mg/day -> increased rate of Ab loss.
Higher dose -> increase susceptibility to infetcions
cytotoxic drugs as a cause of secondary immune deficiency
kill rapidly turning over cells inc immune cells
methotrexate, mycophenolate -> antibody deficiency
cyclophosphamide and azathioprine -> antibody and cellular def
calcineurin inhibitors and secondary immune deficiency
cellular immune deficiency
target dendritic cell, cd4 podicular dysfunction
will have knock on effect to respond to vaccine
antiepileptic drugs and secondary immune deficiency
phenytoin, carbamazepine, levetiracetam
Ab deficiency
DMARD and secondary immune deficiency
(sulphasalazine, leflunomide, methotrexate)
Ab immune deficiency
Jak inhibitors and secondary immuen deficiency
Can cause Ab deficiency.
Involved on reactivation of herpes zoster
biologic agents causing immune deficiency
anti-CD20/CD38/BCMA monoclonal antibodies
anti-TNF-α protein and receptor antagonists
Anti-CD20 – rituximab – increase the risk of Ab deficiency -> secondary bacterial and viral infection eg rhinovirus/norovirus where Ab are important in their control
B cells are APC to T cells – so risk of fungal infections for rituximab – so start on PCP prophylaxis
Agents targeting end stage of B cell maturation eg Anti-CD38 and anti-BCMA therapy will be found to be associated with increased risk of infection. Used in multiple myeloma rx
cellular therapy effect on immune dysfunction
anti-CD19/BCMA CAR-T cell therapy
give rise to B cell aplasia -> sig increased risk of invasive bacterial infection
anti CD19 CAR T cell therapy - associated with sig infection
use preventative than Ig infusion
rituximab and immune deficiency
Antibody deficiency and bacterial/viral/fungal infections are observed with anti-CD20 agents such as rituximab: ? Anti-CD38 and anti-BCMA therapy .
Risk of infection increased with repeated courses of rituximab and** in patient with a history of B cell malignancy (chemotherapy) and ANCA-related vasculitis (cyclophosphamide) .**
anti-TNF agents and immune deficiency
risk of activation of latent TB
have to screen pts for latent TB - put on preventative anti-TB agents
haematological cancers and immune deficiency
B and plasma cell cancers can present with immune deficiency
chemo, radio and biologic agents -> loss of immune cells and immune deficiency
what are the B cell lymphoproliferative disorders associated with immune deficiency
Multiple myeloma
Chronic lymphocytic leukaemia
Non Hodgkin’s lymphoma
Monoclonal gammopathy of uncertain significance – benign condition that can progress to B cell cancer.
what is Good’s syndrome
thymoma and ab deficiency :
Combined T and B cell (absent) defect
sinus, chest and GI infection
CMV PJP and muco-cutaneous candida
Autoimmune disease because thymus involved in central tolerance (Pure red cell aplasia, Myasthenia gravis, Lichen planus)
hx for secondary immune deficiency
clinical hx of infection
alarm sx for B cell cancers
hx of other illnesses - autoimmune cytopenia, bronchiectasis, rx for lymphoma/cancer/TB/hep B/C
Fx of infection/autoimmune disease/cancer
meds
vaccine hx - childhood, pneumococcal, influenza (household contacts should get flu vaccine)
how do you Ix for immune deficiency
FISH:
Full Blood count
* Hb < 10g/L
* neutrophil count
* lymphocyte count
* platelet count
Immunoglobulins (IgG, IgA, IgM, IgE )
Serum complement (C3, C4) - see whether unexplained lupus or complement deficiency
HIV test (18-80 years)
chemistry for immune deficiency
UE
LFT
Ca and bone profile
total protein and albumin - determine whether protein losing state
urine protein/creatine ratio - make sure not nephrotic syndrome
serum protein electrophoresis
serum free light chains
faecal calprotectin - make sure not IBD
serum immunoglublin test for immune deficiency
immunoglobulin profile may be helpful in dx:
Isolated reduction in IgG -> Protein loosing enteropathy or cumulative Prednisolone >10mg/day
Reduction in IgG and IgM -> Monitor for B cell neoplasm or History of exposure to rituximab
Reduction in IgG and IgA -> ? Primary antibody deficiency
serum protein electrophoresis for immune deficiency
separation of serum proteins by charge
Detection of discrete bands: monoclonal identified by immunofixation with labelled IgG, IgA, IgM anti-sera.
Monoclonal protein associated with multiple myeloma (IgG and IgA), WMG (IgM), NHL (IgM) and MGUS (IgM)
can miss free light chain disease - so need to measure them in B cell cancer work up
second line test to ix immune deficiency
- measure conc of vaccine ab - if Ig are low then want to know what the functional sig is
Tetanus vaccine – marker for protein Ag – how well T cell talk to B cell
Pneumovax – carb ag - T cell independent analysis of Ab production
if ab levels low - offer test immunisation with Pneumovax II and tetanus - ix immune function
failure to respond is part of diagnostic criteria for many primary immune deficiencies, and for IgG replacement for secondary ab def syndromes
2. analysis of lymphocyte subset using flow cytometry - quantify lymphocyte subsets
