IFN-y and IL-12 deficiencies Flashcards
Why was it unusual for a women with IFN-y deficiency to present with disseminated TB?
Because deficiencies in the IFN-y/ IL-12 axis mostly associated with non-TB mycobacterial infections.
What four drugs are standard therapy for TB?
isoniazid, rafampicin
ethambutol and pyrazinamide.
Where did TB disseminate to in this IFN-y deficient patient?
to vertebrae (back), forearman/ palm discharging sinus. And effuion in pleual cavity. kidney with cystic change.
What tests might you check for in this women case?
HIV
Immunoglobulin levels
CD4 T cell
Lymphocyte proliferation to OKT3.
What is the IFN-y/IL-12 axis.
APC produces IL-12 that binds IL12a/B receptor.
Stimulates T cell to produce IFN-y that can bind to APC IFN-yR1 /2.
What is each IFN-y receptor made up of?
IFN-yR1(a) with JAK1 bound, and IFNyR2(B) with JAK-2 bound.
Dimerization of 2x of these subunits on IFNy binding.
What JAK/STAT signalling occurs downstream of IFNy binding?
JAK1 and JAK2 and STAT1 dimerisation.
What infections are people with IFNy/IL12 axis deficiencies susceptible to?
non-TB mycobacteria and (non-typhi) Salmonella.
Severe viral infections like Herpes, as well as other intracellular histpolasmosis and toxoplasmosis.
What deficiencies in these axis has been identified?
IFNyR1/2
STAT1
IL-12p40
IL-12RB1.
What is the prognosis like for IFN-yR1 deficiency?
Early presentation in young children and often death without a bone marrow transplant.
What is the prognosis like for IL-12RB1 deficiency?
Better prognosis than IFNyR1 deficiency.
Successfully treated with agents (IFN-y) and don’t require BMT.
Outcomes improves with age and acquired immunity/
What other cause could mimic IFN-y deficiency?
autoantibodies produced against IFN-y.
What was women with IFNy deficiency treated with?
Subcutaneous IFNy therapy.
