1. The use of Immunology
tests in clinical practice
Dr Charu Chopra
SpR Immunology
30th June 2010
2. Learning Objectives
5 clinical case histories, with lab test data. MRCP
part 2 style format questions
Complement
Acute antibodies
Cryoglobulins
Anti-nuclear antibodies
Immunoglobulins
3. Q1. A 19 year old man presents to A&E with
swelling of his lips and tongue. He is quite
anxious and short of breath. You establish that
his saturations are 100% on 20% oxygen and
there is no stridor. His blood pressure is 120/85
mmHg. He was given a single dose of 10 mg iv
chlorpheniramine and im adrenaline (0.5mg) by
the paramedics. There is no skin rash. His
father died many years ago after a sudden
collapse.
4. What one diagnostic test would you
perform?
A) Total immunoglobulins
B) Serum IgE levels
C) Mast cell tryptase
D) C1 inhibitor level and function
E) C3 and C4 levels
What is the diagnosis?
6. Hereditary Angioedema (HAE)
Prev 1 in 50,000 (USA)
Recurrent well circumscribed swellings affecting
skin, intestine and airway
NO urticaria
Mortality 20-30% in the past
Autosomal Dominant; C1 inh gene chromosome 11
Tests: C1 inhibitor level and function
9. Fig 1 Immunofluorescence with patient
serum applied to Ethanol fixed neutrophils
Q2. A 55 year old Caucasian man
presents with haemoptysis, shortness
of breath and malaise. He is a non
smoker and has had these symptoms
for 4 months during which he has
lost 6kg in weight.
What does the slide demonstrate?
A) Anti-nuclear antibodies
B) Anti-GBM antibodies
C) Macrophage Activation
Syndrome
D) C-ANCA positivity
E) None of the above
11. Q3 A 47 year old man (previous
IVDU) presents with a 2 year history
of joint pains, purpuric rash and
Raynaud’s phenomenon. His urine
dipstick is positive for protein + and
blood ++.
What test would be most likely to
yield a diagnosis?
A) Complement levels
B) Immunoglobulins
C)
Liver/kidney autoantibodies
D) Anti-nuclear antibody
E)
Cryoglobulins
12. Answer: E
What further tests would you do?
Answer: Viral hepatitis serology, rheumatoid
factor, C3/C4
13. Cryoglobulinaemia
Presence in the serum of one (monoclonal) or more
(mixed cryoglobulinaemia) immunoglobulins which
precipitate at temperatures< 37 C and redissolve on
warming
Symptoms: Skin
Joints
Kidneys
hyperviscosity
Igs deposition / complement activation/
vasculitis
14. Cryoglobulins
Type 1 monoclonal immunoglobulin:
Haematological malignancies (CLL, CML, NHL, MM,
Hodgkin’s, Waldenstrom’s)
Type 2 (mixed) monoclonal and polyclonal
components. Rheumatoid factor +
Type 3 (mixed) polyclonal immunmoglobulins.
Rheumatoid factor +
Type2/3 : HIV, Hep C/B, Sjogren’s, SLE, PAN,
Scleroderma, Anti phospholipid syndrome, Familial
15. Fig 2 Immunofluorescence with patient
serum applied to Hep 2 cells
Q4 What does this image
show?
What conditions are
associated with this
serological profile?
A) SLE
B) Drug induced Lupus
C) Rheumatoid arthritis
D) Infection
E) All of the above
17. Fig 3 Immunofluorescence to detect ds
DNA antibodies (Crithidia luciliae
kinetoplast)
ds DNA antibodies highly
specific for SLE
18. Q5. A 48 year old lady presents in outpatients
clinic with a history of chronic shortness of breath,
daily cough productive of pale coloured phlegm
and recurrent chest infections. There is no history
of haemoptysis. She has had 3 episodes of
pneumonia over the last 2 years, requiring
hospital admission. Sputum cultures from these
grew Streptococcus pneumoniae on one occasion and
Haemophilus influenzae on another. An HRCT scan
of her chest showed bilateral diffuse
bronchiectasis with evidence of a few granulomata
in both lung fields. She is a non-smoker. There is
no other significant medical history
19. Bloods:
IgG 3.5 g/L (6-16)
IgA 0.2 g/L (0.8-2)
IgM <0.17 g/L (0.5-2)
No paraprotein detected
Which diagnosis would be in keeping with these
clinical
and laboratory findings?
A) Tuberculosis
B) Sarcoidosis
C) Chronic Granulomatous Disease
D) X-linked Agammaglobulinaemia
E) None of the above
21. The differential diagnosis of
panhypogammaglobulinaemia
Lymphoproliferative Disease: check urine BJP, serum EL (? paraprotein),
serum free light chains, LDH/beta-2-microglobulin, Ca profile, ? bone
marrow biopsy
Drugs: steroids, cyclophosphamide, gold salts/ DMARDs, anti-epileptics
Protein losing states (enteropathy, nephrotic syndrome) - but usually just low
IgG
Hypercatabolism of Igs in sepsis
Common Variable Immune Deficiency (CVID)
Rare: genetic causes (Trisomy 8, Trisomy 21, metabolic disease, myotonic
dystrophy, other PIDs)
Rare: Congenital infections (congenital Rubella/CMV/Toxo/EBV)
22. The immunoglobulins are repeated and are
found to be accurate values. The patient has
mild splenomegaly on examination.
How do you explain this patient’s signs and
symptoms?
23. CVID
Other clinical manifestations: hepatospelnomegaly,
granulomatous disease, anaemia, diarrhoea (?
giardiasis), arthralgia (?mycoplasma septic arthritis),
bowel changes (villous atrophy)
Autoimmune thyroidits, AIHA, AI thrombocytopenia
Treatment: vigilance and treatment of infx
immunoglobulin replacement therapy
Prognosis: pretty good! Surveillance for tumours
(lymphoma and gastric ca)
Ref: Park et al., Lancet 2008; 372: 489-502
24. Common Variable Immune Deficiency
(CVID)
Form of Primary Antibody Deficiency,
heterogeneous group of disorders
Prevalence: variable 1 in 50,000
Age:bimodal: mid childhood
early adulthood
Recurrent sinopulmonary infections, bronchiectasis
Genetics: No clear inheritence, ICOS, CD19, BAFFR and TACI mutations linked to only 10% cases
25. Summary of learning objectives
Understanding of the use and interpretation of
certain tests with reference to relevant clinical
conditions
Immunoglobulins
Complement
Acute antibodies / C-ANCA
Cryoglobulins
Anti-nuclear antibodies