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Immunology test A-C

Available tests
Assay Sample Type (Bottle) Reference range Clinical indications Limitations/interferences Technical
information
Clinical
sensitivity & specificity and/or Interpretation
Assay Acetylcholine
receptor antibodies
Sample Type (Bottle) Serum. Reference range 0.2-0.5 nmol/L Clinical indications Results are
positive in as many as 90% of patients who have generalized Myasthenia Gravis
(MG) but in only 50-70% of those who have only ocular MG; thus false
negatives are common in cases of purely ocular MGs.  These antibodies have high specificity
(>95%) for the diagnosis of MG. Level of antibodies do not correlate with
disease activity, so repeated testing is not indicated.  In patients with suspected MG who are
negative for ACRA, anto-MuSK (muscle-specific receptor tyrosine kinase)
antibodies may be indicated.
Limitations/interferences Occasional false
positives can be seen in patients with low titre antibodies and/or positive
rheumatoid factor.
Technical
information
Turnaround time:
14 days Type of investigations: ELISA
Clinical
sensitivity & specificity and/or Interpretation
Sensitivity = 80%
Specificity > 95%  Weak Positive =
0.2 - 0.5 nmol/L Positive = 0.5 - 5.0 nmol/L 
 Strong Positive = > 5.0
nmol/L
Assay Adrenal
cortical antibodies
Sample Type (Bottle) Serum. Reference range Negative or
Positive
Clinical indications Antibodies are
directed to 21-hydroxylase in patients with idiopathic hypoadrenalism
(Addison’s disease) and 17-αhydroxylase enzyme in patients with autoimmune
polyendocrinopathy-candidiasis-ectodermal dystrophy (also known as Autoimmune
polyendocrine syndrome 1).
Limitations/interferences Antibodies cause
gradual steroid cell destruction leading to adrenocortical insufficiency
therefore repeated testing is not indicated.
Technical
information
Turnaround time:
10 days    Type of investigations: IIF
Clinical
sensitivity & specificity and/or Interpretation
99% specific 90%
sensitive for APECED,  60% for
Addison’s Disease
Assay Alpha-1
anti-trypsin concentration (Assay performed in Biochemistry
Laboratory)
Sample Type (Bottle) Serum. Reference range 0.78- 2.0
g/l
Clinical indications Measurement of
AAT is indicated in the investigation of chronic obstructive airway disease,
emphysema and in neonatal and adult liver disease where low concentrations
have diagnostic importance. AAT deficiency has autosomal dominant inheritance
occurring in 1/2000 -   5000.  If deficiency is found phenotyping of the
alleles will be performed (see AAT-PI)
Limitations/interferences Grossly lipaemic,
icteric or haemolysed samples
Technical
information
Turnaround time:  1 days 
  Type of investigations:
turbidimetric
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Alpha-1
anti-trypsin phenotyping
Sample Type (Bottle) Serum. Reference range N/A Clinical indications Any alpha-1
anti-trypsin concentration ≤1.2 g/l is referred for phenotyping.  A1AT is known to have over 75 phenotypes.
Most are clinically insignificant but some are associated with complete or
partial deficiency of the protein in serum which includes alleles which are
homozygous or heterozygous for S or Z. When phenotyping is not conclusive
A1AT genotyping can be performed after discussion with Duty Doctor.
Limitations/interferences Grossly lipaemic,
icteric or haemolysed samples
Technical
information
Turnaround time: 15 days    Type
of investigations: Isoelectric focusing
Clinical
sensitivity & specificity and/or Interpretation
A ZZ homozygous
individual is predisposed to lung  and
liver disease. A heterozygous (MZ) individual  is at a small risk of developing liver
disease but has  little increased risk
of developing lung disease.   The  SZ variant results in significantly reduced
serum concentrations of alpha-1-antitrypsin and a predisposition to lung
disease, especially in smokers, and liver disease.
Assay Alkaline
phosphatase isoemzymes
Sample Type (Bottle) Serum. Reference range Liver, Bone,
Intestinal, Placental, or any combination
Clinical indications Causes of a
raised ALP can be physiological (e.g. growth/development, pregnancy, gender,
transient hyperphosphatasaemia of infancy, macro-ALP complexes) or
pathological (e.g. Paget's disease, extra-hepatic biliary tree obstruction, malignancy).
Isoenzyme studies are performed to determine which of the predominant
isoenzyme, either bone, liver, intestine or if pregnant, the placenta, is
causing the total increase.
Limitations/interferences Grossly lipaemic,
icteric or haemolysed samples
Technical
information
Turnaround time:
21 days    Type of investigations:  Gel electrophoresis
Clinical
sensitivity & specificity and/or Interpretation
Interpretative
comments used depending on result.
Assay ALPS
immuno-phenotyping
Sample Type (Bottle) EDTA Reference range 0-2.5% TCRαβ
double negative CD3+ T cells
Clinical indications One of the
criteria for diagnosing Autoimmune lymphoproliferative Syndrome (ALPS) is
elevated TCRαβ double negative CD3+ T cells (>1.5% of total lymphocytes
for >2.5% CD3+ lymphocytes) in the setting of normal or elevated
lymphocyte count.  The main clinical
presentation for this condition is lymphadenopathy in children for which no
infectious or malignant cause was found. These patients also can develop
autoimmune disease eg. Autoimmune Thrombocytopenia or autoimmune haemolytic
anaemia. If you suspect this condition please speak to Clinical Immunologist.
Limitations/interferences Refrigerated
specimen Clotted Grossly hemolysed
Technical
information
Turnaround time:  5 days 
  Type of investigations:  Flow cytometry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Anti-Nuclear
Antibodies (ANA)
Sample Type (Bottle) Serum. Reference range 0-0.9 units Clinical indications Our routine assay
is a florescent immunoassay which detects antibodies to:  U1RNP/RNP70/Sm/Ro/La/Scl-70/Jo-1,
centromere, dsDNA, fibrillarin, Pm-Scl, RNA Polymerase III, Mi-2, Ribosomal
P, and PCNA(Proliferating Nuclear Antigen). 
Positive ANA will automatically be followed up by dsDNA testing and
specific ENA characterisation.  In
cases of high ANA ELISA results with negative dsDNA and ENA characterisation
confirmation by HEp2 cell IIF will automatically be performed with further
cascade testing occurring as required. Also see Myositis/Scleroderma Line
Blot.
Limitations/interferences Assay only
detects antibodies to the most clinically significant connective tissue
disease antigens.  A negative result
does not preclude the presence of other ANA disease associated antibodies. If
there is a high clinical suspicion of connective tissue disease, then HEp2
cell IIF should be performed in addition. Occasional false positive results
caused by antibodies to carrier proteins have been seen, but will be
identified by follow-up investigations.
Technical
information
Turnaround time:  3 days 
  Type of investigations:  FEIA
Clinical
sensitivity & specificity and/or Interpretation
Sensitivity:    U1RNP
– 30-70% SLE 100% MCTD;      Sm - 10-30% SLE;    Ssa/Ro
- 25 - 50 %  SLE; 60 - 90 % SS Neonatal
Lupus > 95 %; ;  SSb/La - SLE 5 - 15
%  40 - 95 % SS  Scl-70 - 
20 - 70 % Scleroderma    Centromere: 
40-90% limited cutaneous scleroderma                     Jo-1: 60-80% anti-synthetase syndrome
(Myositis)
Assay Anti-neutrophil
cytoplasmic antibodies (ANCA) (IIF screen)
Sample Type (Bottle) Serum. Reference range Negative Clinical indications There are two
major subclasses of ANCA, characterised by staining patterns found when using
fixed human neutrophils as substrate under Indirect Immunofluorescence (IIF):  1. C-ANCA (Cytoplasmic or Classical
Staining ANCA), denotes a granular cytoplasmic staining pattern on ethanol
fixed neutrophils, with some interlobular accentuation. C-ANCA are
principally directed against a proteinase 3 (PR3) present in the azurophil
granules in the cytoplasm of human neutrophils.  Positive C-ANCA is suggestive but not diagnostic
of Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA)
(and its renal limited variant) and Churg-Strauss. C-ANCA positive results
must be followed up by ELISA tests for anti-MPO and anti-PR3.  2. P-ANCA (Perinuclear Staining ANCA);
denotes a staining pattern present in the perinuclear space of the cytoplasm
of ethanol fixed neutrophils. P-ANCA antibodies are principally directed
against myeloperoxidase (MPO), which is also found in azurophil granules in
the cytoplasm of human neutrophils.  ANCA
measurements are not closely associated with disease activity and should
therefore not determine treatment increases or decreases. However treatment
withdrawal in patients with a persistently positive ANCA is associated with
relapse.  Other P-ANCA antigen
specificities are for elastase and lactoferrin. P-ANCA is associated in MPA
and in some cases of GPA and Churg-Strauss syndrome although can also be seen
in inflammatory bowel disease and other autoimmune diseases. P -ANCA positive
results must be followed up by ELISA tests for anti-MPO and anti-PR3.
Limitations/interferences Technical
information
Turnaround time:  3 working days    Type
of investigations:   IIF
Clinical
sensitivity & specificity and/or Interpretation
Results are
reported as WEAK POSITIVE, POSITIVE, ATYPICAL or NEGATIVE. POSITIVE samples
are assayed by ELiA immunoassay method for PR3 and MPO reactivity.  Atypical P-ANCA patterns are reported as
ATYPICAL PATTERN and these may be seen in primary sclerosing cholangitis and
Crohn's disease.  Samples which may
have an ANA present will have MPO and PR3 analysed have a comment stating
that ANA is present on the report. 
This test should only be requested if there is a high suspicion of
vasculitis due to the poor negative predictive value and potential for false
positives.
Assay β2
Microglobulin (performed
in biochemistry)
Sample Type (Bottle) Serum. Reference range 1.00 - 2.40 mg/l Clinical indications In Multiple
Myeloma B2M is found to be the single most effective prognostic marker. Repeat
testing is not indicated.
Limitations/interferences High
concentrations can also be found in patients with renal dysfunction and other
connective tissue diseases where this test is rarely of clinical utility.
Technical
information
Turnaround time:  1 day 
  Type of investigations:
Turbidimetry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Beta Trace Sample Type (Bottle) Nasal or Ear
fluid.
Reference range >2.0mg/L
suggests presence of csf >6.0mg/l strongly suggests CSF presence.
Clinical indications Beta trace (also
known as prostaglandin D synthetase) is a protein found at high concentration
in csf (20mg/L) and low concentration in normal serum (0.5 mg/L). Its
measurement is useful in patients with otorrhoea or rhinorrhoea to identify
the presence of CSF.
Limitations/interferences Technical
information
Turnaround time:  3 days 
  Type of investigations:
Nephelometry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Caeruloplasmin Sample Type (Bottle) Serum. Reference range 0.2 - 0.5
g/L(adults) ranges for other ages quoted on report
Clinical indications Low serum concentrations
are seen in the majority of patients with Wilson's disease, an inherited
defect of copper metabolism
Limitations/interferences Concentrations
are increased by oestrogens and may be decreased in severe liver disease
Technical
information
Turnaround time:  5 days 
  Type of investigations:
Nephelometry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Cardiac muscle
antibodies
Sample Type (Bottle) Serum. Reference range Negative Clinical indications Cardiac  muscle 
antibodies  (ACMA)  are 
positive  in  a 
proportion  of  patients 
with  Dressler’s  Syndrome  following myocardial infarction, after
cardiac surgery, acute rheumatic fever and in some cardiomyopathies.  However diagnostic value is low.
Limitations/interferences Technical
information
Turnaround time:
10 days    Type of investigations: IIF
Clinical
sensitivity & specificity and/or Interpretation
Assay referred to
Sheffield Immunology  ACMA have a
sensitivity of 90 % and a specificity of 80 % for idiopathic dilated
cardiomyopathy  (IDCM).  There is a 95 % negative predictive value
in the distinction between IDCM and coronary disease but ACMA are not usually
required to make diagnosis.
Assay Cyclic
Citrullinated Peptide(CCP) antibodies
Sample Type (Bottle) Serum. Reference range 0-7 iu/ml Clinical indications Anti-CCP has a
similar sensitivity for Rheumatoid arthritis as Rheumatoid factor but has
higher specificity. Presence of these antibodies has been found prior to
disease onset and has been associated with erosive disease. These antibodies
indicate diagnosis of RA when seen in early arthritis. However it is not
indicated as a screening test (as per NICE guidance) but should be used in
cases of negative Rf where clinical suspicion is high and to help decision
making on whom to treat with DMARDS.
Limitations/interferences Technical
information
Turnaround time:  3 days 
  Type of investigations:  FEIA
Clinical
sensitivity & specificity and/or Interpretation
Sensitivity =
89%   Specificity = 98%
Assay Centromere
antibodies
Sample Type (Bottle) Serum. Reference range 0- 7u/ml Clinical indications Centromere
antibodies are associated with limited cutaneous systemic sclerosis (CREST
syndrome: Calcinosis, Raynaud’s phenomenon, Oesphageal immobility,
Sclerodactyly and Telangectasia).  They
can also be found in ~10% of patients with Primary Biliary Cirrhosis who may
or may not have features of scleroderma, and in patients with Primary
Raynaud’s.
Limitations/interferences Technical
information
Turnaround time:  3 days 
Type of investigations:  FEIA
Clinical
sensitivity & specificity and/or Interpretation
Sensitivity =
70%
Assay Complement C3
C4
Sample Type (Bottle) Serum. Reference range C3  0.75 – 1.65 g/l         C4 
0.14 - 0.54g/l
Clinical indications Measurement of
serum complement components C3 and C4 is useful in the diagnosis and
monitoring of immune complex disease e.g. SLE and some forms of vasculitis;
angioedema, cryoglobulinaemia, some infections and inherited or acquired
deficiency of complement components. Complement concentrations are acute
phase proteins and may be normal, despite complement consumption, in some
inflammatory and infective disorders. Low levels of C3 and/or C4 can indicate
that there is an increase in consumption or decrease in synthesis. C3 alone
is often decreased in infectious disease (Post- Streptococcal glomerulonephritis,
gram - negative sepsis, endocarditis), patients with C3 nephritic factor, and
inherited or acquired deficiency of C3 and components of alternative
complement pathway (very rare). C3 and C4 are often both decreased in immune
complex disease. C4 alone is characteristically decreased in hereditary or
acquired angioedema (check C1 inhibitor quantitation and function), immune
complex diseases particularly SLE and in cryoglobulinaemia.   Complete C4 deficiencies are very rare;  partial C4 deficiencies are more common and
may be associated with SLE or asymptomatic.
Limitations/interferences Technical
information
Turnaround time:  4 days 
  Type of investigations:
Nephelometry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay C1 esterase
inhibitor (antigenic)
Sample Type (Bottle) Serum. Reference range 0.19-0.39g/l Clinical indications Low levels are
found in 85% of cases of Hereditary Angioedema Hereditary (Type I HAE), the
remaining 15% (Type II) of cases are associated with a non-functioning
protein which gives normal results in immunochemical assays and for which a
functional assay is available. Most commonly associated with decreased levels
of C4.  As HAE is an autosomal dominant
condition family history should be sought. Low levels also seen in acquired
C1 inhibitor deficiency. C1 inhibitor deficiency causes angioedema affecting
peripheries and/or head and neck, or severe abdominal pain due to intestinal
oedema, both lasting more than 24 hours.
Limitations/interferences Technical
information
Turnaround time:  5 days 
  Type of investigations:
Nephelometry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay C1 esterase
inhibitor (Functional)
Sample Type (Bottle) Serum. Reference range 46-130 % Clinical indications Used for the
confirmation of the diagnosis of C1 inhibitor deficiency in patients with
angioedema (especially where the C4 level is reduced and the immunochemical
levels of C1esterase inhibitor are equivocal.) This test should always be
performed once in all new patients with C1 inhibitor deficiency.                                                                       
Where acquired C1 inhibitor deficiency is suspected request paraprotein
studies and C1q level as well. These patients also need screening for
Lymphoma.
Limitations/interferences Sample MUST be
separated and frozen within 60 mins to prevent falsely low function results
Technical
information
Turnaround time:
21 days    Type of investigations: ELISA
Clinical
sensitivity & specificity and/or Interpretation
Clinical
sensitivity = 99%    Clinical specificity = 91%
Assay CD62L shedding Sample Type (Bottle) EDTA. Reference range N/A Clinical indications This test is used to diagnose innate immune defects increasing
susceptibility to pyogenic infection caused by S.pneumoniae, S.aureus or gram
negative bacteria. (IRAK4 or MyD88 deficiency.)
Limitations/interferences These tests can
only be performed after prior discussion with the Consultant Immunologist
Immunology Clinical Scientist.
Technical
information
Turnaround time:
14 days   Type of investigations:  Flow cytometry
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Component
Resolved Allergy testing
Sample Type (Bottle) Serum. Reference range <0.35
kUA/l
Clinical indications Component-resolved
diagnostics (CRD) utilize purified native or recombinant allergens to detect
IgE sensitivity to individual allergen molecules.  These can be helpful in identifying atopic
patients with high likelihood of severe/anaphylactic reactions (such cases
include peanut and venom allergy) CRD can help to confirm patients who have
cross reactive sensitisation that may not lead to severe clinical allergy
(e.g. to betv1 homologues reactions in oral allergy syndrome).  The use of specific CRD must be discussed
with the laboratory prior to testing as a limited number of components are
currently available.  See associated
Table..
Limitations/interferences Results must be
interpreted alongside the clinical context. 
Correlation with history, SIGE testing and SPT is required
Technical
information
Turnaround time:  3 days 
  Type of investigations:  FEIA
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Complement
assays (Functional)
Sample Type (Bottle) Fresh Serum. Reference range New ELISA assay  Classical Pathway Functional ELISA
(LAB8884)  Alternative Pathway
Functional ELISA (LAB8883)   Classical
Pathway: 69 - 129%  Alternative
Pathway: 30 - 113%
Clinical indications Two tests are
performed in conjunction to assess the function of both the classical and
alternate complement pathways (CH100 and AP100).  Indicated for investigation of Complement
deficiency in the setting recurrent infections (Neisseria or encapsulated
bacterial infections), some forms of renal diseases and as a part of follow
up of patients on Eculizumab .
Limitations/interferences Serum sample
transported at room temperature to arrive in the laboratory within 2h of
venepuncture for freezing. It is recommended that all abnormal results be
confirmed by repeat testing to exclude pre-analytical causes of falsely low
functional complement activity.  Please
be aware that due to the change of technology, numerical results will not be
directly comparable between methods. The name, units and reference interval
will change as listed in the reference range section.   EDTA plasma samples should NOT be used as
the chelation of calcium ions renders some of the Complement  components to be inactive.  The Classical functional complement assay
is not suitable for the routine monitoring of patients with SLE
Technical
information
Turnaround time:
6 weeks    Type of investigations: ELISA
Clinical
sensitivity & specificity and/or Interpretation
All abnormal
results are reviewed by a Consultant in the context of the clinical picture.  Low results should be confirmed on repeat
to exclude falsely low results which can occur due to in-vitro degradation of
complement proteins.
Assay Cryoglobulins Sample Type (Bottle) Serum. Reference range Negative Clinical indications Cryoproteins are
serum proteins which reversibly precipitate at temperatures below 37°C.  There are two types of cryoproteins;
cryoglobulins and cryofibrinogens. Cryoglobulins are immunoglobulins which
precipitate in both serum and plasma whereas cryofibrinogens, which contain
fibrinogen-fibrin complexes, only precipitate in plasma. Cryoglobulins can be
further subclassified, according to their immunochemical composition, as Type
I, Type II and Type III. Cryoglobulins are found in a wide spectrum of disorders
but are often transient during viral or bacterial infection. Type I
monoclonal cryoglobulins are invariably associated with haematological
disorders such as multiple myeloma or Waldenstrom’s macroglobulinaemia. Mixed
cryoglobulins, either with (Type II) or without (Type III) a monoclonal
component, are associated infections, autoimmune diseases, immune-complex
vasculitis and liver disease. There is a strong association between hepatitis
C virus infection and mixed cryoglobulinaemia
Limitations/interferences Sample MUST be collected
at 370C. Correct sample handling is imperative for accurate result
generation. Samples must be delivered directly to the
Immunology laboratory by 16:00 Monday to Saturday Not available outside CUH
Technical
information
Turnaround time:  7 days 
  Type of investigations:
Precipitation
Clinical
sensitivity & specificity and/or Interpretation
Reported as
negative or Positive (% of cryocrit - percentage of packed cryoglobulins
referred to total serum after centrifugation at 4°C). If the Type of
cryoglobulin is required please discuss with Clinical Immunologist.
Assay CSF oligoclonal
bands
Sample Type (Bottle) Serum and CSF. Reference range Negative Clinical indications The detection of
IgG oligoclonal bands (OCB) in the CSF is a valuable aid in the diagnosis of
demyelinating disease. OCB can be found in over 90% of patients with
clinically defined MS. NICE guidelines suggest that CSF analysis for the
diagnosis of MS should be made when the diagnosis is clinically uncertain.
They recommend that clinical presentation, exclusion of other causes and
magnetic resonance imaging should be the initial diagnostic tests performed.
Limitations/interferences Both serum and
CSF samples are required for analysis
Technical
information
Turnaround time:
15 days    Type of investigations: Isoelectric
focusing
Clinical
sensitivity & specificity and/or Interpretation
Interpret in
overall clinical context.  Pattern 1:
No oligoclonal bands seen.  Pattern 2:
Oligoclonal bands in CSF only.  Pattern
3: More oligoclonal bands in CSF than in serum. Pattern 4: Same oligoclonal
pattern in CSF and serum. Pattern 5: Monoclonal gammopathy pattern.    Patterns
2 & 3 would signify intrathecal synthesis of Immunoglobulin.
Assay Cytokines Sample Type (Bottle) Li-heparin blood. Reference range N/A Clinical indications TH1 assays > Cytokine induction algorithm to
investigate IFNg and IL12  pathway defects (e.g. patients with primary
or secondary defects predisposing to mycobacterial , salmonella infections
and other relevant pathogens)
T Cell-assays > Cytokine production after various polyclonal T-cell
stimulation (e.g. anti CD3, PHA, PMA/Ionomycine)
Innate assays > Cytokine induction algorithms to investigate
potential innate defects such as Tlr pathway,  IRAK4, NEMO and others
Fungal assays > Cytokine induction assays looking at Th1 but also
Th17 immunity and including response to fungal components in patients with
primary or secondary recurrent/persistent fungal infections, including
suspected lectin pathway defects
Inflammation > Investigation of patients with suspected auto-inflammatory
conditions and related syndromes (e.g. IRIS, or post Transplantation)
including suspected IL10 pathway defects such as IBD.
Limitations/interferences Please send from
Patient and from a healthy control:
 
5-10 ml
Li-heparin blood (3 ml from very small children)
2.7 ml Edta-blood

1-2 ml
Serum/clotted (not for very small children ) Samples must be sent by courier
at ambient  temperature (please do not
cool and avoid overheating) for same or next day delivery to arrive
ideally not later than on a Thursday (exceptions after discussion possible)
Technical
information
Turnaround time:
28-35 days    Type of investigations: Cell culture,
Luminex
Clinical
sensitivity & specificity and/or Interpretation
N/A
Assay Cytokine
antibodies
Sample Type (Bottle) Serum. Reference range Negative Clinical indications Anti-cytokine serology panel > in patients with suspected secondary
immunodeficiency due to anti-cytokine antibodies (e.g. anti IFN gamma, anti
IL6) or conditions known to be associated/aggravated with/by anti-cytokine
auto-antibodies such as Polyglandular syndrome (APS1, APECED), Thymoma,
Pulmonar alveolar Proteinosis (anti GM-CSF) and others.
Limitations/interferences Technical
information
Turnaround time:
28 days    Type of investigations: Luminex
Clinical
sensitivity & specificity and/or Interpretation
N/A