Immunodiagnostics Flashcards
JVIM 2022 Autoantibody review - what diseases have autoantibody detection been studied in
IMHA - DAT, other anti-erythrocyte Ab detection methods were superior to DAT (flow, ELISA); SAT
ITP - flow and ELISA detection of anti-plt AB. Not specific for primary ITP
IMN - small study demonstrated anti-neutrophil cytoplasmic Ab in 5/6 dogs.
HypoTH - antiTg positive in 35-60% of cases; increased false positives in nonthyroidal illness
DM - small studies with various results for different antigens tested.
HypoA - one small study
Rheumatoid factor - one study reported positivity in 70% of RA patients. Also useful in SLE
ANA - various different antigens in this panel, result as titre, high false negative rate in SLE. recommended if >1 other indicator of SLE.
GI - pANCA or ANCA were elevated in dogs with IBD compared to healthy controls and other causes of diarrhoea
Sens 80%; Spec 93-99%. Smaller study also showed utility in early detection of PLE in dogs (prior to low albumin)
Cardiac - small study of ARVC dogs found positive result to anti-cardiomyocyte Ab in affected dogs but not controls.
Neuro - MM and MG serum titres. Also newer anti-ryanodine fusion protein receptor Ab in alternate cause of MG.
MUE - detection of anti-astrocyte or Glial Ab in CSF have shown variable diagnostic use.
JVIM 2022 AutoAb review identified areas of lack of information
- most studies are small
- lack of negative case controls for comparison
- use of different measurement techniques limits comparison b/w studies
- lack of statistical calculations
What are acute phase proteins and how should they be used
Proteins/markers that change by >25% in response to inflammatory stimulus.
Dogs = CRP, SAA, haptoglobin
Cats: SAA, AGP, haptoglobin
Negative markers are albumin and antithrombin
Major = rapid rise early in disease then also decline fairly rapidly with resolution.
Ideally should be assessed as a panel including at least 1 major positive and negative marker as this allows for an assessment of the overall response (such as elevated AGP in cushings but no change in negative proteins).
It is likely that they are most useful as an aid to monitoring inflammatory processes and not as a specific diagnostic test as they can be altered by many different pathological processes. They may be prognostic in some disease cases.
Evidence for CRP use in infectious diseases
Known to increase in bacterial and viral acute infections and some chronic infections
Studies have demonstrated a decline that corresponds with clinical response to treatment (and radiographic resolution of pneumonia symptoms).
Elevations are often more severe in infectious pyometra compared to CEH (though there is overlap)
- in canine parvo the initial magnitudeo f increase was not prognostic but rate of decline over first 24-48h was.
- JSAP 2019 study using CRP as outcome measure found single measurements were not prognostic, but serial changes were correlated with outcome.
- JVIM 2022 study demonstrated serial measurement of SAA and CRP was correlated with disease resolution in septic peritonitis, pyometra and pneumonia
Evidence for CRP use in parasitic disease
Use in monitoring for resolution of Babesia gibsoni infection has been reported, using serial measurements as a surrogate for infection detection
- Also been reported as a surrogate marker for flare up of autoimmune reactive IMPA in patients with chronic rickettisial infections.
reported as sensitive marker of diskospondylitis in a recent study but is not specific (more sensitive than other serological of haematological markers of inflammation).
Elevated in HW disease and possibly in Toxo/Neo.
Evidence for CRP use in surgery
Magnitude of increase is not correlated with the severity of trauma
But increase after initial decline may be useful in detecting post operative complications
Was not predictive of outcome or severity of lesion in patients with IVDD
Evidence for CRP use in autoimmune disease
Not specific for any particular disease but it sensitive with increases reported in IMPA, IMHA, ITP and SRMA.
Increases were not reported in a MUE study - suspected to be because there is no systemic inflammation in these patients and the inflammation is localised/sequestered.
Able to aid in differentiation of IMPA from OA in older dogs - serum elevation in CRP correctly categorised 62/65 dogs in one study
May be useful in monitoring response to treatment and relapse in some diseases but studies on this are mostly lacking for individual disease (some small studies in SRMA have reported correlation with relapse)
Evidence for CRP use in Pancreatitis
2 recent studies reported correlation with disease activity indexes and cPLi.
This in turn is correlated with outcome
Again it is the trend in CRP which seems most important rather than single measurements
Evidence for CRP use in Neoplasia
Increases are seen not because of tumour but becaue of secondary inflammation - so some tumours are more likely to generate an increase than others. Though such studies are lacking and increases have been reported in a wide range of tumour types
In solid tumours increases were seen later in the disease process (ie at metastasis) compared to haematopoietic tumours where increases seem to be highest and may show some evidence of being correlated with relapse when increasing in lymphoma dogs in remission.
Evidence for CRP use in GI upset
One study found no difference in dogs with IBD vs other GI dz
A recent study identified value of CRP as predictive of severity of duodenal lesions
Limitations of ANA titres
While useful in investigation of SLE they are not elevated in all cases and they can be elevated in non-immune disease such as chronic infection and neoplasia.
Also, the technique to measure varies between labs so results are not directly comparable.
SLE positivity has been reported in anywhere from 70-95% of SLE cases.
