Uncertainty of measurement:
SSA 16%
Ro52 20%
SSB 20%
Sm/RNP 20%
Sm 20%
Scl-70 30%
Jo-1 30%
Ribo-P 30%
| Age Range | Either Sex |
|---|---|
| All | < 30 |
| Age Range | Either Sex |
|---|---|
| All | >= 41 |
| Age Range | Either Sex |
|---|---|
| All | 31 - 40 |
Performed 2-3 times a week depending on demand.
At LabPLUS, apart from Ro-52 antibodies, all new reactive ENA antibody results by luminex methodology are tested by second-round line immunoassay (LIA) methodology and final reportable results are combinations of this dual methodology testing in addition to ANA testing outcomes.
With respect to U1-RNP the luminex assay has both a duplex and anti-Sm/RNP bead as well as a specific U1-RNP bead. Patient sera demonstrating any reactivity to either bead has second-round LIA testing. The LIA has antigens for anti-Sm, anti-Sm/RNP, U1 NNP specific proteins [A], [C] and [70kD]. The manufacturer's algorithm is followed to determine U1-RNP specificity. Under our testing conditions, review of testing data indicated that the luminx U1-RNP bead, while being very sensitive, lacked diagnostic specificity which is why second-round LIA testing is required for this analyte.
The ENA is used to assist in the diagnosis of connective tissue diseases. They will, in most cases, cause a positive ANA. The diagnosis of a connective tissue disease cannot be made on the basis of antibodies to ENA antigens alone. The results must be interpreted in light of the patient's history and physical findings as well as other tests. The levels of antibody do not necessarily correlate with severity or duration of disease. Some patients with severe clinical disease may have very low / undetectable levels of these antibodies.
Connective tissue diseases are systemic autoimmune disease which is, most often, selectively directed against a specific organ. Their classification is based on clinical and biological data. The detection of autoantibodies often occurs before any definite signs and symptoms.
ENA should generally only be ordered when there are definite clinical features to suggest a connective tissue disease and when ANA is positive (see https://choosingwisely.org.nz/professional-resource/nzra/ )
Methodology
At LabPLUS, apart from Ro-52 antibodies, all new reactive ENA antibody results by luminex methodology are tested by second-round line immunoassay (LIA) methodology and final reportable results are combinations of this dual methodology testing in addition to ANA testing outcomes.
With respect to U1-RNP, the luminex assay has both a duplex anti-Sm/RNP bead as well as a specific U1-RNP bead. Patient sers demonstrating any reactivity to either bead has second-line LIA testing. the LIA has antigens for anti-Sm, anti-Sm/RNP, U1 NNP specific proteins [A], [C], and [70kD]. The manufacturer's algorithm is followed to determine U1-RNP specificity. Under our testing conditions, review of testing data indicated that the luminex U1-RNP bead while being very sensitive lacked diagnostic specificity which is why second-round LIA testing is required with this analyte.
Currently LabPLUS uses luminex and line immunoassay methodology to detect the common ENA specificities. The final report will depend on these results interpreted with the ANA pattern.
What follows is an overview of each of the reportable ENA antibodies at LabPLUS:
Ro 52 antibodies
These antibodies are NOT disease specific . They are found in a number of autoimmune diseases including SLE, primary Sjogren's syndrome and Inflammatory myositis. They may occur in many inflammatory disease states but are generally more significant if associated with other autoantibody specificities (e.g. SSA, Jo-1 and Scl-70)
SSA and SSB antibodies
Antibodies to SSA (previously termed Ro) are directed at the 60 kDa protein subunit and are associated with various autoimmune diseases. They most commonly appear in patients with Sjogren's syndrome (40-95% of cases) but can also be found in SLE (20-60%) and PBC (20%). They can also be occasionally found in cases of both autoimmune and viral hepatitis. At LabPLUS, the ANA cell line hyper-expresses SSA antigen and gives a very specific fluorescent pattern when SSA antibodies are present in patient sera. This feature is used to correlate the luminex specificity for SSA antibodies. In the setting of anti-SSA luminex reactive and ANA negative, second round LIA testing will be used to determine anti-SSA assay specificity.
In virtually 100% of cases, SSA antibodies are found in neonatal lupus syndrome. They are transmitted from mother to the foetus transplacentally where they cause inflammatory reactions as well as a congenital AV heart block.
Antibodies to SSB (previously termed La) are found almost exclusively in females. Highest frequencies of the antibody are seen in Sjogren's syndrome (40-95%), SLE (10-20%) and neonatal LE (75%).
When both SSA and SSB antibodies are present in a clinically compatible setting, their presence is virtually diagnostic of either primary or secondary Sjogren's syndrome.
Please note: Ro-52 antibodies are NOT the same as SSA (Ro) antibodies
Sm antibodies
These antibodies have a very high specificity (99%) but low prevalence (5-10%) for SLE in Caucasian patients. Antibody prevalence is significantly higher in other ethnicities with SLE (i.e. Arabic 20-40%, Chinese 20% and Black Africans 30%)
U1 RNP antibodies
By definition, anti-U1 RNP antibody reactivity is seen in patients with mixed connective tissue disease (MCTD). MCTD combines the clinical characteristics seen in RA, SLE, PSS and polymyositis. U1 RNP antibodies can be present in patients
with SLE, PSS and Poly / Dermatomyositis but in much lower prevalence (range: 10-40%).Scl-70 antibodies
These antibodies are considered a diagnostic marker for systemic sclerosis (PSS). Overall they have an assessed prevalence of 75% in patients with PSS; however the antibodies are seen in significantly higher prevalence (40-80%) in the diffuse cutaneous form versus the limited cutaneous form (5-15%)
When present, these antibodies give a very characteristic staining pattern on the Hep-2000 ANA cell line which assists in establishing the specificity of results generated by both luminex and LIA ENA testing methodologies.
Anti Jo-1 and Ribo-P antibodies
The clinical significance of these antibodies is detailed under the ANA entry in the Test Guide.
References
1. Euroimmun ANA Profile 5 IFU
2. Autoantibodies in Organ Specific Autoimmune Diseases: A Diagnostic Reference; Conrad K, Schobler W, Hiepe F, Fritzler MJ. Pabst Science Publishers 2011.
For further information contact the laboratory, (09) 307 4949 ext 22103 or:
Associate Professor Rohan Ameratunga
, Immunopathologist: Locator
93-5724,