Most of the autoantibodies are relatively non-specific. Nevertheless, they are in aid for establishing a diagnosis (Table 13).
Tab. 13 ANA and incidence of diseases
| Antibody |
Disease |
Incidence (%) |
anti-CENP-B |
CREST-syndrome
systemic scleroderma |
80 - 90
10 - 48 |
anti-ds-DNA |
SLE |
50 - 90 |
anti-ss-DNA |
SLE
drug-induced LE
MCTD (sharp syndrome)
polymyositis/dermatomyositis
systemic scleroderma, Sjögren’s syndrome, RA |
70 - 95
- 60
20 - 50
40 - 50
8 - 15 |
anti-fibrillarin |
progressive systemic sclerosis |
5 - 10 |
anti-histone |
drug-induced LE
SLE
RA |
20 - 40
30 - 70
15 - 50 |
anti-Jo-1 |
dermatomyositis
polymositis
polymyositis+interstitial lung disease |
- 5
- 30
- 70 |
anti-Ku |
SLE
polymyositis/dermatomyositis, progressive systemic sclerosis |
- 10
> 50 |
anti-PM-Scl (PM1) |
polymyositis
dermatomyositis
progressive systemic sclerosis |
50 - 70
- 10
5 - 10 |
anti-proliferative cell nuclear antigen |
SLE |
- 50 |
anti-RNA-polymerase 1 |
progressive systemic sclerosis |
- 4 |
anti-Scl-70 |
progressive systemic sclerosis |
40 - 70 |
anti-Sm |
SLE |
25 - 75 |
anti-SS-A/Ro |
Sjögren’s syndrome
SLE
neonatal LE |
40 - 95
20 - 60
- 100 |
anti-SS-B/La |
Sjögren’s syndrome
SLE |
40 - 95
10 - 20 |
anti-U1-snRNP |
MCTD (Sharp Syndrome)
SLE |
95 - 100
30 - 40 |
In contrast to them, a few subtypes have proved to be very specific for some connective tissue diseases (Table 14).
Table 14 Relatively specific autoantibodies
Relatively specifc antibodies for |
Therapy and monitoring |
anti-ds-DNA for SLE |
RF-IgA |
anti-sm for SLE |
RF- IgG |
anti-Histones for drug-induced SLE |
anti-ds-DNA |
anti-U1-snRNP for MCTD |
ANCA |
anti-Ro/SS-A for Sjögren syndrome |
anti-mitochondrial (Type 2) |
anti-La/SS-B for Sjögren syndrome |
|
anti-Centromere for CREST syndrom |
|
anti-Scl-70 for systemic sclerosis |
|
ANCAs for vasculitides |
|
anti-mitochondrial-Type 2 for PBC |
|
Although it has been difficult to link autoantibodies to pathogenesis, they can be used to predict disease progression and outcome. For example, autoantibodies directed against topoisomerase are associated with progression of scleroderma to diffuse skin involvement and severe systemic disease, whereas antibodies to centromere proteins predict a more slowly progressive disease and development of a limited variant of scleroderma. In addition, certain models of autoantibody production hold promise of a clearer understanding of the mechanisms that underlie autoimmunity.
Nowadays there are several relatively specific screening and identification methods for the diagnosis and/or follow-up of autoimmune diseases available. The type of assay used crucially influences diagnostic value of the parameters. In generally, the less time consuming ELISA using well characterized antigens should be preferred in routine laboratories, although they tend to produce more false positive and true weak positive results, which may reduce the positive predictive value.
A diagnostic stepwise scheme is proposed in Table 15.
Thereby, the ”classical” RF should be more and more replaced by the more specific RF-subclasses. In case of ANA the IFA is an effective screening assay in patients with suspect autoimmune diseases. HEP-2 are the most sensitive tool for ANA screening. Positive samples showing a centromere, or nucleolar, speckled, homogenous, peripheral or mitochondrial pattern should be subjected to appropriate and more specific assays for the identification and verification of antibodies against characterized antigens. In case of antiphospholipid antibodies specific ELISA should be preferred instead of the often rather poorly defined anticoagulant tests.
In generally, the measured laboratory results can only properly interpreted when they are seen in the light of the clinical details and when the limitations of the technologies currently have been taken into consideration.
|
(ANCA)
