Generality
In laboratory medicine, the abbreviation ANA - an acronym for Anti-nuclear antibody (trad. Anti-nucleus antibodies ) - identifies a vast and heterogeneous population of anomalous antibodies, directed against components of human cells, in particular nuclear (DNA, RNA, ribonucleoproteins, histones, centromere etc.). It is therefore autoantibodies, that is immunoglobulins directed against healthy and normal components of the organism, wrongly interpreted as dangerous (antigens), therefore considered worthy of an immune attack.
For example, practically all patients with systemic lupus erythematosus or mixed connective tissue disease are positive for ANA.
There are different cellular components to which the attack of antinuclear antibodies is recorded.
The term antinucleo is linked to the fact that the first antibodies discovered were directed against nuclear antigens . Today, that of anti-nucleus antibodies is an obsolete terminology, since several target autoantigens, clinically important in some systemic autoimmune diseases, are also located in the cytoplasm (therefore outside the nucleus).
As anticipated, there are different types of anti-nucleus antibodies, classified according to the self-antigens to which they are directed. Each of these antibodies has particular specificity for some autoimmune diseases; this means that the raising of his blood values is a spy that signals the possible presence of a very specific disease.
What's this
Anti-nucleus antibodies (ANA) are a group of antibodies produced by the immune system, which, due to an altered activity, is no longer able to recognize the "self" (parts of the organism to which it belongs) from the "non self ”(Substances foreign to the body). These autoantibodies mistakenly attack the body's healthy cells, causing signs and symptoms such as inflammation of organs and tissues, fatigue and joint and muscle pain. Specifically, the ANAs recognize some substances found in the nucleus of the cell, hence the name "anti-nucleus". This results in damage to organs and tissues.
The presence of ANA can be considered a marker of an autoimmune process and makes it possible to exclude other conditions with similar signs and symptoms. The disease in which they are most frequently found is systemic lupus erythematosus (SLE) .
Why do you measure
The anti-nucleus antibody test (ANA) identifies the presence of these autoantibodies in the blood. This finding may be related to some autoimmune disorders.
In particular, the examination of anti-nucleus antibodies is mainly used as a test to support the diagnosis of systemic Lupus erythematosus (SLE) .
In relation to the signs and symptoms that the patient manifests, and to the suspected pathology, the ANA test can be used together with other investigations, such as:
- ENA panel;
- Anti-ds DNA antibodies (double stranded DNA), anti-centromere (region through which two chromosomes are bound together) and / or anti-histone (proteins that allow the packaging of DNA);
- Evaluation of erythrocyte sedimentation rate (ESR) and / or C-reactive protein (PCR).
Note
The ANA test is not used to follow or monitor the clinical course of the LES, so this examination is not usually required in a serial fashion.
When do you take the exam?
According to the common clinical practice, the detection of antinuclear antibodies is carried out only in front of a clinical suspicion for systemic autoimmune diseases .
In general, ANA research is not recommended as a screening test in subjects with no suggestive symptoms and risk factors.
If the examination is considered necessary, in a first step a dosage of the total titre of antinuclear antibodies in the blood is carried out, without going into the specific immunoglobulin specifics. Only in the presence of positive antibody titers, associated with the clinical suspicion of an autoimmune disease, will the dosage of the single autoantibodies be performed to obtain further diagnostic indications.
Normal values
ANA antibody titres higher than 1:40 (or at concentrations of 5 IU / mL) are considered positive. High titers (> 1: 160 or concentrations of 20 IU / mL) are particularly suggestive of a systemic autoimmune disease.
- Titles less than 1:40 should be considered negative and their patients, if they have no symptoms, are not affected by autoimmune diseases;
- Titles greater than 1:40 and less than 1: 160 should be considered low positive: the patient should not be subjected to in-depth diagnosis, but only to monitoring over time;
- Titles equal to or greater than 1: 160 are to be considered positive and patients should undergo in-depth diagnosis, since it is likely that they will be affected by an autoimmune disease.
PLEASE NOTE:
- about 31% of normal subjects have an ANA titer of 1:40;
- about 5% of normal subjects have an ANA titer of 1: 160.
Anti-High Core Antibodies - Causes
The dosage of anti-nucleus antibodies is particularly sensitive, but poorly specific. This is because, as we have seen, ANA antibody titers tend to be higher than normal under different conditions, including:
- Normal subjects: especially if of advanced age and female gender;
- Burn patients;
- Subjects being treated with special drugs: procainamide, hydralazine, isionazide, minocycline, penicillamine, anticonvulsants, diltiazem, chlorpromazine, methyldopa;
- Patients with particular infectious diseases: Epstein-Barr virus, tuberculosis, subacute bacterial endocarditis, malaria, hepatitis C;
- Patients with systemic autoimmune diseases: SLE, scleroderma, mixed connective tissue, dermatomyositis, Sjögren's syndrome, rheumatoid arthritis, juvenile idiopathic arthritis, polymyositis;
- Patients with specific organ autoimmune diseases: autoimmune hepatitis, autoimmune primary cholangitis, autoimmune thyroiditis.
Associated symptoms
Autoimmune diseases can involve various manifestations, vague and non-specific. Often, these disorders change over time, becoming progressively more severe, or alternating periods of remission with periods in which the symptoms become acute.
The alarm bells associated with systemic autoimmune disorders include:
- grade fever;
- Persistent fatigue and weakness;
- Red skin rash (in the LES, a butterfly-like stain between the nose and cheeks is typical);
- Skin photosensitivity;
- Hair loss;
- Joint and / or muscle pains;
- Numbness or tingling in the hands and feet;
- Inflammation and injury to various organs and tissues, including kidneys, lungs, heart, lining membranes of the heart, central nervous system and blood vessels.
ANA Bass - Causes
A negative ANA test suggests that an autoimmune disorder is unlikely. If symptoms recur, however, it may be useful to repeat the exam.
In the case of low anti-nucleus antibodies (not present), the doctor will establish the diagnosis once all the data needed are collected.
How to measure it
For the analysis of Anti-Nucleus Antibodies, the patient must have a blood sample taken from a vein in his arm.
To determine and measure ANA, it is possible to use two different types of tests:
- IFA method (indirect immunofluorescence assay): it is considered the "gold standard" (reference) method to establish a diagnosis. The patient's blood sample is mixed with the cells that are attached to the slide. Autoantibodies that may be present in the blood react with cells. The slide is treated with a reagent containing fluorescent antibodies and examined under a microscope. What is observed is the presence (or absence) of fluorescence. In the report, the result is reported as a title, in turn expressed as a report.
- Immunometric test (enzyme linked immunosorbent assay-ELISA or immunoenzymatic test-EIA): it is performed with automated instruments, but is less sensitive than the indirect immunofluorescence assay in the determination of ANA. Therefore, this method can be used for ANA screening; a positive or equivocal result is then submitted to the IFA. The result is usually reported as a number followed by a unit of measurement.
Preparation
Before undergoing the examination, the patient must observe a fast of at least 8-10 hours, during which a small quantity of water is allowed. Furthermore, it must be in an upright position for at least 30 minutes.
Interpretation of Results
The pathologies associated with a positive ANA test are different, but the most common finding is associated with the LES.
Other disorders in which anti-nucleus antibodies are elevated may include:
- Drug-induced lupus;
- Sjögren syndrome;
- Scleroderma (systemic sclerosis);
Less commonly, ANAs may be present in people with:
- Raynaud's syndrome;
- Arthritis;
- Dermatomyositis or polymyositis;
- Mixed connective tissue disorders;
- Other autoimmune diseases.
A positive ANA test result may also depend on:
- Use of certain drugs;
- Some infections;
- hepatitis;
- Primary biliary cirrhosis.
To establish a diagnosis, the doctor must rely on the result of the ANA test and other in-depth investigations, on the patient's symptoms and clinical history.
Types of antinuclear antibodies
Although overall high ANA antibody titers demonstrate a high correlation with several autoimmune diseases:
| Autoimmune hepatitis | They represent one of the diagnostic criteria |
Systemic lupus erythematosus | They represent one of the diagnostic criteria. They are not as useful for prognostic or disease monitoring purposes. |
Drug-induced lupus | They are present in 95% of patients |
Mixed connectivity | They are present in 100% of patients |
Sjogren's syndrome | They are present in 80-90% of patients |
Systemic scleroderma | They are present in 70-80% of patients |
Dermatomyositis | They are present in 10-50% of patients |
Juvenile idiopathic arthritis | They are present in 80-90% of patients with mono-pauciarticular form |
Some of these antibodies seem to assume a very specific diagnostic and / or prognostic significance in some diseases. In this regard we report the data extrapolated from some of the sources consulted in the drafting of the article (click on the images to enlarge).
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