From the Guidelines
The causes of Antinuclear Antibody (ANA) 4+ are multifactorial and can be associated with various systemic rheumatologic disorders, as well as being relatively frequent in healthy individuals, with a specificity of 74.7% for Systemic Lupus Erythematosus (SLE) when using a cut-off point of 1:80 1. When considering the causes of ANA 4+, it is essential to understand that ANA positivity is not exclusive to SLE and can be found in other autoimmune diseases, such as Sjogren’s syndrome, and in healthy individuals.
- The ANA test is sensitive but not specific, and its results should be interpreted in the context of clinical manifestations and other diagnostic criteria.
- A positive ANA result at a titer of 1:80 or higher is considered positive, but this does not necessarily confirm a diagnosis of SLE or any other autoimmune disease.
- The use of ANA detection as an entry criterion in the SLE classification can be considered strategic, but it is necessary to exercise caution when interpreting the results, especially in populations with low SLE prevalence 1.
- To increase the positive predictive value of ANA detection, patients should be preselected using clinical and analytical criteria, and the laboratory report should detail the method used and the results obtained 1.
- The EULAR/ACR 2019 classification recommends ANA detection using the indirect immunofluorescence test (IFI) or a solid-phase ANA screening immunoassay (SPA) with at least equivalent performance, but the lack of precision in the concept of "equivalent performance" can lead to the use of SPAs with insufficient specificity in SLE screening 1.
- The determination of ANA may enable the prediction, diagnosis, and activity determination of certain autoimmune diseases, but it is essential to consider the limitations of the IIFA technique, including its lack of specificity and the potential for false-positive results in healthy individuals 1.
From the Research
Causes of Antinuclear Antibody (ANA) 4+
The causes of Antinuclear Antibody (ANA) 4+ can be attributed to various factors, including:
- Autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease 2, 3, 4
- Certain types of cancers, as ANAs have been found in the serum of patients with different types of cancers, suggesting a potential role in the pathogenesis of cancer 2
- Non-rheumatic diseases, including autoimmune disorders, infectious conditions, and non-autoimmune and non-infectious diseases 5, 6
- Use of specific medications, such as procainamide, hydralazine, and minocycline, which can lead to drug-induced ANA elevation 6
- Presence of certain antibodies, such as antibody to Sm antigen, antibody to native DNA, and antibody to nuclear ribonucleoprotein, which can be associated with specific diseases or conditions 4
Associated Conditions
ANA 4+ has been associated with various conditions, including: