Systemic sclerosis is a systemic autoimmune rheumatic disease characterized by immune abnormalities, leading to vasculopathy and fibrosis. Autoantibody testing has become an increasingly important part of diagnosis and prognostication. Clinicians have been limited to antinuclear antibody (ANA), antitopoisomerase I (also known as anti-Scl-70) antibody, and anticentromere antibody testing. ANA are common in the general population, occurring in up to 20% of women. The presence of an ANA is not necessarily suggestive of a pathologic process, particularly at low titers.
1. Antinuclear Antibodies (ANA)
ANA are common in the general population, occurring in up to 20% of women. The presence of an ANA is not necessarily suggestive of a pathologic process, particularly at low titers
[1]. Rather, low-titer ANA are thought to reflect a state of benign autoimmunity. However, a subset (5–8%) of these individuals will progress to develop a systemic autoimmune rheumatic disease (SARD), such as systemic sclerosis (SSc), Sjogren’s syndrome, or systemic lupus erythematosus
[1]. ANA-positive individuals that subsequently develop a SARD have significantly increased T and B cell activation and increased LAG3
+ T regulatory cells and TGF-ß1
[2][3][4][5]. Immunoregulation usually prevents development of rheumatic disease in ANA-positive individuals. In contrast, immunoregulation becomes impaired in individuals who progress to develop a SARD, resulting in an imbalance favoring inflammation and fibrosis.
Since the 1960s, it has been recognized that ANA are common in individuals with SSc
[6][7]. ANA have been reported to occur in 75–95% of patients with SSc, with a sensitivity of 85% and specificity of 54% on immunofluorescence
[8]. The antigen substrate that is utilized for the assay affects the specificity and sensitivity of ANA differently. An indirect immunofluorescence assay using HEp-2 cells (HEp-2 IFA) is the gold standard technique. The presence of ANA as a result of HEp-2 IFA is reported as a titer and a pattern. A clinically relevant ANA titer is 1:80 or more
[9].
The staining pattern reported with ANA testing by HEp-2 IFA can also be informative. The presence of anti-Scl-70 and anti-U1-RNP antibodies in the sera creates a speckled pattern, while anti-Th/To, anti-fibrillarin (anti-U3RNP) and anti-PM/Scl antibodies create a nucleolar staining pattern. Anti-RNAP I antibodies result in nucleolar staining, while antibodies against RNAP II and III give a speckled appearance or no fluorescence
[8]. With the identification of over 30 staining patterns that span many diseases, an international consensus on antinuclear antibody patterns (ICAP) has proposed a classification system to standardize the interpretation and reporting of staining patterns
[10]. While the presence of ANA and staining patterns is helpful, their absence should be interpreted with caution. For example, the anti-RNAP antibodies demonstrate nucleolar staining only 30–44% of the time
[11][12]. Thus, ANA staining patterns should not be used as the sole screening test for SSc-specific antibodies. ANA-negative SSc patients exist and may reflect a subset of SSc who have delayed progression of nailfold microangiopathy, defined by an early nailfold capillary NVC pattern
[13].
This entry is adapted from the peer-reviewed paper 10.3390/diagnostics13050851