ANAs are found in many disorders, as well as some healthy individuals. These disorders include:
systemic lupus erythematosus (SLE),
rheumatoid arthritis,
Sjögren syndrome,
scleroderma,
polymyositis,
dermatomyositis,
primary biliary cirrhosis,
drug induced lupus,
autoimmune hepatitis,
multiple sclerosis,
discoid lupus,
thyroid disease,
antiphospholipid syndrome,
juvenile idiopathic arthritis,
psoriatic arthritis,
juvenile dermatomyositis,
idiopathic thrombocytopaenic purpura,
infection and
cancer. These antibodies can be subdivided according to their specificity, and each subset has different propensities for specific disorders.
Extractable nuclear antigens Extractable nuclear antigens (ENA) are a group of
autoantigens that were originally identified as antibody targets in people with autoimmune disorders. They are termed ENA because they can be extracted from the cell nucleus with saline. The ENAs consist of
ribonucleoproteins and non-
histone proteins, named by either the name of the donor who provided the prototype serum (Sm, Ro, La, Jo), or the name of the disease setting in which the antibodies were found (SS-A, SS-B, Scl-70).
Anti-Ro/SS-A and anti-La/SS-B staining pattern of anti-nuclear antibodies on HEp-20-10 cells. This staining pattern is seen with anti-Ro and anti-La antibodies.
Anti-Ro and
anti-La antibodies, also known as SS-A and SS-B, respectively, are commonly found in primary
Sjögren's syndrome, an
autoimmune disorder that affects the
exocrine glands. The presence of both antibodies is found in 30–60% of Sjögren's syndrome, anti-Ro antibodies alone are found in 50–70% of Sjögren's syndrome and 30% of SLE with cutaneous involvement, and anti-La antibodies are rarely found in isolation. Anti-La antibodies are also found in SLE; however, Sjögren's syndrome is normally also present. Anti-Ro antibodies are also found less frequently in other disorders including autoimmune liver diseases,
coeliac disease, autoimmune rheumatic diseases, cardiac neonatal
lupus erythematosus and
polymyositis. During pregnancy, anti-Ro antibodies can cross the
placenta and cause
heart block and neonatal lupus in babies. In Sjögren's syndrome, anti-Ro and anti-La antibodies correlate with early onset, increased disease duration,
parotid gland enlargement, disease outside the glands and infiltration of glands by lymphocytes. The mechanism of antibody production in Sjögren's syndrome is not fully understood, but
apoptosis (programmed cell death) and
molecular mimicry may play a role. Molecular and epidemiological studies suggest that anti-Sm antibodies may be induced by molecular mimicry because the protein shows some similarity to
Epstein-Barr virus proteins.
Anti-nRNP/anti-U1-RNP Anti-nuclear ribonucleoprotein (anti-nRNP) antibodies, also known as anti-U1-RNP antibodies, are found in 30–40% of SLE. They are often found with anti-Sm antibodies, but they may be associated with different clinical associations. In addition to SLE, these antibodies are highly associated with
mixed connective tissue disease. Anti-nRNP antibodies recognise the A and C core units of the snRNPs and because of this they primarily bind to the U1-snRNP. The immune response to RNP may be caused by the presentation of the nuclear components on the cell membrane in apoptotic blebs. Molecular mimicry has also been suggested as a possible mechanism for the production of antibodies to these proteins because of similarity between U1-RNP polypeptides and Epstein-Barr virus polypeptides.
Anti-Scl-70/anti-topoisomerase I Anti-Scl-70 antibodies are linked to
scleroderma. The sensitivity of the antibodies for scleroderma is approximately 34%, but is higher for cases with diffuse cutaneous involvement (40%), and lower for limited cutaneous involvement (10%). The specificity of the antibodies is 98% and 99.6% in other rheumatic diseases and normal individuals, respectively. In addition to scleroderma, these antibodies are found in approximately 5% of individuals with SLE. The antigenic target of anti-Scl-70 antibodies is
topoisomerase I.
Anti-Jo-1 Although anti-Jo-1 antibodies are often included with ANAs, they are actually antibodies to the cytoplasmic protein,
Histidyl-tRNA synthetase – an aminoacyl-tRNA synthetase essential for the synthesis of histidine loaded tRNA.
Anti-dsDNA Anti-double stranded DNA (anti-dsDNA) antibodies are highly associated with SLE. They are a very
specific marker for the disease, with some studies quoting nearly 100%. It is also possible that the anti-dsDNA antibodies are internalised by cells when they bind membrane antigens and then are displayed on the cell surface. This could promote inflammatory responses by T-cells within the kidney. It is important to note that not all anti-dsDNA antibodies are associated with lupus nephritis and that other factors can cause this symptom in their absence. The antigen of anti-dsDNA antibodies is
double stranded DNA.
Anti-histone antibodies Anti-histone antibodies are found in the serum of up to 75–95% of people with
drug-induced lupus and 75% of idiopathic SLE. Unlike anti-dsDNA antibodies in SLE, these antibodies do not fix complement. Although they are most commonly found in drug induced lupus, they are also found in some cases of SLE,
scleroderma,
rheumatoid arthritis and
undifferentiated connective tissue disease. Many drugs are known to cause drug induced lupus and they produce various antigenic targets within the nucleosome that are often cross reactive with several histone proteins and DNA.
Procainamide causes a form of drug-induced lupus that produces antibodies to the histone H2A and H2B complex.
Anti-gp210 and anti-p62 Both
anti-glycoprotein-210 (anti-gp210) and
anti-nucleoporin 62 (anti-p62) antibodies are antibodies to components of the nuclear membrane and are found in
primary biliary cirrhosis (PBC). Each antibody is present in approximately 25–30% of PBC. The antigens of both antibodies are constituents of the
nuclear membrane. gp210 is a 200kDa protein involved in anchoring components of the
nuclear pore to the nuclear membrane. The p62 antigen is a 60kDa nuclear pore complex.
Anti-centromere antibodies staining pattern of anti-centromere antibodies on HEp-20-10 cells
Anti-centromere antibodies are associated with limited cutaneous systemic sclerosis, also known as
CREST syndrome, primary biliary cirrhosis and proximal scleroderma. There are six known antigens, which are all associated with the
centromere; CENP-A to CENP-F. CENP-A is a 17kDa
histone H3-like protein. CENP-B is an 80kDa DNA binding protein involved in the folding of
heterochromatin. CENP-C is a 140kDa protein involved in
kinetochore assembly. CENP-D is a 50kDa protein of unknown function, but may be
homologous to another protein involved in
chromatin condensation,
RCC1. CENP-E is a 312kDa protein from the
kinesin motor protein family. CENP-F is a 367kDa protein from the nuclear matrix that associates with the kinetochore in late
G2 phase during mitosis. CENP-A, B and C antibodies are most commonly found (16–42% of systemic sclerosis) and are associated with Raynaud's phenomenon,
telangiectasias, lung involvement and early onset in systemic sclerosis. Anti-centromere antibodies are found in approximately 60% of patients with limited systemic scleroderma and in 15% of those with the diffuse form of scleroderma. The specificity of this test is >98%. Thus, a positive anti-centromere antibody finding is strongly suggestive of limited systemic scleroderma. Anti-centromere antibodies present early in the course of disease and are notably predictive of limited cutaneous involvement and a decreased likelihood of aggressive internal organ involvement, such as
fibrosis in the lungs. When present in
primary biliary cirrhosis, ACAs are prognostic of portal hypertension such that serum ACA levels correlate with the severity of portal hypertension.
Anti-sp100 Anti-sp100 antibodies are found in approximately 20–30% of
primary biliary cirrhosis (PBC). They are found in few individuals without PBC, and therefore are a very specific marker of the disease. The sp100 antigen is found within nuclear bodies; large protein complexes in the nucleus that may have a role in cell growth and differentiation.
Anti-PM-Scl Anti-PM-Scl antibodies are found in up to 50% of
polymyositis/systemic sclerosis (PM/SSc) overlap syndrome. Around 80% of individuals with antibodies present in their blood serum will have the disorder. The presence of the antibodies is linked to limited cutaneous involvement of PM/SSc overlap syndrome. The antigenic targets of the antibodies are components of the
RNA-processing
exosome complex in the
nucleolus.
Anti-DFS70 antibodies Anti-DFS70 antibodies generate a dense fine speckled pattern in indirect immunofluorescence and are found in normals and in various conditions, but are not associated with a systemic autoimmune pathology. Therefore, they can be used to help to rule out such conditions in ANA positive individuals. A significant number of patients are diagnosed as systemic lupus erythematosus or undifferentiated connective tissue disease largely based on a positive ANA. In case no defined autoantibody can be detected (e.g. anti-ENA antibodies), the testing of anti-DFS70 antibodies is recommended to verify the diagnosis. Anti-DFS70 antibody tests are available as CE-marked tests. Until now, no FDA cleared assay is available. ==ANA test==