ORGANUM
The antinuclear antibody (ANA) is a defining feature of autoimmune connective tissue disease. ANAs are a class of antibodies that bind to cellular components in the nucleus, including proteins, DNA, RNA, and nucleic acid-protein complexes. First described in 1948, ANA identification has been the foundation of diagnosis for autoimmune connective tissue diseases such as:
SLE
Sjogren's syndrome
Polymyositis/dermatomyositis
20-30% of the population has detectable levels of ANAs, increased titers are characteristic of individuals with connective tissue disorders - this means the sensitivity and specificity of the methods used to detect ANAs are crucial to diagnosis.
ANAs refer to an autoantibody directed at material within the nucleus of a cell. ANAs are classed into two groups:
Antibodies to DNA and histones
Antibodies to nuclear material
Antibodies directed to DNA and histones
anti-dsDNA
anti-histone
Antibodies directed to nuclear antigen
anti-Smith
anti-SSA/Ro
anti-SSB/La
anti-U3-RNP
anti-centromere
Scl-70
Jo-1
ANAs bind to various molecular compounds with the cell's nucleus, including nucleic material and proteins.
Antibodies may bind to double-stranded DNA (anti-dsDNA), and studies suggest that antibodies are formed during the incomplete removal of cellular material during apoptosis.
anti-Sm antibodies bind to the Smith protein, a protein contained within small nuclear ribonucleoprotein (snRNP) particles.
Scl-70 antibodies interfere with DNA replication by binding to Topoisomerase I
anti-centromere antibodies affect cell division by binding to centromeres during interphase
Jo-1 antibodies prevent histidine binding to tRNA during protein synthesis by targeting histidyl-tRNA synthetase.
Ro/SSA is an antigen that is an amino acid sequence that binds to double-stranded and single-stranded DNA. The suspected mechanism is that they may bind to viral DNA of EBV with molecular mimicry, later causing autoimmune disease. Anti-Ro can pass the placenta and cause neonatal lupus/heart block.
La/SSB is a protein found primarily in the nucleus. Similar to Ro, La is also known to bind nuclear material from EBV
Systemic autoimmune disorders affect 3-5% of the population, and ANAs are one of the few specific disease markers in their diagnosis. ANA testing is often the first step in diagnosing systemic autoimmune connective tissue disorders. However, they do not necessarily confirm that an individual has or will develop an autoimmune disease. Although positive ANA results help diagnose several autoimmune disorders, the negative ANA titer is also expected in some specific inflammatory conditions such as ankylosing spondylitis.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects nearly every system in the body. Clinical manifestations may include fatigue, arthritis, vasculitis, nephritis, pleuritis, and myocarditis. Clinical manifestations and immunologic criterias are required to establish a definitive diagnosis of SLE. Immunologic criteria include abnormal ANA titers in the absence of drugs and the presence of anti-dsDNA/anti-Sm antibodies.
Scleroderma, or systemic sclerosis, involves progressive fibrosis of the skin and organs. It either presents as a limited form or a diffuse cutaneous form. Diagnostic basis is a combination of clinical symptoms and increased ANA tiers. Scl-70 is highly correlated with scleroderma, while anti-centromere antibodies are moderately correlated.
Polymyositis (PM) and dermatomyositis (DM) are a group of inflammatory disorders that primarily affect the proximal muscles and cause inflammation. The primary clinical manifestation of PM is the gradual weakening of the proximal muscles. Likewise, DM present with gradually increasing proximal weakness. Cutaneous symptoms such as facial erythema, poikiloderma in sun-exposed areas, and Gottron's papules on the extensor surface of the hands are present. General ANA testing is used to diagnose PM and DM, while anti-Jo1 antibodies are associated with 30% of patients with PM/DM.
Sjogren's syndrome is a chronic autoimmune pathology that destroy the exocrine glands, including the lacrimal and salivary glands. Diagnosis centers on clinical manifestations and serologic testing. Clinical manifestations include chronic dry eye, dry mouth, Raynaud's phenomenon, arthritis and bronchitis. When there is a suspicion of SJogren's syndrome, testing for anti-Ro/SSA and anti-La/SSB is the protocol.
Psoriatic arthritis is a subtype of inflammatory arthritis that is seen in association with psoriasis (which is a member of the spondyloarthritis family). The condition can present with relatively subtle signs. ANA testing has long thought to be a diagnostic tool and a potentially detectable serum marker to enhance clinical recognition of the condition. A study in 2015 found an increase in serum ANA in patients with PA compared to healthy controls. Of note, the cohort under investigation excluded other confounding conditions that may cause positive ANA such as RA.