Anti-nuclear antibodies (ANA)

Anti-nuclear antibodies (ANA):
Anti-nuclear antibodies are autoimmune antibodies that attack a person’s own system. In biology it always seems as if every iteration exists somewhere, and in the case of antinuclear antibodies, no part of the nucleus is off limits for an attack.

The most common condition associated with anti-nuclear antibody testing is systemic lupus erythematosus (SLE). Different conditions associate with specific autoantibodies, and SLE is associated with anti-double stranded DNA (anti-ds DNA).

The screening test of choice for SLE and many other autoimmune conditions is fluorescent nuclear antibody testing (FANA). In FANA, patient serum is reacted with a reagent epithelial cell line (HEp-2 is a common cell line used). After washing away excess unbound antibody from the patient serum, antihuman globulin with a fluorescent tag is added. The sample is then viewed under the fluorescent scope. FANA testing is very sensitive but not highly specific. For example, FANA testing will miss cases of SLE as well as call about 2% of people with no SLE positive.

There is another less frequently used SLE test to be aware of that involves the parasite Crithidia luciliae. Crithidia luciliae contains a structure called a kinetoplast which is a mitochondrial structure that houses DNA. In the case of Crithidia luciliae it houses a lot of circular ds-DNA. A similar fluorescent test as the one outlined above can be used with Crithidia luciliae. This test is more specific but less sensitive than FANA.

Nerdy note
The most common host of Crithidia luciliae is the house fly, so next time you’re swinging at one with your fly swatter, remember there may be Crithidia luciliae inside!

There are a few specific ANA patterns and associations the clinical lab scientist needs to be aware of, they are outlined in the table below.

ANA Pattern	Autoantibody	Disease Association
Homogenous/Peripheral Rim	Anti-ds-DNA	SLE
Homogenous	Anti-histone	Drug induced lupus
Speckled	Anti-Smith (Anti-Sm)	SLE
Speckled	Anti-SS-A, Anti-SS-B	SLE and Sjogren’s Syndrome
Speckled	Anti-Scl-70	Scleroderma
Speckled	Anti-centromere	CREST syndrome

A few quick notes. Anti-Sm antibodies are antibodies to extractable nuclear antigens associated with uridine-rich RNA. Anti-Sm antibodies are specific for SLE but are only found in a small percentage of people with SLE.

SS-A and SS-B are also extractable nuclear antigens. SS-A is RNA complexed to one of two proteins, and SS-B is a phosphoprotein bound to an RNA polymerase.

Scl-70 is a DNA topoisomerase 1, which is involved with DNA assembly and disassembly.