Serum autoantibody testing in suspected autoimmune disease

Autoantibodies are antibodies directed against the body's own tissues (self-antigens). In many autoimmune diseases they circulate in the blood, so the usual way to look for them is to test serum, the clear fluid left after blood has clotted. The result shows which autoantibodies are present and can point to a specific disease.

Fatigue and joint pain together with a photosensitive rash, meaning a rash made worse by sunlight, suggest systemic lupus erythematosus (SLE), an autoimmune disease affecting many organs. The usual first step is the antinuclear antibody (ANA) test, which looks for antibodies against components of the cell nucleus. It is very sensitive, so a negative result makes lupus unlikely, but it is not specific: it can be positive in other conditions and in some healthy people. A positive result is therefore followed by more specific tests, such as anti-double-stranded DNA and anti-Smith antibodies.

Serum testing has an important limit. Not all autoimmune diseases have detectable circulating antibodies, and some antibodies are mainly tissue-bound, which means they stay in the organ. A local biopsy can then help, especially in organ-specific disease (disease affecting one or a few organs rather than many). For example, in Goodpasture disease the autoantibodies target the basement membrane, the thin supporting layer in the kidney filters and lung air sacs, and can be detected in serum, with renal biopsy a useful addition.