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Introduction to Autoimmunity Quiz

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According to the classical criteria for proving that a disease is autoimmune, which finding provides the strongest direct evidence?

A Serum autoantibodies are found in most patients and their titres correlate with disease activity
B Transfer of autoantibodies or autoreactive T cells reproduces the disease in a healthy host ✓
C The disease can be reproduced in an experimental animal after immunisation with the suspected self antigen
D The condition is more common in people who carry a particular HLA haplotype
E The disease improves after removal of circulating antibodies by plasma exchange

The answer is B: Transfer of autoantibodies or autoreactive T cells reproduces the disease in a healthy host

Explanation

Why B is correct

See Causes of Autoimmunity. Option B is correct. The classical framework for deciding that a disease is autoimmune goes back to Witebsky and was revisited by Rose and Bona. It lists three types of evidence: direct evidence, indirect evidence and circumstantial evidence. Direct evidence is the strongest: autoantibodies (antibodies against the body's own tissues) or autoreactive T cells (T cells that recognise self antigens) are shown to be pathogenic, meaning they actually cause disease, by transferring them to a healthy recipient who then develops the disease. This is called passive transfer. Indirect evidence comes from reproducing the disease in an experimental animal by immunising it with the self antigen, and circumstantial evidence comes from clinical clues. The criteria are used to confirm a causal role of an immune response, so they are stricter than simply finding an autoantibody, because some autoantibodies, such as ANA, are also found in people without the disease.

Direct evidence: autoantibodies or autoreactive T cells are shown to be pathogenic.
Passive transfer: moving them to a healthy recipient who then develops the disease.
Other evidence: indirect evidence comes from immunising an animal with the self antigen, and circumstantial evidence from clinical clues.

Why the other options are incorrect

A. Serum autoantibodies are found in most patients and their titres correlate with disease activity: Autoantibodies are often found in healthy people and can be present without causing disease. Their presence, even at high titre, is circumstantial rather than direct proof that the immune response causes the tissue damage.
C. The disease can be reproduced in an experimental animal after immunisation with the suspected self antigen: Reproducing the disease by immunising an animal with the self antigen is classed as indirect evidence. It supports autoimmunity but is not as strong as transferring pathogenic cells or antibodies to a healthy host.
D. The condition is more common in people who carry a particular HLA haplotype: An HLA association supports a genetic susceptibility but does not directly prove that autoantibodies or autoreactive T cells cause the disease. It is circumstantial rather than direct evidence.
E. The disease improves after removal of circulating antibodies by plasma exchange: A response to plasma exchange suggests a role for antibodies but does not show that the transferred immune factor causes disease. It is therefore not the strongest direct evidence.

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1
Which finding most strongly supports a genetic contribution to the development of autoimmune disease?
2
A 24-year-old woman with known myasthenia gravis develops worsening muscle weakness affecting swallowing despite standard symptomatic treatment. Which management strategy is most appropriate for this acute deterioration?

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