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Autoantibodies against intracellular proteins have been detected in some autoimmune diseases (For example, TRIM21 in Sjögren's syndrome and NALP5 in Autoimmune Polyendocrine Syndrome Type 1).

My question is are these autoantibodies functional (e.g. play certain roles in the diseases) or are they just the byproducts of pathological processes?

Regarding the first case scenario, it is highly unlikely that these autoantibodies can penetrate the cell membrane to interact with the intracellular autoantigens.

The second case scenario sounds more probable to me. For example, some processes may cause cell death and lysis, thus release intracellular proteins. Local inflammation can co-occur and may trigger the formation of autoantibodies.

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    $\begingroup$ This review sketches out some of the scenarios from the point of view of cancer therapy. Some of them are unlikely, though I wouldn't say impossible, to happen naturally, but others are likely to be relevant. $\endgroup$
    – Mike Serfas
    Jul 1, 2021 at 0:19
  • $\begingroup$ @MikeSerfas Thank you. The third possibility "Antibodies can also be generated that bind cell surface major histocompatibility complex class I (MHC-I)-presented peptides that are derived from intracellular proteins." is brilliant. I should have thought of it. $\endgroup$
    – Josuke
    Jul 4, 2021 at 2:26
  • $\begingroup$ Thus your question "are these autoantibodies functional" is to be answered to the positive: yes, cells presenting these antigens are led to apoptosis by T cytotocic cells? Just to make sure. $\endgroup$
    – Peter Bernhard
    Oct 31, 2021 at 19:27

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