From time to time, I get questions regarding the connection between hypersensitivity reactions and autoimmune diseases. We discuss them one after the other in class – so it makes sense to try to sort out how they are related. Here are a couple recent questions:

Q. My question is: which of the four hypersensitivity reactions are considered “autoimmune” disorders?

Q. I am studying for boards and I am wondering: is Sjögren syndrome classified as one of the hypersensitivity reactions?

A. I think that the answer to these questions is kind of about semantics – about naming and defining things.

It’s true that many autoimmune diseases have a hypersensitivity reaction as part (or all) of their pathogenesis. For example:

• Lupus is caused (at least in part) by a type III (immune complex) hypersensitivity reaction.
• Graves disease is caused by a type II (antibody-mediated) hypersensitivity reaction.
• Autoimmune hemolytic anemia (warm and cold) has a type II hypersensitivity thing going on.
• Type I diabetes mellitus involves a type IV hypersensitivity reaction.

In fact, all of the hypersensitivity reactions can play a role in autoimmune diseases except type I hypersensitivity (which is the mechanism involved in regular old allergies).

However, although hypersensitivity reactions and autoimmune diseases overlap, they are not the same thing. For one thing, hypersensitivity reactions in and of themselves aren’t really autoimmune diseases – they are really just mechanisms (not specific diseases).

Not all hypersensitivity reactions are linked to an autoimmune disease either (type I hypersensitivity, as stated above, is not involved in autoimmune diseases). Further, not all autoimmune diseases are caused by a known hypersensitivity reaction; sometimes the underlying mechanism is a mystery.

A good example of an autoimmune disease with a mysterious cause is Sjögren syndrome. It may be caused by mechanisms that resemble a couple of the hypersensitivity reactions – but really, nobody knows.

Here’s what Robbins says about the cause of Sjögren syndrome:

“Although the pathogenesis of Sjögren syndrome remains obscure, aberrant T-cell and B-cell activation are both implicated. The initiating trigger may be a viral infection of the salivary glands, which causes local cell death and release of tissue self-antigens. In genetically susceptible individuals, CD4+ T cells and B cells specific for these self-antigens may have escaped tolerance and are able to react. The result is inflammation, tissue damage, and, eventually, fibrosis. The nature of the autoantigen(s) recognized by these lymphocytes is still mysterious.” (page 229)

So, bottom line: hypersensitivity reactions are mechanisms that describe how the body reacts (or over-reacts) to certain stimuli. Autoimmune diseases are characterized by the body attacking itself. Many (but not all) of the autoimmune diseases have a hypersensitivity reaction as part of their pathogenesis; and most (but not all) hypersensitivity reactions are manifested in several of autoimmune disorders.