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Mistaken identity: Influenza/narcolepsy autoimmunity link confirmed

New research has confirmed that an antigen in some variants of the flu virus and vaccine can, in rare cases, trigger an autoimmune response leading to narcolepsy.

There's a theory in immunology, called the molecular mimicry hypothesis, that autoimmunity (where the immune system turns on the body's own tissues) is the result of mistaken identity: The immune system confuses a tiny chunk of a protein residing in a healthy person's body for a chunk of a protein found in an infectious microbial pathogen, then winds up attacking the tissue containing that protein instead of standing down as it should (and usually does).

But proving that theory requires identifying the piece of protein from the pathogen and the piece of protein from the person and then showing that each protein piece incites the same batch of immune cells to fire up, expand into an angry swarm, and direct a sustained attack by the entire immune system on the bodily protein wherever it can be found. Big order.

Until now, nobody's managed to showcase this entire process, step by step, for any of the numerous autoimmune disorders that plague humanity. This can be because the specific antigen (the piece of protein) from either the host or the pathogen (or both) hasn't been determined yet. Or it can be because of the daunting difficulty of fishing out, among the immensely complicated array of cells constituting the immune system, the particular set of so-called helper T cells responsible for the false alarm.

Helper T cells are immune cells tasked with recognizing foreign invaders and then roping myriad other immune-cell players into a coordinated assault on them. In principle, every helper T cell is primed to respond to one particular antigen (which it recognizes not only by the antigen's shape but also by other features such as its electronic-charge configuration) and only that antigen. But in the case of autoimmunity, according to the molecular-mimicry theory, an unfortunate strong resemblance between the "good guy" and "bad guy" antigens sometimes fools helper T cells into mounting an immune response against innocent tissue they've mistaken for a pathogen.

Now there's a proven precedent: A team led by Emmanuel Mignot, MD, PhD, has shown that the same set of helper T cells responds angrily to both an antigen from a viral protein and an antigen from the bodily protein that's destroyed by the immune system in the course of an autoimmune disease called narcolepsy.

Mignot has devoted much of his career to the study of narcolepsy, a rare and strange sleep disorder that affects 1 in 3,000 people. People with narcolepsy experience irresistible daytime drowsiness and frequent, sudden sleep attacks: intermittent, uncontrollable episodes of falling asleep throughout the day.

In a new study in Proceedings of the National Academy of Sciences, Mignot's team provides strong evidence confirming a theory Mignot has pursued since the global swine-flu pandemic of 2009-10: namely, that narcolepsy is an autoimmune disease, and that a trigger for it is an antigen not only found in swine flu (as well as in other versions of the "A" strain of influenza), but — alas — also included in the vaccine hastily developed and massively administered during the pandemic to protect people.

This possibility was suggested by an uptick in narcolepsy cases among patients receiving a version of the vaccine (there were two). Mignot's group believed they'd firmly established the connection in a study they published in 2013, but this study was later retracted at Mignot's urging when he found himself unable to reproduce results of crucial experiments conducted by a co-author.

In the new study, however, Mignot's team used a more-rigorous method to track down the specific set of helper T cells that, indeed, react strongly to both a protein found in the flu virus (and, more so, in the narcolepsy-inducing vaccine version) and a protein residing on key brain cells whose loss induces narcolepsy. The findings carry constructive implications for modifying flu vaccines to exclude autoimmunity-provoking antigens.

Meanwhile, keep this in mind: First, far more lives were saved by the swine-flu vaccine — even the version containing too much of the troublesome antigen — than were impaired by vaccine-induced narcolepsy.

Second, getting the flu is itself a risk factor for narcolepsy, and vaccination has been demonstrated to reduce both the frequency of influenza infection and, among  those who have been vaccinated but nonetheless contract the virus, its severity.

The moral of the story? Don't let worries about narcolepsy stop you from getting a flu vaccine.

Photo by K. Kendall

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