This week’s New England Journal of Medicine hooks up a strange pair of AIDS-related bedfellows. Just a few pages apart, the editors published two articles that seem to be pointing in opposite directions. First is a “Yes, We Can!”-style pep talk of an essay titled, peppily enough, “The Beginning of the End of AIDS?” This sure sounds like good news. But then just a few articles later comes an eerie report of a strange new immunodeficiency—the word that provides the “I” in AIDS—among adults in Thailand and Taiwan.
The latter article is a real page-turner, that is if you’re an academic immunologist, an Asian health specialist, or someone who likes to have the crap scared out of you. Along those last lines, the press sure is excited, smelling a hot late-summer story, and so too is the large group of people who love, just love, a ripping new epidemic.
But despite the headlines, one thing the new syndrome most assuredly is not is the first footfall of a new global health calamity, some sort of AIDS 2.0. Though AIDS and the new syndrome share a few things—broken immune systems resulting in a scorecard of oddball, make that really oddball, infections—the diseases otherwise have nothing more in common than influenza does with getting injured in a car wreck. Both events can make you sick and even kill you, both are miserable and unhappy-making, but the buck stops there.
That said, make no mistake—the Thai-Taiwanese syndrome is altogether new and still incompletely worked out. The story is a classic of doggedness, cleverness, and a little luck. Working with researchers from the U.S. National Institutes of Health (NIH), local investigators noticed a series of unusual cases and soon accumulated 200 patients with “opportunistic infections,” so called because they exploit the limitations of a clumsy or entirely absent immune system, such as occurs in people with advanced AIDS or those wobbling through the early days after a bone marrow transplant.
In contrast, the Asian patients had no such underlying conditions. They were otherwise relatively well-appearing adults of all stripes, unrelated to each other, not neighbors, not friends, not co-workers, not drug users, and not sexual partners. They had gone a good 40 or 50 years of adult life without a whiff of trouble. Yet here they were, with skin infections growing strange fungi, unusual lumps caused by even less common bacteria, or persistent salmonella that could not be vanquished—the array of problems clinicians had learned to associate with HIV infection.
The first difference was this: their CD4 cells, also called T-cells or T4 cells, were normal. Since AIDS first was described, the CD4 cell count has been the clinical signpost that guided doctors and patients. A low count spelled serious trouble, whereas high and stable numbers were seen in those with a good response to antiviral drugs. The normal CD4 cell count in the patients from Asia meant the investigators had to dig even deeper to understand the problem, and that thankfully we were not dealing with AIDS 2.0.
With an enormous amount of work, they found that many of the patients had an unexplained destruction of a chemical crucial to the immune response. Every normal person’s white blood cells pump out something called gamma-interferon as they move in for the kill. The patients from Asia seemed to do this just fine. However, they also made antibodies, referred to as auto-antibodies, that neutralized their own just-made gamma-interferon, leaving them without a drop of the necessary juice. Because of this gamma-interferon shortage, the CD4 and other inflammatory cells were ready and willing to kill the pathogen but were completely unable.
The idea someone can produce auto-antibodies against parts of his own body is a key concept in many previously described “auto-immune” diseases as lupus, types of thyroid inflammation, ulcerative colitis, and rheumatoid arthritis. For altogether unexplained reasons, in these conditions, the person’s own immune system goes rogue and begins to attack his own joints or blood vessels, nature’s most literal example of self-destruction behavior. It may be that this new group of Asian patients will fit loosely under the big tent of these related conditions, or the syndrome may be telling us something altogether new about the human immune system.
With this report, much remains unanswered: why these patients in this part of the world right now? Were they always around but we lacked the tests to diagnose them or did something new happen? The New England Journal article surely is the first of many to come as the investigators further explore the anti-interferon antibody in these patients, and others with possibly related conditions. In every way it is a work in progress. Let’s hope the new syndrome’s accidental proximity to the hothouse world of HIV, with its attendant urgency and rush, will not cause collateral damage by pressuring the researchers who are busily excavating the story to hurry up already. Rather, they need to be afforded sufficient space and time to get the facts right.