Chris Hartlove

Science of the Sexes (continued)

Sex differences were not a part of John Aucott’s original research plan when he set out three years ago to study the natural history of Lyme disease. In his field, there was no precedent for separating out male cases and female cases. It simply hadn’t occurred to him, a Hopkins-trained physician and fellow in infectious disease, that sex had anything to do with his patients’ biological reactions to a tiny tick bite.

Aucott is the go-to guy in the Mid-Atlantic region for Lyme patients with chronic post-treatment issues. Considering that Lyme is an emerged epidemic, and he’s based at its epicenter, Aucott is busy. A steady stream of acutely ill patients sporting telltale rashes show up daily at the urgent care center next door to his office in suburban Baltimore. From their ranks, he recruits study subjects “by the gobs.” Already he’s beginning to glean valuable information about the “normal” human immune response to an acute infectious disease over time.

“Pretending sex differences don’t exist is just going to obscure the real mechanisms we’re all trying to find.” —OraLee Branch

“Actually, we’re going to get a two-fer,” Aucott enthuses. “We are going to describe the normal human response in men and in women. It can’t be the same. Why would it be? I’m convinced of that now. I’m a believer.”

Aucott credits his conversion to study coordinator Alison Rebman. It was her key observations that led to finding differences in antibody responses between men and women—and, ultimately, to Sabra Klein.  About a year ago, she noticed significant trends that appeared to vary by sex and wondered if anyone had ever looked at sex differences and Lyme before, so she dug into the scientific literature. “I came across a review Sabra Klein had written about viral infection, and then a chapter of her book. I kept coming across her name, and after reading a few more articles, realized she’s at Hopkins!” Rebman says.

She contacted Klein, whose excitement about their Lyme findings was, well, infectious. “Sabra talked about how the female immune system is designed differently than a male’s,” Aucott says. “It has to do with all these crazy immunologic maneuvers to tolerate being pregnant. She’s helping us to think about how to design our study and how to analyze the data.”

Rebman’s initial discovery—that sex may affect the antibody response measured by the diagnostic test—landed her and Aucott in unexplored territory. It was known that the standard test for Lyme is not very sensitive, and apparently it may be even less so for women. Possibly, many, many more women go undiagnosed than ever suspected.

People who don’t get treated are known to develop months or years later a condition characterized by big swollen knees; it’s known as late Lyme arthritis, and twice as many men get it as women, according to Aucott.

“We know that equal numbers of men and women get Lyme to begin with, and twice as many men get late Lyme arthritis, so what happened to all the women?” Aucott asks. “Did they all just get better without treatment?”

He thinks not. Rather, he speculates that maybe the women who didn’t make enough antibodies to fit the diagnostic criteria for Lyme in the first place ended up getting diagnosed with something else: fibromyalgia, for instance.

Anecdotal information, now backed up by sex-based biology, informs his hunch: Acute Lyme disease is easily treated with an antibiotic. The rash and other symptoms disappear. However, 20 percent of people post-treatment—the majority of them women—develop a fibromyalgia-like syndrome some months later. The overall ratio of women to men with fibromyalgia is 7:1.

Aucott sees lots of patients who report having felt fine before their bout with acute Lyme, then recover, only to develop a vague constellation of disabling symptoms some- time later. The majority of them are females.

“These are people who are told by their physicians that they are ‘just depressed,’” Rebman says. “Well if they weren’t depressed before the rash, there’s got to be more to it. That can’t be the end of the story.”