Nature vs. Nurture & Their Roles in Autoimmunity

Note: This is a representative image and not the actual twins discussed here.

They looked exactly alike—tall, slightly scruffy gentlemen with denim overalls lightly stained with dirt and oil, with dusty trucker hats to match. The only difference was that one wore a red checkered shirt and the other wore a green one. Yet these similarities were deceptive. The one closest to me was the patient, the one who came into our clinic with swollen hands and wrists, as well as an impressively high rheumatoid factor and sedimentation rate. His twin apparently had no musculoskeletal issues at all. In fact, the patient—let’s call him Bob—said his hands had looked like his twin brother John’s only six months before.

The stories of patients like these absolutely fascinate me. Bob and John are identical twins, as if someone had hit copy and paste. And, as they mentioned, they had grown up in the same house in the same small Midwestern town, graduated from the same schools, worked in the same line of business, and even ate the same types of foods. And yet, Bob developed rheumatoid arthritis, but John had not experienced any symptoms to date. In fact, even a decade after Bob’s diagnosis, John continues to wait for his joints to start aching and swelling. We hope they never will.

Everyday mysteries like these are what originally drew me to rheumatology (and allergy/immunology). As a specialty, we tend to evenly divide the pathogenesis of our diseases into nature or nurture. But is this paradigm truly accurate? Let’s rheuminate!

Nature vs. Nurture?

Whether fairly or not, we assume that identical twins, sharing virtually all of their DNA, should also share identical destinies when it comes to their health. But clinical practice—and a growing body of research—reveals just how simplistic that assumption can be.¹ Bob and John are a case in point.

Despite their shared genome and nearly indistinguishable upbringings, their bodies told two very different immunologic stories.

This divergence highlights the rapidly evolving landscape of epigenetics—the study of how environmental exposures can switch genes on or off without altering the DNA sequence itself. If genetics provides predestined blueprints for an overarching structure, epigenetics fine-tunes this destiny to accommodate changes in fortune. One twin’s immune system, perhaps triggered by a respiratory infection, a shift in the microbiome or an occupational exposure, began expressing inflammatory genes in a way the other’s never did.