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Could the overactive immune response behind psoriasis have helped ancestors survive the Black Death? A look at ancient DNA, immune genes, and the evidence for and against.
Psoriasis is a chronic immune-mediated skin disease in which an overactive immune response drives thick, scaly plaques. It is usually discussed as a burden: itch, visible lesions, joint involvement and links to heart and metabolic disease. Evolutionary biology asks a different question. If psoriasis is so common and so strongly inherited, could the same immune vigour that inflames the skin once have helped ancestors survive the great epidemics, including the plague? This article examines what the genetic evidence supports, where it falls short, and what it means for people living with psoriasis today.
Between 1346 and 1350, the first outbreak of the second plague pandemic, known as the Black Death, swept across Afro-Eurasia. It was caused by the bacterium Yersinia pestis and killed up to 30 to 50 percent of the population, making it the single greatest mortality event in recorded history [1]. Plague is usually transmitted by the bite of an infected flea. The bacteria enter through the skin, travel to the nearest lymph nodes and produce the swollen, painful buboes that gave bubonic plague its name.
An event of that scale acts as a powerful evolutionary filter. If certain inherited immune variants improved the odds of surviving infection, those variants would be expected to become more common in the generations that followed. Because victims were buried in dated plague pits and cemeteries, ancient DNA offers a rare opportunity to test that idea directly rather than only theorize about it.
In 2022, an international team led by researchers at McMaster University in Hamilton, Ontario, and the University of Chicago analyzed immune-related genes in 206 ancient DNA extracts from London and Denmark. The samples came from individuals who died before, during and after the Black Death [1]. Immune genes showed more pronounced shifts in frequency across the pandemic than a comparison set of non-immune genes, a pattern the authors interpreted as a sign of positive natural selection.
The strongest candidate was a variant called rs2549794 near the gene ERAP2. The favoured version of this variant is associated with production of a full-length ERAP2 transcript, a different cytokine response to Y. pestis, and a greater ability of immune cells called macrophages to control the bacterium in laboratory experiments [1]. ERAP2 is an enzyme that trims protein fragments before they are displayed on HLA molecules, the cell-surface identity tags that allow T cells to recognize infected cells.
The trade-off: The same study reported that variants that appeared protective during the plague overlap with alleles that are associated today with increased susceptibility to autoimmune diseases [1]. Put simply, an immune system tuned to fight a deadly bacterium may be more prone to attacking the body's own tissues once that bacterium has largely disappeared.
Psoriasis is one of the clearest examples of a disease driven by an overactive immune response. Its best-known genetic risk factor is a variant of the HLA-C gene. A large genome-wide association study published in 2010 showed that variants in ERAP1, the neighbouring gene and close functional relative of ERAP2, influence psoriasis risk only in individuals who carry the HLA-C risk allele [2]. Both enzymes belong to the same peptide-processing pathway, so the plague findings and the psoriasis findings point to the same part of the immune machinery.
This does not mean that the ERAP2 plague variant causes psoriasis. It does mean that the genetics of psoriasis and the genetics of fighting infection overlap closely enough for the evolutionary question to be a reasonable one to ask.
One of the earliest clues came from the skin itself. In 1997, researchers in Kiel, Germany, isolated a previously unknown antimicrobial peptide, human beta-defensin-2, from psoriatic scales [3]. Antimicrobial peptides are small natural antibiotics produced by skin cells, and psoriatic plaques contain them in large amounts. An earlier analysis of more than 40,000 patients from the same centre had noted increased resistance to cutaneous bacterial infections in people with early-onset psoriasis, and the authors suggested that this pattern pointed to genetically determined selection [4].
Plague is not the only infection proposed as a selective force. A 2012 study of 1,727 people with psoriasis and 3,581 controls found that psoriasis patients were significantly more likely to carry HLA and natural killer cell gene variants associated with control of HIV-1 [5]. The authors concluded that genetic variants contributing to antiviral immunity may predispose to psoriasis.
Dermatologists in Greece have proposed a similar story for leprosy. Based on the clinical observation that psoriasis and leprosy are almost mutually exclusive, they suggested that resistance to leprosy may have favoured the spread of some psoriasis-associated genotypes in the ancestors of modern Europeans [6]. This proposal was published as a hypothesis, and the authors themselves called for genetic and paleoepidemiological studies to test it.
Answering the question directly requires honesty about what the data can and cannot show. No study has identified medieval individuals with psoriasis and compared their plague survival with that of their neighbours. The argument is indirect: it rests on shared genes and shared immune pathways rather than on observed outcomes.
What is plausible: A person carrying some of the immune variants common in psoriasis may have mounted a faster and more forceful early response to Y. pestis. Since bubonic plague begins with a flea bite in the skin, a barrier already rich in antimicrobial peptides is an intriguing, though untested, advantage.
What is contested: In 2025, a separate group of geneticists re-analyzed the Black Death data and argued that the evidence for selection was insufficient. They reported that the enrichment signal disappeared under appropriate randomization testing, identified a technical error in allele frequency estimation, and found that the filtering thresholds did not adequately correct for multiple testing [7]. The original authors responded with a reanalysis of their data [8]. The debate is unresolved: it remains plausible that immune genes were under selection during the Black Death, but how strong that selection was, and which genes were affected, is still uncertain.
What mattered most: Even under the most optimistic reading, a genetic advantage shifts the odds modestly; it does not make anyone immune. Exposure, crowding, nutrition and general health would have weighed at least as heavily as any single gene variant. A person with psoriasis in 1348 might have had slightly better odds, but nobody had a guarantee.
Natural selection does not favour comfort or longevity; it favours whatever helps people survive long enough to raise children. A variant that protects against a sudden epidemic can persist even if it causes chronic inflammation decades later. This delicate balance between variants that boost control of infection and variants that raise the risk of autoimmune disease is a recognized paradigm in evolutionary genetics [5], and it helps explain why immune-mediated diseases remain so common.
For people with psoriasis, the cost is visible: skin plaques and, for some, inflammation that extends to the joints as psoriatic arthritis. The Kiel analysis also found that diabetes, heart insufficiency and obesity occurred significantly more often in people with psoriasis than in controls [4]. Chronic, low-grade inflammation is now understood to contribute to many of these conditions, a theme explored further in Inflammaging: Are We Aging Properly?.
An inherited immune profile, not a personal failing. Psoriasis is not contagious and is not caused by poor hygiene. Many of the genes involved belong to the same immune toolkit that helped human populations withstand infections over thousands of years.
Targeted treatment works with the biology. Modern therapy does not need to suppress the entire immune system. Biologic and advanced small molecule therapy blocks specific signals, such as interleukin-17 and interleukin-23, that drive plaque formation. Treatment choices, including screening for latent infections before therapy, are individualized.
Measure and monitor. Disease severity is tracked with validated tools such as the Psoriasis Area and Severity Index (PASI), which helps determine when a treatment plan needs to change.
Seek assessment early. People with persistent scaly plaques, nail changes or joint pain can request a consultation at the Centre for Medical and Surgical Dermatology, where psoriasis is managed through the Immune-Mediated Skin Disease Clinic.
Would a person with psoriasis have survived the Black Death? The honest answer is that nobody knows. The idea that psoriatic plaques are an echo of an immune system shaped by ancient epidemics is biologically plausible and partly supported by genetics, but the plague-specific evidence remains contested. What is certain is that an immune response which may once have been an asset now calls for careful, evidence-based management, and effective treatments are available.
This article is intended for educational purposes and does not replace professional medical advice. Please consult your dermatologist for personalized recommendations.
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