Lupus Sex Differences Are Not What You Might Think

This is Dr. Seyhan Yazar, a medical scientist and Research Fellow, whose lab (the Yazar Lab) “focuses on uncovering the complex interplay between genetic susceptibility and environmental triggers in autoimmune diseases”, of which, lupus is one.

So, what does she want us to know?

Sex? It’s not about the X

First, a recap on how lupus works: lupus is an autoimmune disease where the immune system attacks its own tissues, causing inflammation and organ damage (to oversimplify it in very few words).

Next, how lupus is currently treated: mostly with immunosuppressant drugs, which reduce symptoms but have significant side effects, not least of all the fact that your immune system will be suppressed, leaving you vulnerable to infections, cancer, aging, and the like. So, there’s really a “damned if you do, damned if you don’t” aspect here (because untreated lupus will run your immune system into the ground with its chronic inflammation, which will also leave you vulnerable to the aforementioned things).

See also: How to Prevent (or Reduce) Inflammation

Finally, onto the new science from Dr. Yazar: while it’s well-known that lupus disproportionately affects women (with women’s lupus risk being 9x that of men’s, all other things being equal), it hasn’t been known entirely what’s going on with that and how, but Dr. Yazar’s work shines new light on this!

She and her team analyzed over a million (for the curious: 1,267,758) individual immune cells from 982 healthy people, to identify sex-specific genetic switches that shape male and female immune systems differently.

In the immune cell analysis, women had higher levels of B cells and regulatory T cells, with immune activity more strongly biased towards inflammatory pathways, creating a more vigilant immune system that will often better fight infections, but at a cost: it also raises the risk of “friendly fire” against healthy tissues, and that’s what happens in the case of lupus.

On the flipside, men had more monocytes and immune activity focused more on cellular maintenance rather than inflammation, which will tend to reduce autoimmune risk but at its own cost: it raises the risk (and severity) of infections and some cancers.

Notably, these results showed that the sex-specific immune differences aren’t driven by X or Y chromosomes as often assumed, but instead by autosomes—the non-sex chromosomes shared by all sexes.

This is very consistent with what we know of many sex-related disease risk factors being hormonally mediated, rather than mediated by genes.

You can read Dr. Yazar’s paper on all of this, here: The impact of sex on the immune system explored at the single-cell level

As for what can be done about this, the same principle applies as we talked about in Alzheimer’s Sex Differences May Not Be What They Appear but the opposite way around, meaning the solution may be the same as what we talked about in The Hormone Therapy That Reduces Breast Cancer Risk & More.

But! That last part is not yet proven, and is rather more simply a promising avenue for the next leg of the research, so please don’t take that as medical advice.

Want to learn more?

For a much more in-depth treatment of lupus management, you might like this excellent book we reviewed a while back:

The Lupus Encyclopedia: A Comprehensive Guide For Patients & Healthcare Providers – by Dr. Donald Thomas et al.

The “et al.” in question? Jemima Albayda, MD; Divya Angra, MD; Alan N. Baer, MD; Sasha Bernatsky, MD, PhD; George Bertsias, MD, PhD; Ashira D. Blazer, MD; Ian Bruce, MD; Jill Buyon, MD; Yashaar Chaichian, MD; Maria Chou, MD; Sharon Christie, Esq; Angelique N. Collamer, MD; Ashté Collins, MD; Caitlin O. Cruz, MD; Mark M. Cruz, MD; Dana DiRenzo, MD; Jess D. Edison, MD; Titilola Falasinnu, PhD; Andrea Fava, MD; Cheri Frey, MD; Neda F. Gould, PhD; Nishant Gupta, MD; Sarthak Gupta, MD; Sarfaraz Hasni, MD; David Hunt, MD; Mariana J. Kaplan, MD; Alfred Kim, MD; Deborah Lyu Kim, DO; Rukmini Konatalapalli, MD; Fotios Koumpouras, MD; Vasileios C. Kyttaris, MD; Jerik Leung, MPH; Hector A. Medina, MD; Timothy Niewold, MD; Julie Nusbaum, MD; Ginette Okoye, MD; Sarah L. Patterson, MD; Ziv Paz, MD; Darryn Potosky, MD; Rachel C. Robbins, MD; Neha S. Shah, MD; Matthew A. Sherman, MD; Yevgeniy Sheyn, MD; Julia F. Simard, ScD; Jonathan Solomon, MD; Rodger Stitt, MD; George Stojan, MD; Sangeeta Sule, MD; Barbara Taylor, CPPM, CRHC; George Tsokos, MD; Ian Ward, MD; Emma Weeding, MD; Arthur Weinstein, MD; Sean A. Whelton, MD

The reason we mention this is to render it clear that this isn’t one man’s opinions (as happens with many books about certain topics), but rather, a panel of that many doctors all agreeing that this is correct and good, evidence-based, up-to-date (as of the publication of this latest revised edition all so recently) information.

Want to learn less?

If the aforementioned 848-page opus seems a little too overwhelming, then you might prefer:

The Lupus Solution – by Dr. Tiffany Caplan & Dr. Brent Caplan ← a much slimmer tome; just 182 pages 🙂

Take care!