Find the Antigen(s), Define the Disease

*Postorgasmic illness syndrome

Searching for antibodies and antigens can determine whether a disease is autoimmune. In my last post, I briefly touched on theoretical, non-autoimmune mechanisms for Postorgasmic illness syndrome. In this post, I focus on what is known about antigens found specifically in semen. To recap, antigens are molecules on the outside or inside of a cell that antibodies react to. By definition, antibodies and antigens require each other. One cannot exist without the other. An antigen is usually a fully-functioning part of a cell, rather than just a molecule hanging around and waiting to be attacked by an antibody.

Prostate-Specific Antigen

Prostate-specific antigen is a known antigen that appears in semen. I could not find that it has been studied in the context of Postorgasmic illness syndrome. According to my literature search, it is mainly studied in the context of fertility and prostate cancer. Prostate-specific antigens are of interest in the context of Postorgasmic illness syndrome because the first physician/scientist to describe Postorgasmic illness syndrome, and subsequently study it, Waldinger, published a 2016 report of a woman complaining of Postorgasmic illness syndrome. He then speculated that prostate-specific antigen in men and prostatic-type tissue in women, found in the upper wall of the vagina, might be what triggers Postorgasmic illness syndrome. This led me to wonder…

Are there other types of antigens that appear only in semen?

If sperm is removed, what other potentially antigenic structures does semen contain? I found a 2012 study conducted on 22 vasectomized men that defined how to find and differentiate some of the small fluid-filled sacs found in semen (pictured above). These sacs are encased in a membrane (membranes are notoriously antigenic) and called “membranous vesicles.” Some of these vesicles are called “prostasomes” because they’re created from the skin-type (epithelial) cells of the prostate. Theoretically,

Prostasomes have been proposed to perform a variety of functions, including modulation of (immune) cell activity within the female reproductive tract…How prostasomes mediate such diverse functions, however, remains unclear. In many studies, vesicles from the seminal plasma have been categorized collectively as a single population of prostasomes; in fact, they more likely represent a heterogeneous mixture of vesicles produced by different reproductive glands and secretory mechanisms.

(Aalberts et. al, 2012)

In my last post I explored how sperm-associated antigens (SPAGs) are known to be attacked by self-antibodies in the male reproductive tract. The Aalberts study found two distinct vesicle types with two distinct cell proteins that reacted with antibodies in a lab setting. Smaller vesicles contained a protein called GLIPR2. GLIPR2 is particularly expressed by leukocytes (white blood cells), linking it to immunity (possibly autoimmunity?). Larger vesicles were associated with a protein called annexin A1 on their cell surface. GLIPR2 and annexin A1 are known to modulate the female immune response against sperm. “Modulate” meaning to lower the female immune response. The loss of annexin A1 in prostate cancer cells correlates with cancer progression. There is no scientific evidence to suggest this, and I am a nurse, not a researcher, but it is possible that just as the presence of these antigens lowers an immune response, the absence of these antigens could increase an immune response.

Both the small and large vesicles also carried prostate-stem cell antigen (distinct from prostate-specific antigen) in some cases, which proved that both vesicle types originated from the prostate. CD9 molecules were present on all vesicles sampled. CD9 is the acronym for “Cluster of Differentiation” molecules and/or “Cluster of Designation” molecules. “CD” is used to name and study cell surface molecules for immunophenotyping of cells. Curiously, prostate stem cell antigen (PSCA) was absent from 9 out of 22 semen donors, indicating possible variation in originating source of vesicles. The authors also note that there may have been other antigenic structures that were unidentified in their lab process, and which they did not have available laboratory antibodies to test for.

Given that semen from vasectomized men was used as a source, membrane vesicles that are known to be produced by the epididymis (i.e., epididymosomes) [17] as well as any that may be generated within the testis or shed from the plasma membrane of (developing) sperm cells can be excluded. By contrast, the vesicular glands, terminal vas deferens, or bulbourethral glands may all contribute membrane PSCA-negative CD9-positive vesicles [4].

(Aalberts et. al, 2012)

Why it Matters

This is a lot of technical information about possible antigenic theories of Postorgasmic illness syndrome—and unfortunately none of it has been studied specifically in the context of Postorgasmic illness syndrome. Where I find a promising avenue of exploration is in what is already known about antigen/antibody interactions related to sperm and antigenic structures found just in semen. There’s also a published process for looking for antigenic membranous vesicles, identifying them, and differentiating them from each other. That’s important, because it means the same process can be done in a study population suffering from Postorgasmic illness syndrome. That population can be compared to a non-affected control group. An identified process for isolating and studying potentially antigenic structures is the basis for how Postorgasmic illness syndrome could be specifically studied and described.

References

Aalberts M, van Dissel-Emiliani FM, van Adrichem NP, van Wijnen M, Wauben MH, Stout TA, Stoorvogel W. Identification of distinct populations of prostasomes that differentially express prostate stem cell antigen, annexin A1, and GLIPR2 in humans. Biol Reprod. 2012 Mar 22;86(3):82. doi: 10.1095/biolreprod.111.095760. PMID: 22133690.

Waldinger MD, Meinardi MM, Schweitzer DH. Hyposensitization therapy with autologous semen in two Dutch caucasian males: beneficial effects in Postorgasmic Illness Syndrome (POIS; Part 2). J Sex Med. 2011 Apr;8(4):1171-6. doi: 10.1111/j.1743-6109.2010.02167.x. Epub 2011 Jan 17. PMID: 21241454.

Waldinger MD. Post orgasmic illness syndrome (POIS). Transl Androl Urol. 2016;5(4):602–606. 10.21037/tau.2016.07.01.