Help understanding graft-vs-host disease

Factual Questions
1

I was at a blood bank symposium today, and someone mentioned transfusion-associated graft-vs-host disease, which reminded me that I’ve had a question about that in the back of my mind for a long time.

Why is GvH more likely when a unit of blood is coming from a sibling, as opposed to a randomly-selected donor? Given that it’s an immune response by the donor white cells attacking the host’s body as foreign, I’d think that being less foreign (sharing an HLA haplotype) would make it less likely. But from what I’ve been told, it’s the opposite, which is why we always irradiate any directed-donor units that are coming from the patient’s immediate family, so we can inactivate the white cells.

If anyone can help me understand this, I’d really appreciate it. It’s probably really obvious, and I’ll kick myself later, but my brain is stalled.

Bonus question! Why do GvH symptoms involve the skin so much?

2

I’m bumping this because I’m hoping someone smarter than me will see it.

3

Heh, I assumed you would be the person on these boards best able to answer this!

Just a total WAG, but I seem to recall that the skin, being the “first” barrier protecting you from the outside world, has a very high concentration of immune-related cells, and immune responses can come from the skin layers very quickly. Perhaps that might explain the link to skin problems showing up first? If that’s the part of your body with the strongest response, then symptoms would show up there, first.

I assume you already know what’s in this wiki article, or that your general knowledge of the field is more in-depth already? Graft-versus-host disease - Wikipedia

Good luck finding the answers to this!