Saturday, February 17, 2018

CHIP, immune disorders, osteoarthritis, and hydroxychloroquine

A footnote in my post on Kateva’s liver disease linked to a NYT article on CHIP (clonal hematopoiesis of indeterminate potential). Wikipedia calls it “Clonal hematopoiesis”. To put it mildly, this is a hot research topic (wikipedia, lots of 2017 edits) …

Recently, several independent studies have confirmed the presence of malignancy-associated mutations in the blood of individuals who have no clinical signs of hematologic malignancy.[4][5][6] In combination, these studies have demonstrated the widespread incidence of clonal hematopoiesis in the healthy adult population and have stimulated further efforts to broaden our understanding of clonal hematopoiesis in health and disease.

Whenever we discover something new about human biology we round up all the diseases we don’t understand and look for a connection. The main focus now is on CHIP’s role in atherosclerotic heart disease, but I assume all the immune disorders are being CHIP tested. (I couldn’t find any articles on this today, which only makes me more suspicious :-).

If you’re going to look at mysterious CHIP disorders, I’d nominate the weird flavors of osteoarthritis. “Osteoarthritis” is an age related disorder (like CHIP), it’s very diverse, some of it has autoimmune type features — feels kind of CHIPpy. (As of Feb 2018 Google and Pubmed found nothing on “clonal hematopoiesis” osteoarthritis [2]. So you might have read it first here, except we know Google isn’t what it once was. Anyway, I’ve created an RSS feed for “clonal hematopoiesis” osteoarthritis — be interesting to see what that link shows in a few months.)

As long as I’m having fun with medical speculation, I’d like to throw in a mention to one of my favorite medications — hydroxychloroquine (HCQ). HCQ started life as a treatment for malaria, but it’s most commonly used for SLE and RA — autoimmune disorders. More recently it’s being explored as an adjunct to chemotherapy.

HCQ was thought to have something to do with Toll receptors (somewhat hot topic), but research on its oncology use focuses on how it interferes with lysosomal mediated autophagy. Autophagy (self-eating) is important for cells, it’s how they recycle their constituents to make new things. Some cells depend on this more than others. Retinal cells rely on autophagy and it’s probably not a coincidence that HCQ can cause retinal toxicity [1].

Cancer cells rely on autophagy too — they don’t have normal cooperative nutritional inputs. Which is why HCQ is being tested for cancer treatment.

Which brings me back to CHIP.  We think CHIP is a kind of premalignant age related disorder of the stem cells that form blood. We think HCQ might impair replication of disordered cells. We know HCQ works for some autoimmune disorders. We wonder about CHIP and oddball autoimmune disorders …

So it would be fun to see if HCQ inhibits CHIP.

- fn -

[1] Worryingly the process can continue even after the drug is stopped.

[2] Actually they both returned results, but they were nonsensical results. I miss when Google used to actually work. It was funny to get a false positive from PubMed, it’s usually reliable.

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