Well just last week I read about the cholesterol-lowering action. I however cannot recall if that effect took 2-3 months to happen like it does for the anti-inflammation anti-autoimmune effects of the drug. I do know the human microbiome project is uncovering new data on how different populations of normal flora impact a person's metabolism, inflammation and glucose levels. What would be interesting is to screen lupus patients who have yet to be treated with any meds and compare their normal flora populations with those of healthy controls.

Thank you both for your responses, i was worried it was a dumb question!

Amy, that study would be interesting. Lupus gut flora vs controls, then a follow up after 6 months and a year to see if the antimalarials were correcting the disease and the microbiota.

To get statistically significant results I think the lupus cohort would have to be narrowed to those with the mild form of the disease- the group who can gain remission through antimalarials alone. The more severe cases are far too complex with the interaction of so many drugs.

Jessy, great overview. I am at risk of twisting the science to fit my hypothesis here, but it wouldnt be a stretch to suggest that antimalarials altering the ph of cells could also have an effect on the composition of microbiota? It does make patients more susceptible to things like UTIs, it would presumably affect the G.I tract too?

What if the skin was involved alongside the G.I tract? It also has a unique microbiota and would be affected by minocycline (which is indicated for acne) and also PH levels. It interacts with Toll-like Receptors, is a site of inflammation and can trigger lupus flares when the cells are exposed to UV radiation- a mechanism lessened/countered by antimalarials.

So what if mild SLE is triggered at the nexus of the microbiota and the host's toll-like receptors both in the G.I tract and at the skin. Pathological changes to the microbiota cause photosensitivity and initiate autoimmunity when they interact with TLRs.

Then antimalarials would work by rebalancing the microbiota and deactivating TLRs. They could do this by altering PH levels and more directly rebalancing the microbiota. In the G.I tract this also causes a reduction in cholesterol, fasting insulin levels etc for the host which are easier to observe and on the skin it reduces cell susceptibility to UV radiation.

Hi Dr. Preston

Very intriguing question! - and relevant to a novel treatment for SLE and other autoimmune disease that we are currently fighting the FDA to get approved.

My colleagues and I are in fact doing some war-gaming on how a test of your hypotheses might be put together. At stake is US FDA approval for a therapy called TOLOVAX which has proven highly effective in treatment of several diseases characterized by dysregulated innate & antigen-driven immunity.including SLE. Our focus is IBD and COPD Please read on and if you are interested in this effort, let`s talk.

As I`m sure you`re aware, in at least one immunocompromised human model, Hydroxychloroquine attenuates activation of innate immune/inflammatory processes stimulated by interaction of LPS on Toll-Like receptors (Blood. Piconi et al 2011;118(12):3263-72). This interrupts a process by which inflammatory mediators such as IL-6 and TNF-a activate JNK and related enzymes, blocking insulin signaling and heat shock protein production, thereby promoting accumulation of misfolded protein aggregates and exacerbating dysregulated inflammation.

One means of testing your hypothesis is to look for evidence that either some component of gut microflora interacts with tissue implicated in SLE pathogenesis – then selectively inhibit various known signaling checkpoints in either in vitro or animal models.

We feel that Hydroxychloroquine may act as a very powerful adjuvant to TOLOVAX. If this interests you, please leave a phone number where I can contact you. Unfortunately, e-mails left on the ResearchGate message board are deleted – so I need to call to exchange e-mails. You can also call me at the number below – but you`d have to deal with a Hungarian-speaking operator, so it`s easier for me to call you.

For reasons of ongoing IP protection, we have not published our most definitive human clinical results, however a general description of TOLOVAX is included in a textbook used here for training of med students: “Pharmacology and Therapy”. You can access the description as follows:

STEP 1. Open this link:

http://gyogyszertankonyv.med.unideb.hu/jegyzetek.php

STEP 2. Select the link to the book:

“Pharmacology and Therapy”

Prof. Dr. Tósaki Árpád, tanszékvezető, DE GYTK, Gyógyszerhatástani tanszék.

It will open into a PDF containing selected chapters of the book.

STEP 3. Go to page 112. The section describing TOLOVAX and the role of New York Eye and Ear Infirmary in developing this technology is begins with the sentence: "At the time of this writing, specific pharmacotherapies capable of including remission of IBD and other severe inflammatory pathologies are not available to the general public."

Hope to hear from you.

Many Thanks.

Sincerely,

David Haines, Ph.D.

Visiting Research Professor

Arpad Tosaki Laboratory

Faculty of Pharmacy

Health Science Center

University of Debrecen

Nagyerdei krt. 98

4032-Debrecen Hungary

TEL: +36-52-25-5586 (office)

E-mail: [email protected]

It would be interesting to see the impact of giving SLE and healthy controls broad spectrum antibiotics to "sterilize" the gut. Then introduce to the non-drug-treated SLE patients flora from healthy controls while those healthy controls are populated with the flora from SLE patients. . Would the healthy controls get SLE symptoms while the SLE patients go into remission??????

In answer to Amy Dugan and partly to Juliet , SLE patients tend to regularly take wide spectrum antibiotics without any real changes in their Lupus status. A lot of SLE patients suffer from persistent upper respiratory tract infections during the winter months, and often have secondary bacterial infections after initial upper respiratory tract viral infections.

I have been looking for a while to study SLE patients as there is a lot of anecdotal evidence from our clinical colleagues that they have an altered stress response (hence my interest) as well as numerous endocrine problems, including anti estrogen antibodies.

Hope this helps

Jon

I don't think the answer is that simple. As with many lupus treatments, I think it depends on the type of lupus and disease state whether antibiotics will have an effect. There is certainly anecdotal evidence out there that some lupus patients on antibiotics see a reduction of disease symptoms. However, nobody has done well-controlled patient studies with broad spectrum antibiotics or probiotics to test gut microflora alterations in lupus disease. It may be that depleting all bacteria is bad, and antibiotic treatment to reduce more pathogenic varieties, ie SFB, would be a better strategy for treatment. The data in germ-free/antibiotic treated mouse models of lupus disease haven't provided conclusive evidence either.

In response to Juliet, I think antimalarial drugs modulate gut flora differently as evidenced in the recently conducted study in our lab ( to be published soon). However, SLE is a complex issue for now but the use of antimalarial for treatment/management of SLE may still depend on the type of antimalarial bearing in mind that their mechanisms of action vary. It is an interesting research to look into.

Having lupus I think that you r are going to have a tough time. The Russians call it the Red Wolf Disease because it mimics other diseases. So While you think that you are treating that particular disease you are not and you can damage a perfectly good organ. My grandmother died of this disease they did a Live autopsy on her after her death by putting her on fife support and they found that several diagnoses were wrong. There at that time where 2 types and she had both. This is why this disease is so hard to pinpoint. Vitamin C with rosehips in some people can hold it at bay. Do not discount any natural herbs in your quest.

Microbiome research is taking off! check out:

Greeling et al 2018 Science Translational Medicine 10(434) eaan 2306

Yacoub et al. 2018 Immunohbiology 223(6-7):460-465

Zhang et al. 2014 Applied & Environmental Microbiology 80(24):7551-7560