Treatment of our choice

[Jasper]

Sharon, here is the link to the 120 week study. The article is excellent, but you can see just by looking at the graphs, tables, and figures that there is significant improvement with Rituxan.

http://arthritis-research.biomedcentral.com/articles/10.1186/ar4359


That Rheumatologist who "does not believe in it" is not only an ignorant Rheumatologist, but she is also doing a major disservice to any patients she shes.

[Sharon]

Oh thank you for this Jasper! 
Can you explain what they mean by: "ectopic lymphoid structures and germinal center-like structures"?

[WhatYouSjo]

There are several reasons that stem cell research has moved slowly. First, there is a high cost to such research, and pharmaceutical companies rarely want to invest significant sums of money without being guaranteed a return. In this case, they would want a patent on the specific stem cell therapy, and such patents are still a bit of a new area in law.

That leaves government research grants, but there have been issues there as well. In the United States, President Bush signed an executive order in 2001 blocking funding for large amounts of stem cell research for roughly 8 years. That is one reason countries like China moved to fill the void.

I would add that there is still significant research being conducted worldwide using MSCs as a treatment for a variety of illnesses and injuries. A quick Pubmed search on 'mesenchymal stem cells' returned 26602 publications in just the past 5 years. The researchers who published the 2012 study I linked to previously have been working on many projects, including tooth regeneration (2013), lupus and scleroderma (2015), and even regenerating salivary glands (2015). All of these topics are relevant to SS patients, even if they aren't directly involving SS. Unfortunately, SS is rarely prioritized as a candidate for promising new treatments. We may be lucky to even have the 2012 study. That being said, with the money being poured into stem cell research, I think we can expect SS patients to benefit, even if we are forced to wait in line behind other, more prominent illnesses.

[Sharon]

Thanks for clarifying the matter WhatYouSjo.
I wish those researchers would have published a follow-up to their 2012 study instead of moving on to additional studies.
That gives the impression that they're somewhat "touch-and-go". 
Do you feel it's safe to try the treatment at the current stage it's at?

[gurs]

Dawnmist...

Because there is not one certain test for all autoimmune disease that is conclusive, you might want to see if your doc, or another doc can write the order for Rituxan for RA. Im sure most of us have some of this anyways. Medications can also interfere with blood tests too.
I think its a matter of how the doctor writes it? Does any of your joints hurt at all? I can barely bend my fingers now, but my labs dont indicate I have any RA either?

Hope you can find something to help.

Gursie

[Dawnmist]

Dawnmist...

Because there is not one certain test for all autoimmune disease that is conclusive, you might want to see if your doc, or another doc can write the order for Rituxan for RA. Im sure most of us have some of this anyways. Medications can also interfere with blood tests too.
I think its a matter of how the doctor writes it? Does any of your joints hurt at all? I can barely bend my fingers now, but my labs dont indicate I have any RA either?

Hope you can find something to help.

Gursie

Thank you Gursie.

The only times my joints have hurt have been due to tendinitis (except for one finger joint that got broken in a motorbicycle accident a decade ago). No swelling, no erosions visible on xray, nothing not fully explained by Sjogren's itself. I do get muscular and neuropathic pain, the tendinitis has been controlled for the last 21 months by anti-inflamatories, so no symptoms or evidence that my Rheumy could even *hint* at being caused by RA. Hence why he attempted sending me through the Lupus clinic last year. He has *tried* to work around the system. The only decision I've been annoyed with him about is his recent decision that Cellcept would be too risky to try for too little gain (and for not starting to look at treatment to slow the progression when he first suspected what was happening about 12 months earlier than he actually did). The specialists here seem to be a lot less gung-ho about intervening here than people report in the US. That said, when I first saw him I was starting to have suspicions that some of the pain I was experiencing may have been small fibre neuropathy, and he assured me at the time that in the 30 years he'd been practicing as a Rheumy he'd only ever seen 2 Sjogren's patients that had anything other than "dry eyes, dry mouth", one of them only mildly and the other one more strongly. He was trying to be reassuring. As a result, I *know* that I am presenting him with issues that he doesn't have experience with dealing with. Our population is so spread out in Australia that I'm not sure that there will be many Rheumies at all who *would* have experience with them - not unless they've spent several years working somewhere more populous like London. I know he's been in contact with Julius Birnbaum for advice to try to get me the best help he could. It's just that the advice he was given (use IVIG) is impossible to do in Australia.

General docs are not permitted to prescribe Rituximab here. It has to come from a Rheumy (or I think an Oncologist for certain types of cancer), and they have to get health department approval. Otherwise you as a patient are up for the entire cost yourself, which is just too darn much to pay. With health department approval the cost drops to the equivalent of a $38 co-pay per dose. Without approval, it's somewhere more like $10,000 per dose. He would have done them himself otherwise instead of having to try to send me through the lupus clinic (on the basis that "active" sjogren's is not that dissimilar to active lupus).

[Jasper]

Sharon .....

This explanation is from an good article I found on the topic. The article is oretty detailed but it is well worth the read.

"Ectopic lymphoid-like structures (ELSs). Highly organized lymphoid aggregates that form in tissue sites that are not typically associated with lymphoid neogenesis."

"Ectopic lymphoid-like structures often develop at sites of inflammation where they influence the course of infection, autoimmune disease, cancer and transplant rejection. These lymphoid aggregates range from tight clusters of B cells and T cells to highly organized structures that comprise functional germinal centres. Although the mechanisms governing ectopic lymphoid neogenesis in human pathology remain poorly defined, the presence of ectopic lymphoid-like structures within inflamed tissues has been linked to both protective and deleterious outcomes in patients."

"Germinal centre.  Located in peripheral lymphoid tissues (for example, the spleen or lymph nodes), these are sites in which B cells proliferate and clones that produce antigen-specific antibodies of higher affinity are selected."

ELSs in autoimmunity and the emerging role of Epstein?Barr virus.
"The presence of ELSs with the appearance of fully functional ectopic germinal centres has long been described in the inflamed target organs or tissues of patients who are affected by autoimmune diseases, including the synovial tissue in rheumatoid arthritis, the meninges in multiple sclerosis, the salivary glands in Sj?gren?s syndrome ..... . In these clinical disorders, ELSs develop in response to disease-specific autoantigens, which also ensure the long-term maintenance of these structures within the inflamed tissue.The presence of ELSs in autoimmune conditions perpetuates  autoimmunity  towards  disease-specific antigens. In this respect, many of the regulatory mechanisms that govern tolerance within SLOs are not seen in autoimmune disease-associated ELSs. For example, in SLOs, autoantigen-binding B cells may be excluded from entering germinal centres and they lack responsiveness to CXCL13 owing to a downregulation of CXCR5. However, autoimmune disease-associated ELSs permit the entry of autoreactive B cells. This allows for the differentiation of the B cells into high-affinity autoreactive plasma cells that release disease-specific autoantibodies, such as anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis, and antibodies against the ribonucleoproteins Ro and La (also known as Sj?gren?s syndrome antigens A and B) in Sj?gren?s syndrome ..... "

https://www.roswellpark.edu/sites/default/files/pitzalis_et_al_ectopic_lymphoid_structures.pdf

[Sharon]

Thanks Jasper,
Do you know if these ectopic lymphoid-like structures can be detected by MRI?

[Deb 27]

I honestly don't know what med I would choose to be honest. I think Jasper makes a good point that they look at us and twiddle their thumbs. If the lab tests aren't real high and joints deformed, all is good in their eyes.   I also have RA and am just on plaquenil. It gives me anxiety and depression. I had to cut the dose in half and now my joints hurt. They need medication that stops our immune system from destroying our saliva and other moisture producing glands.

I do like my current rheumy though, I think she is better than most. My first rheumy at Mayo clinic who diagnosed me with RA retired. I went there for a 2nd opinion and saw a young whipper snapper who said this was mostly Fibromyalgia and I needed to go to a class for fibromyalgia. Such an A*******. Again, I guess the 3 other rheumatologists I saw were wrong and two of them had practiced medicine longer than he had been alive. But, he knew better.......Right..........

[Sharon]

I hate it when they throw fibromyalgia in our face....
I had one rheumy actually put in writing that he had "no doubt" that my suffering was actually caused by fibromylagia 
Another diagnosed me with fibromyalgia just based on the fact that I brought a written list of all my symptoms to the appointment
(I just have so many symptoms I can't even recall them all during the few minutes doctors allocate me...)
Then he grabbed the list from me and wouldn't let me look at it! 
Finally I found one who told me that all my symptoms were obviously autoimmune especially with the positive ANA and that fibromyalgia is not diagnosed when someone has AI disease since our illness can account for all the symptoms attributed to fibro.

[WhatYouSjo]

Sharon, MSC procedures generally have few short-term side effects. Research is still ongoing concerning long-term effects, with the primary concerns being cancer and infections (similar to biologic drugs). As far as I've seen, there is not yet enough data to say that any long-term risks exist. From one 2015 review:

In vitro and in vivo studies have demonstrated MSCs? pro- and anti-cancer and pro- and anti-infection effects nevertheless, most clinical trials have reported that MSCs-based therapy appears safe and has not been associated with serve adverse events. Together, due to MSCs? context-dependent potential to produce immune-modulatory factors they seem to be an ideal therapeutic tool for both cancer and infections.

There is a commenter on one of my blog posts who has reported receiving the therapy and believes there has been some improvement.

[Jasper]

Sharon ..... i am not sure if  ectopic lymphoid-like structures can be detected by MRI, but they are easily seen when a pathologist examines salivary gland biopsies.

[Sharon]

WhatYouSjo- Thanks for the clarification. I do recall that comment on your blog and hope that
commenter continues to update on his progress!

Jasper- Thanks, that's what I thought.