Is the early Sjogrens test called "Sjo" legit?

[Betsy]

On my paperwork it's called "Early Sjogren's Prof" I assume short for profile. It doesn't say "Sho" but it went to the Buffalo lab Immuno or whatever it was called that's associated with Sjo. My results have been in for days but I won't get them for many more days due to the MD not being there. Lame. I was anxious to get them because the standard tests are always negative for the past decade and I have all the symptoms though I am certainly not anxious to test positive. The thing is though, I worry the test results may not even be valid if it shows positive because I know someone who had the test, they just forced it on her she didn't care for it, and the tested positive. Yet her sole symptom is dry eyes, I am dry head to toe. So I worry it is too sensitive, it detected her dry eyes and diagnoses her with Sjorens. I did a search on here for just "sjo" but of course everything Sjogrens came up lol. Any opinions would be very appreciated, thank you.

[Tharrell]

Hi Betsy and welcome. Yes the test is legit. It's purpose is to catch sjogren's early so that's why your friend may have tested positive with dry eyes beeing her only symptoms. It didn't "catch" her dry eye symptoms, but her positive blood markers for ss-a and/or ss-b. Some here tested positive on this test. I personally tested negative on it. Hopefully somebody will come along who knows how to post the links to the previous articles. Try putting in early sjo test and see if that won't narrow things down.

[Betsy]

thanks Tharrell. Up above I wrote "Sho" when I meant "Sjo"

That's quite a big difference that the traditional tests can't catch Sjogrens even after a decade for someone dry from head to toe, and yet this test can catch Sjogrens with dry eyes only. If it's truly accurate there is no point in doing the traditional tests because their negative so often (even a decade later I can't get over that!)

Thank you  for the welcome

[Jasper]

Betsy .....

I have not had the Sjo test that you are asking about so I cannot comment on it.

I did want to mention that about 40% of people who have Sjogren's Disease are sero-negative. They do not have the antibodies for Sjogren's, but they still have Sjogren's Disease.

Have you had a lip biopsy done? The lip biopsy is considered the gold standard for diagnosing Sjogren's Disease. If you have not had a lip biopsy, it may be worth considering getting one done. One caveat is that the biopsy must be done by a doctor knowledgeable and experienced in doing them and it must be sent to a lab and that has a pathologist who is knowledgeable and experienced in reading the biopsy. If it is not done correctly or the pathologist is inexperienced in reading them, the results can be false negative or otherwise useless.

[WhatYouSjo]

Hi Betsy,

The 'Sjo' test is a blood test that runs the normal, accepted battery of SS tests (SS-A, SS-B, RF, ANA) along with 3 antibodies that are unique to this test. This test was based on studies from the SUNY School of medicine in Buffalo (first study) (follow-up study). From the abstract:

Sjogren's syndrome (SS) is defined by autoantibodies to Ro and La. The current studies identified additional autoantibodies in SS to salivary gland protein 1 (SP-1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP). These autoantibodies were present in two animal models for SS and occurred earlier in the course of the disease than antibodies to Ro or La. Patients with SS also produced antibodies to SP-1, CA6 and PSP. These antibodies were found in 45% of patients meeting the criteria for SS who lacked antibodies to Ro or La. Furthermore, in patients with idiopathic xerostomia and xerophthalmia for less than 2 years, 76% had antibodies to SP-1 and/or CA6 while only 31% had antibodies to Ro or La. Antibodies to SP-1, CA6 and PSP may be useful markers for identifying patients with SS at early stages of the disease or those that lack antibodies to either Ro or La.

To summarize, approximately 30-40% of SS patients are seronegative; that is to say, they test negative for the current antibodies (SS-A/Ro and SS-B/La). The researchers found that approximately 45% of these seronegative SS patients had at least one of the 3 novel antibodies that the group studied.

A company named Nicox decided to patent the markers and produce a test around them (since sold to Bausch & Lomb). The new biomarkers are not recognized as part of standard SS diagnostic criteria, which are decided on by a consensus of medical bodies. As far as I am aware, no one has replicated their studies. That does not mean the results are not valid, but many rheumatologists are unaware of them or will not completely trust them.

One of the key values of the test is that it can be carried out in an optometrist's office, which means that some people with SS will be caught earlier. Because it also runs the usual tests that a rheumatologist would run, it is at least as good as what you would get from the traditional testing route. As a result, it is worth taking if you haven't been previously tested. I personally have tested negative for all antibodies, including the 3 novel ones in the Sjo test, but there are users who report testing positive for the novel antibodies even though they tested negative for the usual ones (SS-A/SS-B).

[Betsy]

Thanks Jasper.


"I did want to mention that about 40% of people who have Sjogren's Disease are sero-negative. They do not have the antibodies for Sjogren's, but they still have Sjogren's Disease."

But how do we know this? Is there anything else that can cause dryness from head to toe? These 40%, did they later in life test positive, is that how we even know they always had it? If so, how many years? One would think a decade was enough....

I had the lip biopsy at the start of my misery but my symptoms were and are extreme, then as well, it didn't start mild and gradual almost a decade ago. It was negative.

[Betsy]

Thanks what your Sjo, I didn't know the names of the specific antibodies before which is useful to know what are the actual markers.

[Jasper]

Betsy .....

Many people who are in the 40% of sero-negative people with Sjogren's do have positive lip biopsies. The lip biopsy confirms the Sjogren's diagnosis in many sero-negative people with Sjogren's.

Many people with negative blood work have Primary Immune Deficiency or Common Variable Immunodeficiencyso they will never be positive to the antibodies for Sjogren's. Their bodies cannot make the antibodies to Sjogren's. There are several people on this forum who have this diagnosis (immune deficiency) along with their diagnoses for Sjogren's.

There are also people on this forum who have neither positive blood work nor positive lip biopsy but their doctors still feel they have Sjogren's

Another thing that will cause a person to have a antibody negative result may be the type of test done. The newer blood test, which is often used, is not as sensitive to the antibodies as the older blood test. Thus, the new test will show a negative result whereas  the old test may have shown a positive result. Both tests are still in use. However,  the newer (less sensitive) test is the one most commonly used now. There are some articles about this but I will have to search to find them.

When I was tested in 2012 by my dermatology PA, she ordered the newer blood test and it was negative. I was told that I had no autoimmune problems. However, I had a lot of symptoms and I felt that I had did have an autoimmune disease. So, in 2013 I went to a Rheumatologist myself. My (new) Rheumatologist ordered a truck load of tests, including the older  more sensitive test for Sjogren's antibodies, and that test was positive for SS-A.

I might add that I have had Sjogren's for decades. However, it was never diagnosed until I saw my fabulous Rheumatologist in 2013. I had systemic vasculitis in 1993-94 and my Rheumatologist at that time did suspect an autoimmune disease. He could not pinpoint the actual autoimmune disease (Sjogren's) because  the Sjogren's testing was very new and not very good at that time. So, I was treated for the systemic vasculitis with high dose steroids. Had the steroids not worked, he would have treated me with Cytoxin. Luckily the steroids worked. The point is, that it was Sjogren's that caused the systemic vasculitis even though I did not get diagnosed with Sjogren's until 2013. 

There are other conditions that can cause dryness but I am not sure how many cause dryness from head to toe.

The important things are  to try to get an accurate diagnosis and get appropriate care for your symptoms. If that means finding new doctors, then that may be the way to go.

[Betsy]

Thanks Jasper. Its a lot of good info though it can be overwhelming because I don't fully understand it all. I have been tested so many times, some may have been new some old of the same test. And now more recently the Sjo which I have to wait for so long. Why cant another doctor in the clinic give me the result, I don't understand making a patient wait.

There is nothing to help the dryness, and topicals are a joke when you are really bad, like my mouth and eyes which are so bad, none of that junk works. It sometimes even hurts us, the ingredients they put in the drops, even the PF ones. So if there is no systemic medicine to get my juices flowing then I don't understand the purpose of knowing ? Other than knowing that later the organs will be involved so one can start stressing early  The rheumatologist even said that systemic meds won't help the extreme dryness. My eyes are out of control. Which is why we began the petition but it doesn't look like it's getting much love here as it did on the dry eye forums. When it goes from extreme dry eyes to corneal neuralgia it's H#@@ pain, 24/7, so for me it's urgent to get closer to the pipeline drops. Its a pain only the most severe patients can truly understand which should be a lot of people here since Sjogrens caused dry eyes is considered one of the worst out there along with Lasik caused dryness and gvhd.

So yeah, I guess I don't understand what you mean by "treatment' if things like Plaquenil don't help the dryness? Not to mention it wont touch cornean neuralgia caused by long term dryness. Is there something new I don't know about? I noticed you had rituxin but hen I begged for it in 2006 they wouldn't give it to me.

I really wish there was an edit option on this forum.

[WhatYouSjo]

One other point that I would add to Jasper's is that Sjogren's has at least two distinct interferon pathways. This was published earlier this year in LEAP, a journal by the John Hopkin's Division of Rheumatology. This means that what we consider SS is actually at least two distinct diseases, which are likely diagnosed differently and react differently to medications. Unfortunately, there is currently no commercially available test to determine which pathway your disease follows and which medications might be effective.

In terms of effective treatment; there are no FDA treatments available today that treat SS systematically. Off-label Plaquenil tends to help fatigue and aches more than dryness. Some people will take stronger treatments like Rituxan or Methotrexate, but there is no solid evidence that they help dryness either, and they can have serious side effects. Many of us have found some success with alternative treatments and supplements such as Ubiquinol and low-dose Naltrexone; the research is often light, but we SS patients have to take what is available. As a number of patients on this forum have found at least some success with Ubiquinol and it is cheap and easily available, you may want to start there.

There are some promising clinical trials in the pipeline. Furthest along is Abatacept (Orencia), a biologic drug scheduled to finish its final stage 3 trial next year. A recent smaller trial for Abatacept on patients with RA and SS found significant improvements in symptoms, including tear and saliva volume, with a third of subjects achieving SDAI remission. While I haven't seen anyone on this forum using it, it is available off-label if you can get a prescription. There have also been promising research around small-molecule inhibitors and stem-cells. So there are reasons to be hopeful.

[Jasper]

Betsy ..... there is an edit button. Just look at the thread and at your post. You will see a "modify" button at the top right side of your post. If you click on "Modify" it will take you to your post and you can correct any errors or add something. After your have corrected or added what you want, then go to the bottom right and "save" your changes.

You can get drugs like Restasis for your dry eyes if an Opthamologist will order them for you. Optometrists can also order Restasis. I had a prescription for Restasis for my severely dry eyes from my Optometrist 2.5 years before I was diagnosed with Sjogren's Disease. I found OTC eye drops to be of zero help. My cornea were getting abrasions and they hurt all of the time. So, my Optometrist ordered the Restasis. That fixed my eyes. He also recommended Omega 3s, which I do take.

I also take CoQ10 and I do think it helps with the saliva. I know my saliva has increased considerably since July 2013. Now, to be forthcoming, I have added several supplements and a couple of meds since 2013 so I cannot be sure what is doing what. I went back on hormone replacement therapy in 2013. I started Plaquenil in 2013. I added CoQ10 and N-Acetyl-L-Cysteine tabs. N-Acetyl-L-Cysteine increases mucous membrane secretion so it may help some with dryness. CoQ10 was shown in a study to increase saliva in about 65% of people. So, I am not sure what is increasing my saliva, but it is increased. I no longer need to carry water with me and I can now eat a sandwich without drinking anything. I don't drink water anymore at night and I don't wake up with a dry mouth anymore. Those are huge improvements.

My saliva has increased even more since being on Rituxan (first infusion Feb. 25, 2016).

As far as treatment with something like Rituxan, you need a diagnosis first. I don't think any doctor will treat your symptoms with Rituxan or any other biologic without a diagnosis first. Insurance companies require a diagnosis or they won't cover it. Also, these drugs are not without risk so a doctor is not going to prescribe them without having a diagnosis first and without thinking the drugs will benefit the person.

As far as the studies on Rituxan go, I really do not understand why the conclusions keep saying that Rituxan does not help people with Sjogren's. The studies clearly show that Rituxan benefits people with Sjogren's Disease. I do know that some of the studies are poorly designed so that they include the wrong people or they have the wrong endpoints or the wrong time frame. If the study does not have appropriate endpoints and the endpoints are not met, then the study is considered a failure even if the people have improved symptoms.

Here are 4 studies and their results. You can see that every one of them shows that Rituxan benefits people with Sjogren's.

1) The first concluded that Rituxan did not help at week 24. But, look at the study. It helped at week 6 and 16, just not at week 24, the endpoint time.
" Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24. Results: No significant difference between groups in the primary end point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P < 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P < 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Limitation: Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes. Conclusion: Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points."
So, the Rituxan did improve VAS but it wore off before week 24. To me, that does not mean it did not work. It means it wore off before week 24. Maybe we need infusions every 20 weeks instead of every 24 weeks. In addition, I will take 4.5 good months and 1.5 not as good months as opposed to 6 bad months.

https://www.scopus.com/record/display.uri?eid=2-s2.0-84894243056&origin=inward&txGid=0

I will add the other 3 Rituxan studies in another post.

[Betsy]

thanks Whats your sjo and Jasper,

Jasper I glad restasis worked for you but for most it does not. Some people it even makes them worse. It worked in only 15% of clinical trial patients so I think you are in the minority and I am glad for you. Most drugs don't move forward at such a low success rate but Allergan calls the shots, their huge. I took Restasis for years without results :/ I have been at this for 10 years (I was a member before but stopped posting as I didn't see anything new coming out to discuss) and tried more than most people, but nothing big like the rituxin.

I already take cq10, nac, fish oil, ldn and more etc...I carry water everywhere and will panic if I forget it. I wake up to drink all night due to the desert in my mouth.

I want to know more about rituxin as well as if it helped your eyes, I will be back later as I am on my way out now, thank you all!

P.S. Sorry didn't realize the modify was edit, my bad, thank u.
I have to be some where soon.

[Jasper]

Here are links to the other 3 studies on Rituxan:

2) This study concluded that Rituxan is safe and effective for Sjogren's:
You can read the abstract but also can connect to the entire article/study.
"In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms).
Conclusion: These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS."

http://onlinelibrary.wiley.com/doi/10.1002/art.27314/abstract

3)  This 120 week study conclude Rituxan is effect for Sjogren's:
"Clinical assessment was performed by ESSDAI every 12 weeks up to week 120 and by self-reported global disease activity pain, sicca symptoms and fatigue on visual analogic scales, unstimulated saliva flow and Schirmer?s I test at week 12, 24, 48, 72, 96, and 120. Laboratory assessment was performed every 12 weeks to week 120. Two labial minor salivary gland (MSG) biopsies were obtained from all patients at the time of inclusion in the study and at week 120.
Results
Our study demonstrated that RTX treatment results in a faster and more pronounced decrease of ESSDAI and other clinical parameters compared to DMARDs treatment. We also observed that RTX is able to reduce glandular infiltrate, interfere with B/T compartmentalization and consequently with the formation of ectopic lymphoid structures and germinal center-like structures in pSS-MSGs.
Conclusions
To our knowledge, this is the first study performed in a large cohort of early active pSS patients for a period of 120 weeks. We showed that RTX is a safe and effective agent to be employed in pSS patients with systemic, extra-glandular involvement. Furthermore, our data on pSS-MSGs provide additional biological basis to employ RTX in this disease."

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

4) You can read the abstract or go to the full article:
"Patients were evaluated, using immunologic, salivary/lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion.
Results
Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. .....Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1.
Conclusion
Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS."

http://onlinelibrary.wiley.com/doi/10.1002/art.21260/abstract

There is also a study on Rituxan and neuropathy but I have to look for that link. It shows improvement in the majority of patients, I think 11 of 17 patients with neuropathy.

[Jasper]

"I want to know more about rituxin as well as if it helped your eyes,"
----------------------------------------------------------------------------------------------

I don't think Rituxan helped my eyes, at least not that I can tell. If I forget to put in the Restasis drops, I will know in a few hours because my eyes start to feel gritty, like sand or a lash in them. So, I don't think it help the eyes, but a real objective test may say differently.

I do think Rituxan helped my saliva flow. My mouth is definitely less dry.

My biggest problem was fatigue. Rituxan helped the fatigue immensely. I went from dragging around forcing myself to do anything (due to the fatigue) and having to rest several times while doing dishes, to being able to accomplish all sorts of things in a day and finish activitiess without resting. I am not back to pre-systemic vasculitis energy, but I feel better than I have felt in about 8 years. I can do things now. I can run several errands at a time. I can plan and actually have the energy to do the things I plan. I can clean and sort and walk and shop. I feel good and I have energy. Rituxan is a miracle for me.

In addition, Rituxan has decreased the peripheral neuropathy pain considerably, 50% for the burning pain, 70-90 % for the electric shocks, crawling sensations, vibrating sensations, etc.

My joint pain is decreased. Urinary symptoms are decreased.

Even my skin seems less dry. My skin is definitely improved from 2013 when it used to flake all over the place even with lotion. Now it is dry, but not flaking. It is improved but I am not sure that is from Rituxan or maybe something else like Omega 3.

Also, I have not had a flare since being on Rituxan. I had 5 flares last year (2015) and was on steroid tapers for all of them. Since Rituxan I have had no flares.

The Rituxan started to ware off about 5 weeks ago. I noticed I did not have as much energy as I did 2-3 months ago. I also had a week of swollen feet, ankles, lower legs (early warning of a flare coming on) but I did not go into a full blown flare. I still felt better than I felt pre-Rituxan infusion, but I could tell it was starting to lose some of its effect.

So, on Aug. 11th  I had the first of my second set of infusions (second infusion will be Aug. 26th). I will keep getting 2 infusions, 2 weeks apart, every 24 weeks. The 120 week study showed even more improvement with the second set of infusions, so I am hopeful. However, I am happy with the great improvement I got from the first set and I will be satisfied with that.

Rituxan has given me back my life and I am very thankful that I have a Rheumatologist who ordered it for me.

[WhatYouSjo]

Rituxan has been hit or miss in studies. The largest study of Rituxan and Primary Sjogren's Syndrome (TRACTISS) (133 patients) found no significant improvements except for salivary flow, but as Jasper pointed out, smaller studies have found it to be more successful. Personally, I think this has to do with the alternate interferon pathways of SS; likely one pathway is helped by Rituxan and one isn't. That would help explain the disparity in studies. There have been enough anecdotal cases of improvement that my rheumatology practice will use it for serious SS cases, though my rheumatologist told me that it typically doesn't help as much with dryness in his experience. There is actually an active phase 2 trial for dual treatment with Benlysta and Rituxan.

Like Jasper said, it seems unlikely that you would be prescribed a heavy-hitting biologic drug without a diagnosis; the side effects can be very serious, including death in rare cases. Orencia/Abatacept is the most promising biologic that I've seen studies for so far, particularly concerning dryness. It is, however, definitely off-label and probably wouldn't be covered by insurance even if you were able to get a prescription.