Good news to share!

[SusanSD]

Hi John McDonald,

     You are always stretching our neurons …. and sometimes that hurts! 😉 LOL….. seriously, you made me curious about arginine so I searched and found that they consider it a “peptidyl arginine deiminase type 4 (PAD-4)”.  I read about a that investigated whether anti-PAD-4 antibodies are specific to RA, are associated with disease phenotype or severity, and whether PAD-4 polymorphisms influence the anti-PAD-4 autoantibody response. 

      Their RESULTS are as follows (ok to copy here because it's in PubMed): PAD-4 autoantibodies were found in 36-42% of RA patients, and were very infrequent in controls. Recognition by anti-PAD-4 autoantibodies required the 119 N-terminal amino acids, which encompass the 3 nonsynonymous polymorphisms associated with disease susceptibility. Strikingly, the anti-PAD-4 immune response was associated with the RA susceptibility haplotype of PADI4. Anti-PAD-4 antibodies were associated with more severe joint destruction in RA.

        CONCLUSION: Our findings indicate that anti-PAD-4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti-PAD-4 immune response may be involved in pathways of joint damage in this disease. Polymorphisms in the PADI4 gene influence the immune response to the PAD-4 protein, potentially contributing to disease propagation.

        Hopefully, this means that Maz' anti-CCP # means decreased joint damage.

[Patti D]

Hey Susan & Maz,

If it does mean less potential for joint destruction, then why wouldn't they measure this marker at each rheumy visit? This could be important. I had a very high number 221 well over the 60 marker and my RF was 192. I don't see a doc until October which would be 11 months after I started AP. Maz, you said this is your 7 month anniversary. I thought you were diagnosed in 2006? If this happening in 7 short months, that would be promising. I want to meet with all of the BB friends too to celebrate:roll-laugh:

Has anyone else had these tests repeated (RF & anti-ccp)and did they see this kind of progress on AP??? Tell me it is so, PULEEZE!!!! then I too may crack a beer with John or have some cake:roll-laugh:

Happy days!

Patti

[wendi]

I was looking around the old board and found some interesting stuff about ccp.  There are several people who are sero0neg and have much joint destruction and others with a high ccp who have none??  John, Richie, Susan, anyone?

[John McDonald]

Wendi – Idiopathic disease means the idiots don't know what causes it. Most docs are adamantly opposed to looking for bacteria that don't obey Koch's postulates. Famous examples of these by the way would be the bacteria that causes ulcers (Helicobacter) and the bacteria associated with Lyme but there are plenty more known to microbiology that are mysteriously unknown to medicine. Medicine is nothing if it isn't conservative, especially in the presence of Lawyers who are endlessly creative. So they grope for things that they find in association with the set of symptoms that they call RA (or Fibro, or Scleroderma, or Asthma or MS, or …). In this case they found a high correlation between patients with a rock-hard diagnoses of RA and citrulline antibodies, though they have no idea why these are related, only that they are. Anti-CCP could just as easily have been an asparagus spear growing from your ear. If they saw enough of those in confirmed RA diagnoses then they would leap for joy, and they did.

So no, no idea why anti-CCP and RF factor (another mystery) don't accurately predict joint damage. But they sound good, don't they? And doc gets paid to diagnose (name things) and he likes that. Well I like getting paid too, and I do all sorts of things myself to make that happen. Well, back to work now. Cheers.

john

Edited to add:

I should add that if Maz's aspargus spears started retreating from her ears I would conclude that her risk of joint damage would be lessened, though only through that mysterious association that I spoke of, not because I understand the exact relation between asparagus and joint damage. It just looks better without, doesn't it?

john 

[SusanSD]

Patti,

      I don't have RA so I don't know why they don't test for anti-ccp at each visit. I think I read somewhere that some docs do labwork once a year routinely. Maybe they don't think these lab #s will change much in a short period of time so they don't do them as often?

Wendi,

      The fact that the anti-ccp is found in about 40% of those with RA means to me that they still don't have a good predictive model about who gets what symptoms based on what labwork. So, for the remaining 60% with RA, I bet some of those have severe RA or joint destruction. Saying they found a correlation between anti-ccp and severity of RA and joint damage only applies to those who have the anti-ccp antibodies!

      I continue to be ANA negative even though I think I read that 90% of those with scleroderma are ANA positive. Despite the numbers game and what they mean, we all want to get better and beat back these diseases, reclaim our lives and our identities.

      Personally, I think that the cell-wall deficient bacteria are smarter than most people know, forming biofilms which create weapons that our immune systems cannot defend against, at least not without help. Enter antibiotic therapy. Somehow, AP must be able to attack the bacteria's biofilms slowly but successfully. Case in point, the study abstract below talks about azithromycin intering with the quorum sensing (ability to band together via slimy substrate) of bacteria found in the lungs of mice with cystic fibrosis.

“The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM) has been shown to improve the lung function of CF patients. The present study was conducted in accordance with previous in vitro studies suggesting that the effect of AZM may be the inhibition of alginate production, blockage of quorum sensing (QS), and increased sensitivity to hydrogen peroxide and the complement system. Moreover, we show that AZM may affect the polymerization of P. aeruginosa alginate by the incomplete precipitation of polymerized alginate and high levels of readily dialyzable uronic acids. In addition, we find that mucoid bacteria in the stationary growth phase became sensitive to AZM, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results in the suppression of QS-regulated virulence factors, significantly improves the clearance of P. aeruginosa alginate biofilms, and reduces the severity of the lung pathology compared to that in control mice. We conclude that AZM attenuates the virulence of P. aeruginosa, impairs its ability to form fully polymerized alginate biofilms, and increases its sensitivity to complement and stationary-phase killing, which may explain the clinical efficacy of AZM. ^“

^source:

^{Azithromycin Blocks Quorum Sensing and Alginate Polymer Formation and Increases the Sensitivity to Serum and Stationary-Growth-Phase Killing of Pseudomonas aeruginosa and Attenuates Chronic P. aeruginosa Lung Infection in /? Mice}

Nadine Hoffmann,¹*[/suP] Baoleri Lee,¹ Morten Hentzer,² Thomas Bovbjerg Rasmussen,² Zhijun Song,¹ Helle Krogh Johansen,¹ Michael Givskov,² and Niels H

[wendi]

Thanks John and Susan.  My rf is 571 and acti-ccp is over 100.  I have been like this for 3 years with no joint destruction(yet) and littl pain until starting AP.  Right now I can't reach my hand over my head to wash my hair.  Isn't RA wonderful, so are the idiots that aren't trying to find a cure!:headbang:

[SusanSD]

Wendi,
     I am heartened to hear you have no joint destruction. Is the pain that you're experiencing with the start of AP a herx reaction?
     Here's my beef about the research on the cause for RA and other AI diseases. Just because they can't isolate a bacterium doesn't mean it isn't there. Maybe we don't have the sophisticated technology to “catch” these CWD bacteria. But even if that's the case, if you test the hypothesis and say that these CWD bacteria leave ____ (toxins, signals, … whatever), look for that!
     Hope your lab #s improve soon.

[John McDonald]

I hear the folks were all kind of shocked when the little boy said that the Emperor had no clothes on. The real truth dawned.  In that vein I heard someone say that if the immune system were really attacking self it would do a better job and we would soon be a puddle of enzymes at someone's feet.

 

I suppose we could have that kind of shock if someday with PCR and genomic sequencing and such they could definitively prove that there are no bacteria. But that day they will have to explain this uncanny herxheimer response I have come to know so well.

[John McDonald]

Wendi – how long and how hard are you hitting the antibiotics? Maybe you need to back off a bit.

[wendi]

John,

I started every other day 100mg and did fine for 2 weeks.  Then I did everyday 100mg for 4 days had a heck of a herx and took nothing for 5 days.  I then started 100mg m-w-f and have been doing that for 3.5 weeks now.  I take global minocycline.  Right now I just found out i have a sinus infection too so I was given augmentin.  As I was taking this pill tonight I decided to read the warnings.  It said something about if you are taking tetracyclines you need to be monitored more closely hen taking this ax.  ihave no idea what that means.  I know you're not a doc, but any thoughts?  I called the pharmacist and she was useless.  Just read the same thing I did.  Gee thanks.

 

Wendi

[John McDonald]

How do you know that your sinus infection isn't also a herx? I know people who have started AP/MP for chronic sinusitis and guess what kind of herx they have? That would include my beloved wifey. If you want to explore that angle then lay off all your antibiotics for a few days and see if your sinus infection clears up. If it does then the Minocycline is already doing what it is supposed to and the Augmintin may be in the way.

From rxlist.com Augmentin is a new age descendent of penicillin, many times reformulated to foil the bugs. I didn't see any warnings about tetraclines on rxlist and I don't have time to look elsewhere. I also cannot remember if there were any warnings on the Road Back reading area about mixing bacteriocidals and bacteriostatics but you may want to look.

[Maz]

[user=287]Patti D[/user] wrote:

If it does mean less potential for joint destruction, then why wouldn't they measure this marker at each rheumy visit? This could be important. I had a very high number 221 well over the 60 marker and my RF was 192. I don't see a doc until October which would be 11 months after I started AP. Maz, you said this is your 7 month anniversary. I thought you were diagnosed in 2006? If this happening in 7 short months, that would be promising.

 

Hi Patti,

My LLMD repeats all the tests every month in the early days (depending on severity of patient symptoms) and then every 2 months once improvements begin. As his patients start to feel in better shape, he extends the periods between bloodwork testing. I'm still at the 2 month interval stage, though my visits to him are becoming fewer. Having regular bloodwork done is just his way of keeping tabs on me in between visits. I saw him in early May and he said he didn't need to see me now until late Sept. He didn't tell me at the outset when I first started seeing him, but he later said that I was one of the worst cases of Lyme reactive arthritis he'd ever witnessed. I'm pretty glad he didn't tell me this in the beginning, as I would have felt even more hopeless!

I think he also feels it important to collect data on all his patients simply because Lyme is still so controversial with the mainstream. Having patient data to actually back up his treatments is a safeguard of sorts. Regular rheumies probably don't feel this kind of pressure. Lyme docs also tend to watch closely for dips in progress, as they generally change up the protocol on a regular basis to keep things moving in the right direction. The other side of things is that he's very much into educating other doctors about chronic Lyme, so speaks at a lot of conferences and symposiums…just  having patient data to present and to illustrate the longterm progress that patients experience on antibiotic therapy, without the patient being present for evidence, is a handy tool.

As for rheumies, they probably don't feel the need to check anti-CCP or RF on a routine basis at regular intervals, because they're just not expected to come down to any great degree. They're just diagnostic/prognostic markers, in effect…and, as John remarked, it's not clearly known what significance these antibodies have, anyway, except that they seem to appear in different degrees with different patients (not all)and provide some clues about how aggressively they need to treat.

Overall, the difference probably lies in the huge gap between rheumies who don't believe in infectious causes and LLMDs and AP docs who do?

Maybe this study on Remicade says it all…. 

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=416448

According to this study, RF seemed to come down in a steady pattern by about 50% over a period of 78 weeks. However, anti-CCP only came down in the early part of the study by about 25%, but then leveled out and no further improvements were seen in all but 2 of study subjects. I interpret this to mean that the anti-CCP is just one of those numbers that isn't tested repeatedly thereafter, not only because of its cost, but because it's generally not considered useful after that.

My RF was in the mid-500s at the outset….it's now 35. That's a 500% decrease during the period between Nov. '06 and now, July '08….bascially, 1 year and 8 months or 84 weeks. That's just 6 weeks longer than the study results of remicade, above. I don't know what my anti-CCP number was as the lab only gave a >60 number. However, in only 8 weeks, it came down by approx 35% on AP (assuming it was no higher than 61 in early May at my last test). That's remarkable, considering anti-CCP only came down by 25% in almost all patients during the 78 week study and didn't improve for the larger part of the remainder of the study. 

This is not to brag in any sense….just seems to offer proof positive that AP works and, although it may mean a worsening of bloodmarkers in the beginning due to herxheimer's, the expected longterm trend is for the majority of APers to just continue improving….maybe some hiccups along the way, but nevertheless to experience solid improvement and eventual remission.  

Patti, you're right, I did start with high dose antibiotic combos for borreliosis and “friends” in the first year. It was only in December of '07 that I began low dose AP on minocycline (along with high dose rifampin for two months and then switching to low dose, pulsed zith in March).

Maybe around Thanksgiving or Christmas we should all try to meet up in the Road Back chatroom for some giggles?!!! :roll-laugh:

Peace, Maz

 

[Tiff]

John said:   “In this case they found a high correlation between patients with a rock-hard diagnoses of RA and citrulline antibodies, though they have no idea why these are related, only that they are.”

The correlation route to science is getting to be epidemic.  Did anyone recently read that the drug they have come up with to remove plaque from the brain of patience with Alzheimer's works to remove the plaque but doesn't stop the dementia?  Seems like the same problem to me.  They fail to establish an causal relationship, no real theory of what is going on, so their drug doesn't help.

I suspect that the plaque is only evidence of the body fighting (albeit unsuccessfully) the real cause of the disease (pathogen?), so removing that evidence doesn't do a thing for the real disease!  Theoretically, it could even make it worse as it interfers with the bodies own defenses.

For me, I have just had to remember that these tests and numbers don't tell the whole story and take them with a grain of salt.  But it is nice when they look better!

[Patti D]

Hi Maz,

Wow! I haven't been looking at any anti-ccp stuff on the web for at least 6 months because I freaked out the first time and didn't like to read all of the doom & gloom.It scared the bejeebies out of me and truthfully, I thought I would never be able to do a thing again.

I have concentrated all of my efforts on this board and the “Arthritis Breakthrough” for educational information as well as inspiration, hope, clarity and a lesson in perseverance. Something about positive energy has kept me going on my road to better health. So , last night I spent around 2 hours reading everything I could about anti-ccp, all of the good, bad and ugly:shock: This time, with a more scientific mind:dude:.

Anti-ccp can be elevated in all of the “pea soups” of all “autoimmune” diseases. It is also elevated with some infections(like lyme???), Tuberculosis & Hepatitis C. Some eye infections, gum disease and probably a host of other things i didn't find.Just looking at those 2 diseases, TB & Hep-C one bacterial and the other viral, I can't help thinking that there is only one reason that anti-ccp is also elevated with RA. It also is caused by some creepy bug:sick: , mycoplasma.

There was a pretty good article in the Oxford journals(recent June 2008) on how anti-ccp DOES NOT PREDICT DISEASE PROGRESSION!!! This is the first time i have heard that as just like you I was told and did read in all of the rheumy junk that the presence of anti- ccp was an indication as to severe joint erosion and that rarely do the numbers change.:headbang: This is the kind of contradictory information that really ticks me off and makes me wonder,” who really is watching the store.” It is so saddening to the patient to get such a diagnosis to begin with. Then to have someone tell you, oh yeah yours is the severe aggressive form of RA based on your numbers.:crying:

Reality always creeps back in in subtle ways. A friend of a friend was told she had 6months to live with her 4th stage pancreatic cancer. That was 3 years ago!!! Another friend suffered severe spinal injuries with head injuries and was told he wouldn't live and definitely never walk if he did live. That was last summer. He is still rehabbing but is driving a car, walking with help of a 4 point cane, even though he is still paralyzed. So my point is we really need each other on this board to pump each other up. We need to rejoice in each others accomplishments and spread some courage to those who are suffering.I am thrilled that your numbers are going back to normal because that tells me and gives me hope that next year or sooner:cool: that I will be saying the same.:blush: 

One thing that is really eating at me is the feeling that I should reallly have an LLMD. That's because of Pam Weinthraups book and now your success. I have the name of the one LLMD in Wisconsin, but wonder if I am up for this. What do you think? I am continuing to improve with some peaks & valleys but wonder do I have to start all over with another doctor. I can't imagine taking the amount of antibiotics you did as well as the accompanying herxing. I've got to work girlfriend and really dont's know how I could do that intense treatment. I am doing the 200mg bid now and hoping I eventually can get that down to m-w-f but the minute I” play” with the dosage I Ifeel like crap 2 days later and no doubt it is a herx. I like what John said, kill the microbe not the patient.” Even though I am at the dosage of anti inflammatory usage I am still killing the stinkers. I may just wait for Trudi to let me know how her appointment goes . We have another similarityMaz. I have Blue Cross/Anthem as well so maybe even out of network, some of the bill  of the new LLMD could be covered by insurance. I will look into it. I don't know what to do.

Thanks Maz. You keep me on the right road.:D

Happy days!

Patti

 

[Patti D]

Opps!!!

Yeah, let's have a good cup of Jo in the chatroom:roll-laugh::roll-laugh::roll-laugh:

Chatty Patti:D

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