Pilot study: "Identification of anti-citrullinated protein antibodies in ‪CFS‬" plus call for funds

[nandixon]

Struggling a little to understand the implications of that. If the false positive rate is different for healthy controls and autoimmune conditions other than RA, something must account for the difference. What could it be?

I'm not sure. It looks as though the autoimmune diseases that tend to cause false positives with ACPA/anti-CCP antibody testing are in the category of autoimmune connective tissue diseases (as is rheumatoid arthritis). It also looks as though false positives may potentially occur, in at least some testing platforms, in the presence of viral infections. (See, e.g., Anti-cyclic citrullinated peptide antibodies: a comparison of different assays for the diagnosis of rheumatoid arthritis.)

 

[nandixon]

This leads me to wonder . . . . Since I only developed RA symptoms more than 20 years after my ME diagnosis, perhaps I really don't have RA, and my positive anti-ccp test is merely a result of long-term ME. My ME symptoms improved for the first few weeks on the chemo drug, but then returned. Perhaps this means I'd be a good candidate for rituximab. Wouldn't that be wonderful, assuming the drug is eventually approved for ME.

The following study suggests that, at least in active RA, a good response to rituximab may correspond with higher anti-CCP antibody titers. I wonder if Fluge & Mella have checked those levels in their rituximab trials and if there's any correlation with which ME/CFS patients are responding or not?

High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis.

Gardette A, et al. Joint Bone Spine. 2014.

Abstract

OBJECTIVE: Previous studies reported that anti-CCP antibody positivity predicts good response to rituximab (RTX) in rheumatoid arthritis (RA). A quantitative approach to such possibility could be a good way to detect the subset of patients most likely to respond. We investigated whether serum anti-CCP antibody titres could predict response to RTX in RA patients.

METHODS: We retrospectively investigated RA patients who received RTX. The primary criterion was decrease in DAS28>1.2 at 6months (M6). Secondary efficacy criteria included a good response and remission according to EULAR. Predictors of response were investigated by multivariate logistic regression analysis.

RESULTS: We included 114 RA patients (81.6% female, median age 53.5 [IQR 45.7-61.2] years, median disease duration 8.5 [4.0-16.0] years). Anti-CCP antibodies were present in 93 patients (81.6%), with median anti-CCP antibody titres 583 [195-1509] U/mL. In all, 44 patients (38.6%) showed decreased DAS28>1.2 at M6. On univariate analysis, high anti-CCP titres were associated with response rather than non-response to RTX (median 1122 [355-1755] vs. 386 [149-800] U/mL, P=0.0191) at M6. On multivariate regression analysis, with a cut-off of 1000 U/mL, anti-CCP antibody titres≥1000 was associated with a decrease in DAS28>1.2 (OR 5.10 [1.97-13.2], P=0.0002); a EULAR good response (4.26 [1.52-11.95], P=0.0059); and a trend for EULAR remission (2.52 [0.78-8.12], P=0.1207).

CONCLUSION: High anti-CCP antibody titres predict response to RTX in RA. This factor, easily assessed in clinical practice, can help with personalized medicine and selecting the best candidates for RTX treatment.

 

[funkyqueen]

It has no bearing on taking arginine supplements.

Oh, ok, thank you Prof Edwards !



( This made me asked to my-self that question) :

" During inflammation, arginineamino acid residues can be enzymatically converted into citrulline ones in proteins such as vimentin, a process called citrullination. If their shapes are significantly altered, the proteins may be seen as antigens by the immune system, thereby generating an immune response.[3]"
( from Wiki )

 

[nandixon]

For people living in the US, in many states this test is available online, without the need to see a doctor (you just go to an available blood draw facility after ordering). For example, it's offered by DirectLabs under the test name:

Cyclic Citrullinated Peptide (CCP) Antibodies, IgG/IgA, Elisa

Cost is $83, and you can sometimes get that discounted with special offers or coupons.

I just ordered this test myself from DirectLabs after receiving a coupon code ("STAR15") that gives a 15% discount (makes the cost $71). I think I'll do the blood draw early next week and will report back when I have results. (That coupon code expires 12/31/2015 if anyone else would like to use it.)

 

[Jonathan Edwards]

I just ordered this test myself from DirectLabs after receiving a coupon code ("STAR15") that gives a 15% discount (makes the cost $71). I think I'll do the blood draw early next week and will report back when I have results. (That coupon code expires 12/31/2015 if anyone else would like to use it.)

OK, maybe we will not have enough publishable data by Xmas, but I think it would be genuinely interesting to see what results PWME on PR get. If we collected all new results on people who have never had the test before and made sure everyone who has it done new reported back I actually think there would be rather little chance of the data being biased. The population might not be entirely representative of all PWME, whatever that might be, but if the null hypothesis that people on PR have the same ACPA as healthy normals is refuted then it might well be enough to justify and even fund more studies. Jo Cambridge would be interested since she is an expert on ACPA.

 

[Gemini]

Results of pilot study: "Identification of anti-citrullinated protein antibodies in ‪CFS‬"

@Dolphin Thanks for posting both this Univ of Vermont study & on another thread Dr. Ken Friedman's 29 min video about it which I just watched:

https://www.cctv.org/watch-tv/programs/update-immunedysfunctionorg

Video summary: 9 min in Ken indicates lead researcher Dr. David Maughan's wife has ME/CFS, the pilot's $25,000 funding came from a patient organization, the New Jersey ME/CFS Association's Research Program, & the materials/tests are readily available off-the-shelf items making follow-up studies highly feasible.

Background on Univ of Vermont research indicating a connection to Drs. Fluge & Mella is here:

www.immunedysfunction.org/research.html

My questions are (1)is Ron Davis' "End ME/CFS Project Biomarker Discovery: Severely Ill Big Data Study" under its Autoantibody Panel testing for anti-citrullinated protein antibodies, and (2) would Dr. Elizabeth Unger add this antibody test to her ongoing CDC seven-site study?

 

[MeSci]

I never had this, or any other antibody tests conducted.

Nor have I. UK-based.

 

[Isaiah 58:11]

@Jonathan Edwards I have. The first time, fortuitously, was by accident; it was to have been added to a different patient's labs.

07/08/2015: CCP Antibodies IgG/IgA >250 High units 0 - 19 (LabCorp)
09/25/2015: anti-CCP IgG 132 Units (drawn in physician's office, unsure which lab they send to)
10/20/2015: CCP Antibodies IgG/IgA >250 High units 0 - 19 (LabCorp)
11/16/2015: CCP Antibody IgG 260 H ≤16 U/mL (Sonora Quest)
11/16/2015: CCP Antibody IgG 264 H ≤16 U/mL (Sonora Quest) - Yes, same day. The test was run twice for some reason.

All other RA associated labs have been negative; I believe the first of those was run around 2008. I saw a rheumatologist in November and had x-rays taken. It is his opinion that I do not have RA, though I probably will in the future.

My Epstein-Barr IgGs (viral capsid and nuclear antigen) are elevated and I read somewhere that there is an EBV link to anti-CCP. My naturopathic primary care doctor thinks the CCP antibodies are related to my elevated Parvo B-19 IgG antibodies. I see in the thread above that there may also be a link to Lyme disease, which I have had two western blots for: both tests were abnormal but negative.

 

[JaimeS]

The coupon code DEAL16 gives you 10% off of a regular-priced lab right now.

-J

 

[nandixon]

My anti-CCP testing (done December 28) came back negative:

CYCLIC CITRULLINATED PEPTIDE (CCP) AB (IGG)

Result: <16
Reference: Negative <20 (units)

 

[RL_sparky]

I had the anti-CCP testing done on December 18th

CYCLIC CITRULLINATED PEPTIDE (CCP) AB (IGG)
Results: 8
Reference: Negative <20

 

[catly]

I test low positive for anti-CCP antibodies and have a + ANA as well as+ TPO antibodies and confirmed Hashimotos on pathology, I've seen 4 Rheumatologists in the NYCity Metro area in the last 4 years- they all just looked at my fingers and said, no joint swelling -- see ya, although 2 of them did acknowledge that positive anti-CCP is a predictor of RA.

So far, I've no joint symptoms except tendinitis in my fingers and feet. Does anyone know if tendinitis is an indicator of RA? I'm not sure if I should continue to follow-up with a rheumy or not, unessisary medical appointments are just a waiste of my limited energy.

 

[A.B.]

A bit late to the party but my test was negative.

CCP antibodies:
Result: 0.1
Reference <5

This was part of a routine checkup where everything was negative despite me feeling miserable just from traveling in a car and getting to the place. And I was short of breath for the next 24 hours.

The only thing that seemed a bit odd was the electrophoresis.

And my erythrocyte sedimentation rate was 2 mm/h, the same as always.

High albumin + low sed rate = thick blood?

 

[MeSci]

A bit late to the party but my test was negative.

CCP antibodies:
Result: 0.1
Reference <5

This was part of a routine checkup where everything was negative despite me feeling miserable just from traveling in a car and getting to the place. And I was short of breath for the next 24 hours.

The only thing that seemed a bit odd was the electrophoresis.

And my erythrocyte sedimentation rate was 2 mm/h, the same as always.

High albumin + low sed rate = thick blood?

Re high albumin, this is from here

High albumin concentrations in plasma
Elevated concentrations of albumin in plasma are caused by a relative loss of water. This occurs in dehydration, or with prolonged use of a tourniquet. There are no pathological conditions other than dehydration associated with a high albumin concentration. Note however that elevated albumin may indicate artefactual elevation of other analytes such as haemoglobin, lipids and calcium.

 

[roller]

wot.. an anti-citrulline antibody?
does anyone really think, this is all about an anti-citrulline antibody?
who is paying for such crap researches?

they are entirely helpless and clueless...

 

[MeSci]

wot.. an anti-citrulline antibody?
does anyone really think, this is all about an anti-citrulline antibody?
who is paying for such crap researches?

they are entirely helpless and clueless...

Have you read the whole thread so as to understand the reason why this might be useful?

 

[msf]

wot.. an anti-citrulline antibody?
does anyone really think, this is all about an anti-citrulline antibod?

No one said that, so how did you come to the conclusion that that is what they think?