Question about anti-bodies

[itexpat]

Hi all,

I wonder what people know about this : is having a Scl-70 positive always connected to the diffuse form of scleroderma? I seem to be reading contrasting opinions about this and I am interested as I am positive at Scl-70 value 73. Thanks

[Rescue5]

I have diffuse Systemic Sclerosis with positive SCL-70. As you may be aware it is a rare autoimmune disease and can be difficult for one initially to come to terms with.

However what I would say is that your physical symptoms, along with the blood tests are contributory pieces of information that will be used by a specialist rheumatologist to assess your situation.

Therefore talk over such things with your rheumatologist and ask questions. I wish you well.

Kind regards.

[Tiggywoos in reply to Rescue5]

Do you mind me asking please if you have any other positive anti bodies alongside scl -70? X

[itexpat in reply to Tiggywoos]

Of course..I have Anti-RNP (1.90 U/mL) and a low centromere: 0.40

[OldTed60 in reply to itexpat]

Sorry to pick you up on this but which anti RNP antibody do you carry as there are several? One is U1 RNP which is specific to MCTD and the other is U3 RNP specific to Systemic Sclerosis. Also I’ve read experts explaining that SCL-70 can often give false positives.

When I was being repeatedly tested I had weakly positive showings of Th/ To antibody a few times - which is always Limited skin involvement but with a poorer overall prognosis. I was told that they don’t bother about weak antibodies and only trust high positive antibodies that show up repeatedly along with related symptoms

There are about 13 SSc antibodies. I carry a highly positive rare SSc antibody, U3 RNP / Fibrillarin, which is more commonly associated with diffuse than limited. However Prof Denton diagnosed limited for me but said this only relates to my skin involvement. My main risks are severe scleroderma GI involvement which I already have, sudden renal crisis, PAH, cardiomyopathy and Myositis.

[itexpat in reply to OldTed60]

Hello, I do not know about U3 RNP. It is not in the list on my results. However my Scl-70 has showed up on two separate occasions, so I am afraid it might be really positive. My rheumatologist diagnosed limited for me too. Possibly based on my limited skin involvement. I have some GI symptoms but not too severe at the moment. So I do not know what to expect...I would just like to know whether a diffuse involvement is likely or not. During my specialist appointment my rheumatologist diagnosed limited...so I do not know what is more reliable: the anti-body or the clinical examination???? Regards

[OldTed60 in reply to itexpat]

U3 RNP can also be referred to as Fibrillarin antibody on lab results. If a rheumatologist can’t find reasons for a patient’s apparent scleroderma symptoms then there are much rarer antibodies they can look for and this and Th/ To are two such antibodies - both pointing to severe end of limited - which can actually have a worse outlook than diffuse btw - especially if someone carries a diffuse antibody such as mine and the Th/To. I don’t know what it signifies if the SCL-70 false positives repeat but from a different online (mainly American) group expert I think it’s all about your titre/ level and which panel they are showing on. I don’t carry SCL-70 so this isn’t my thing but I’ve read elsewhere that weak positives are often false. Either way I wouldn’t dwell on distinctions between limited and diffuse as they are a red herring.

I showed my own high positive results to the chap on Facebook who advises as a patient expert, Ed. He runs the scleroderma education project and he showed it to an immunologist specialising in lab results. He agreed that this was too high to be ignored, same as my hospital immunology team. But unlike them he said it was almost certain that I have scleroderma rather than just severe Sjogren’s Overlap CTD as previously assumed. It all hinges on your nailfold capillary results in my hospital and at Royal Free. Antibodies only count for so much where it comes to diagnosis. This capillaroscopy is the test that finally clinched my diagnosis at Royal Free two years ago.

The specific antibody we carry is most useful in giving us an idea of future outcomes and risks - whether our symptoms are mostly Scleroderma or Myositis, Sjogren’s or Lupus etc. The diffuse v limited distinction is only marginally useful for clinicians where it comes to rapid disease progression and targeting of preventative treatments. In the long term it’s all Systemic Sclerosis and heart and lungs can be equally affected by both cutaneous subtypes. The milder antibody is usually ACA which is the one used to be known as CREST. I don’t carry this at all but know that it’s associated with less serious disease. However there are always exceptions

[itexpat in reply to OldTed60]

Thank you, OldTed60. this is really informative and precise. I think I do carry ACA, but very low.

[OldTed60 in reply to itexpat]

You’re welcome. Considering I didn’t even take my O’level in biology I think I’ve learnt rather a lot of science over the last 14 years! I guess many of us with rare diseases are forced to become expert patients and also patient activists just to get a proper diagnosis we can trust. My doctors often ask me for advice about my conditions these days which is flattering but also rather alarming!

I have a weakly positive Th/To which sometimes shows alongside my Fibrillarin/ U3 RNP. Prof Denton said it’s quite common for patients to show other weakly positive antibodies from the same ANA pattern/ family but he tends not to pay heed to them as they are likely just false positives. But I thought it was interesting that he diagnosed my scleroderma as limited given the presence of this weak positive. Th/To is specific to limited although has a much poorer prognosis than ACA. I’m guessing that this must be at least partly why we are both diagnosed with limited rather than diffuse - but who knows. I read the first large scale European research study undertaken in my antibody - a French study in 2021. It concluded that, with AFA/ U3RNP the distinction between limited and diffuse is unhelpful. They didn’t find any differences in 5-10 year outlook in mortality or internal involvement - the only distinction was in the amount of skin involvement. I would think Prof Herrick would say same of your limited diagnosis re antibodies. The main thing is to get started on disease modifying treatments as soon as possible. This diagram I found might help clarify a bit.

Colour photo showing diagram of scleroderma antibodies and their associated risks

[itexpat in reply to Rescue5]

Thanks for this. I wish all the best in your treatments. I will talk to my rheumatologist as soon as I can...not very easy to catch,X

[LadyTrundle in reply to itexpat]

Sorry to jump on this thread but the discussion was so detailed it prompted me to actually look at the test results I had from 2023. The only positive ones were CENP A antibodies and CENP AB. I think that means Limited form more than diffuse? Is that what your understanding would be, you clever people?!

[Prettyfalcon]

Hello,

I have a strong positive Scl-70 antibody with a diagnosis of limited systemic sclerosis.

Prof Denton explained to me that the diagnosis is based on skin involvement and the Scl-70 antibody merely indicates a slightly higher propensity to develop issues with the heart, lung and digestive systems, which is why they repeat baseline CT/echocardiograms annually. He also explained that people without the Scl-70 antibody can also go on to develop all of the same issues too, so the label they give you is based on how much skin is affected and where.

Hopefully you have a good consultant who can walk you through all of this and get you on a good condition management plan 😊

[itexpat in reply to Prettyfalcon]

Thank you for this answer. It is useful to know what Prof Denton said about this. My consultant is Prof Herrick, who, I read, is also a specialist in scleroderma. During my appointment she diagnosed limited at an early stage, but did not say much about the possible progression. I will not be able to talk to her soon nowand I just keep onstrassing about this Scl-70....

[OldTed60 in reply to itexpat]

Gosh I thought Professor Herrick had retired from clinical practice and was just focussing on research now? I looked her up as had heard she’d moved back to Scotland where I live. Couldn’t find much but she’s meant to be excellent

[kali9 in reply to OldTed60]

Hi, I hope someone can help me interpret these results. I have copied the part of the results that were highlighted in red by the lab. I am still struggling to understand what all the numbers mean. I have been diagnosed with lupus and also have Raynaud's and livedo reticularis. I feel like something else might be going on and according to the results I also tested positive for mixed connective tissue disease. I am experiencing a lot of digestive issues but I was told lupus does not causes digestive issues. I wonder if in addition to lupus I have Sjorgens or scleroderma. According to the hospital many people have overlapping symptoms so it is possible I have another condition. However they said the medication would be the same.

ENA + DNA (LABUSE ONLY) - (DJT) - Req by FH -

been referred to rheumatology

ENA antibody level

Negative

ENA screen comprises:- RNP70/U1RNP, Sm, Ro52/Ro60,

La, Scl-70, centromere and Jo-1.

We are awaiting UKAS accreditation for this test

! dsDNA binding autoantibody lev 271 iu/mL 0.00 - 27.00iu/mL

! Connective tissue ab. screen

POSITIVE

Screens for antibodies to:-

Ro, La, Sm, RNP, Jo-1, Scl-70, dsDNA, Centromere,

Mi-2, Ku, Th/To, RNA polymerase III, PM-Scl, PCNA,

and Ribosomal P protein.

Immunology general comment

Interim Immunology report; further results

associated with this request to follow.

15-Dec-2022 HEp-2 cell pattern - (DJT) - No action

1/320 dense fine speckled nuclear pattern and

coarse speckled cytoplasmic pattern

15-Dec-2022 ! Connective tissue ab. screen - (Fariha) - positive -

referred to rheum

POSITIVE

Screens for antibodies to:-

Ro, La, Sm, RNP, Jo-1, Scl-70, dsDNA, Centromere,

Mi-2, Ku, Th/To, RNA polymerase III, PM-Scl, PCNA,

and Ribosomal P protein.

[OldTed60 in reply to kali9]

Hi. I think you should post this question on the main group because more people would be able to respond and maybe more knowledgeable about other conditions such as Lupus and UCTD - which I don’t have myself.

However I do know that the more antibodies we carry for different rheumatic diseases, the more likely you are to be diagnosed as UCTD (undifferentiated) rather than seropositive Lupus, RA or Scleroderma as a full blown entity. Sjogren’s is regarded as a little bit different as it often overlaps and can be diagnosed and confirmed by Sicca symptoms and lip biopsy as mine was. I only carry a single Scleroderma antibody at a high titre and this, apparently, is the case for most people with Scleroderma. I think this also applies to the others as well though. You seem to have many positive antibodies rather than just one single antibody. However I’m not medically qualified so I could be wrong - but this is certainly what I’ve been told by experts.

[kali9 in reply to OldTed60]

Hi OldTed60, thank you for your reply. I will post the question in the main group.

[UG2025]

Hi I have read through the comments and wonder if anyone with diagnosis of scl-70 is on immunosuppressive medication.. I have scl-70 with lung involvement but thankfully very stable and limited lung decline.. I didn't like taking mycophenolate immunosuppressive meds because I had repetitive illness and kidney infections as well as ulcers that wouldn't heal... since I stopped taking mycophenolate my ulcers have healed and everything seems stable but my consultant is looking me to go onto myphoric the one below mycophenolate because he is advising i need to be on something for my skin. But I really feel fine and whilst I have one ulcers starting I blame that on missing my flolan this year...

Any comments around immunosuppressive meds would be so appreciative