Advice please!

[Investigator1]

Hi all, hope you are all ok and keeping safe. So, I have recently had my blood results and my consultant rang me as booked to tell me all my bloods are spot on, however my ANCA marker last July was 3.8, in January this year it had risen to 5.4, and in April down to 4.8. So I was a bit put back by that because I hadn’t had the results since last July. Is this normal? Am I being silly? I am continuing with Rituximab for another 12 months (that was always the plan) I understand equilibrium for ANCA PR3 in 2-3 and above that positive. However she says you just might be somebody who has PR3 levels slightly above then norm. I am a bit confused. Help please.Nick.

[Grizzly-bear]

I’ve not had this myself but I’ve heard from my consultant and others that some people always have positive ANCA even in remission, so it’ll be about you establishing a normal baseline range for you and what is and isn’t a worrying figure, so perhaps if you are in remission and all other bloods are fine you could take this as your normal range and normal fluctuation.

Do you know what your ANCA was when you weren’t in remission as another marker?

[Investigator1 in reply to Grizzly-bear]

Hi Grizzly, nice to hear from you, how are things in the IOM. Well obviously I don’t know what my ANCA level wax prior to diagnosis but when I was first diagnosed I was off the scale in December 2019 at 177+, then after 4 shots of Cyclophosphamide it was described to me as medically induced remission at 90. Azathioprine did it for a while and got it to as low as 40 then back up to 60 so they started me on Rituximab in November 2020. Since then 38, 16 12, 8.2 then end of July (2022) last year 3.8 . Then as stated 5.4 in January this year and 4.8 in March. One thing to consider is that in June 22 I caught Covid and was given monoclonal antibodies in the form of Sotrovimab, almost like at top up on the Rituximab that I had received in May so possibly have given a bit of a false low. My clinician says most people who get GPA have positive ANCA as a norm and that a lot of people who never have Vasculitis are still ANCA positive. Maybe my medium is round the 4-5 mark and it’s always been that. I am not overly worried but glad to hear you comments. Nick.

[Main1234]

hi Nick, these things throw up curve balls don’t they.

We were told that a lot of people remain ANCA positive and it’s what is normal for you and to look at the trend. Are you feeling ok at the moment?

Having antivirals might have given “ false “ results it did for my OH.

Is your consultant concerned as know you have a good one ?

Hope others can offer more advice.

Best wishes

[Investigator1 in reply to Main1234]

Hi Main1234, really good to hear from you. I feel absolutely brilliant at the moment. I always say Rituximab for me is a game of two halves, the first 3 months after the infusion I have a lot of lethargy and don’t feel brilliant, have to watch my sodium more then second 3 months can conquer the Eiger. My Consultant wasn’t worried at all, I am sure she would have said something if she was, especially as it’s going down again. A Guy I met at the hospital who also has GPA who I have kept in touch with says that when he gets a cold or minor infection his marker goes up because what immune system he has starts kicking in. Strange life Main1234, you’re right, curveball, but I do have my baseball bat ready. Take care and stay safe.

PS. Sorry about the dawn chorus reply, I am running my brother to the airport.

Nick

[Chris-Bromsgrove in reply to Investigator1]

Hi Nick. My ANCA PR3 has never got below the twenties since I've been in remission (ten years now). It fluctuates between about 22 to 26 and the odd one has gone into the low thirties but my consultant has said so long as all the other vital statistics are normal there is nothing to worry about. My ANCA was very stubborn to come down and didn't get below 100 until the sixth infusion of Cyclophosphamide. As a consequence I'll probably never come off Mycophenolate but if that keeps me un remimission then happy days. Chris

[Investigator1 in reply to Chris-Bromsgrove]

Thanks again Chris

[Mooka]

Hi Nick

As long as you feel well I don’t think you should worry. Hopefully this extract from the vasculitis U.K. website will reassure you.

After a diagnosis of ANCA-associated vasculitis has been made, regular blood testing for ANCA is part of routine clinical care. Importantly patients with PR3-ANCA at diagnosis have a higher long term relapse risk (50% relapse at 5 years) compared to those with MPO-ANCA at diagnosis (20-30% relapse risk at 5 years). Typically both PR3-ANCA and MPO-ANCA levels fall during treatment, and most but not all patients become ANCA negative over many months. ANCA testing can be very helpful for some individual patients for predicting the timing of a relapse, with a switch from ANCA negative to ANCA positive or a rise in ANCA level predicting relapse. However, these rules do not consistently apply to all patients, making the interpretation of ANCA results less straightforward. For example a minority of patients suffer relapses when they are ANCA negative, and others relapse without a significant rise in their ANCA level. ANCA tests results are therefore always interpreted along side clinical assessment and other blood test results such as inflammatory markers (CRP, ESR), kidney function and urine measurements for blood and protein.

[Investigator1 in reply to Mooka]

Thanks Mooka, really helpful. Nick

[RichardGPA65yrs]

Hi Nick, before you had Rituximab your B Lymphocytes could mature into Plasma cells and continue to make antibodies ie. ANCA.

Rituximab kills B Lymphocytes but not Plasma cells as they don’t have the CD20 protein.

So your persistent low level of ANCA despite Rituximab is probably from old Plasma cells (made pre-rtx) which survive for a few years.

Vascular and therefore tissue damage is what we need to reduce with GPA and a better marker for that is your CRP level and the symptoms that we know.

Glad you are well at the moment. What is your CRP?

Richard

[Investigator1 in reply to RichardGPA65yrs]

Hi Richard my CRP I do not know my CRP but I do know my Albumin and Creatine levels are bang on the middle, in fact my consultant commented on my bloods as excellent.

[ZiggyDiego]

I’ve been ANCA positive since I was diagnosed in early 2017. Like you I have regular rituximab and my result now hovers between 5 and 10. It was 177+ on and off till I got established on rituximab. I have a hierarchy of flare symptoms - I always let the team know if my nose, joints or peripheral neuropathy is worse, or I get a new symptom. That happens every now and again. I know to go straight to eye clinic if my eyes flare or contact respiratory urgently if my lungs flare. That hasn’t happened since 2020. So I’m fairly relaxed about the minor fluctuations of my ANCA. Hope that helps.

[Investigator1 in reply to ZiggyDiego]

Hi ZiggyDiego, yes of course it helps, quite a lot actually. I would gladly take Rituximab for ever but my Consultant is adamant that it’s for a maximum of 3 years which I guess I need to question.

[EGPAGuy]

I have never tested ANCA positive and am told its an unreliable marker at least for EGPA...dont know it it's the same for other ANCA associated vasculitis.

[Investigator1 in reply to EGPAGuy]

Hi EGPAGuy. Don’t know mate, I could well be but thanks for letting me know.

[Johndeeregreen]

Like others have said, watch your CRP levels. I've been on Retuximab 1.5 years now and my CRP dropped to .1 and .2 for the last year. Recently, I started feeling worse than usual ( what's usual since we usually always feel a little off and up and down), breathing difficulty, persistent dry cough. Got blood work and sure enough CRP was 1.8 then lung CT showed new changes. Hit the prednisone at 10mg and was already scheduled for next Retux. Feeling a good bit better, but like others state, will take a while for infusion to really start working.

I work full-time as a PT and run 3 days a week and hike. It's hard but I refuse to let this disease stop me.