Log: MCAS with Primary Immunodeficiency

[Gingergrrl]

@ClaireKnowles Is it possible for you to put my words in quote boxes (in your replies above) to make it easier for people to read who are following this thread? I am able to follow it, since I know what I wrote vs. what you wrote in your replies, but I am afraid it might be confusing for others to read.

I think @Learner1 could explain the quote boxes better to you than me but I will try ... if you look at the tool bar there is an icon that sort of looks like an American flag (about 7th from the right side) and if you click on it there is a drop down menu and the first thing says "Quote. If you go back and edit your reply, you can highlight what you want to quote, and then you can put it inside of a quote box.

For new posts (vs. editing one that you have already written), you can highlight the sentence or paragraph that you want to reply to and then click "reply" which brings it into the reply box below. There is also multi-quote (which is the easiest way once you understand how to use it) but I will spare you that part! I'm only mentioning this so it will make it easier for others who might be following this thread in the future.

and @Blake2e I will reply to what you wrote later today (which was very helpful). This entire thread has been very helpful and informative to read!

 

[Learner1]

@ClaireKnowles you can use the quote button as Gingergrrl describes, or another way is to put the word Quote inside square brackets [ ] then add the quoted text, then end the quote with /Quote inside another set of square brackets.

I hope this makes sense.

If not, try selecting some text in a message with your mouse, then click on Multiquote at the bottom of the message, then go to a Reply box and click on Insert Quotes. You'll see the quote with the quote coding inside the square brackets as I described above.

Best wishes,

Learner1

 

[Gingergrrl]

Hi @Gingergrrl! When I said "booster", I meant the maintenance doses after the initial two doses.

Hi CK, thanks for clarifying your protocol and it seems like there are so many terms that are used in different ways! My doctor (our doc) planned for me to have a series of six Ritux infusions over one year (and of course if I was not a responder, that would have been the end of it). But since I had such a significant response, we are now doing maintenance infusions (with my first one on 12/3). But he never used the term "booster" and the original series of six infusions were not part of the maintenance ones (I hope that all makes sense)!

Rituxan has made my joints ache and I've been a bit headachey, but nothing like IgG.

I agree that Ritux is a million times easier tolerate than IVIG (although I never had the reaction to IVIG that you did and am sorry to hear about this).

It would be great if we could get Ocrevus, but I'm sure that is light years away from insurance approval except for PPMS.

How does Ocrevus differ from Ritux? I Googled it and it looks like it also depletes B-cells (CD20)?

Rituxan would kill off the memory B cells but not the plasma cells, which will continue to pump out antibodies for potentially long periods of time.

Thx for clarifying and I wish I could solidly retain all of this info in my brain! Do you know if high dose IVIG touches the autoantibodies that are pumped out by the plasma B cells?

So plasmaphersis and immunoadsorption do the same thing but involve different techniques and they both arent really done in the US? If so than that sucks and thats one back up plan down.

Basically yes. Plasmapheresis (PP or sometimes also known as "PLEX") removes the plasma and replaces it with donor plasma or albumin. Whereas Immunoadsorption (IA) cleans the plasma and then returns it to the body. And PP is more common in the US and IA more common in Europe/Asia. But in general, it is just not commonly done in the US. But I would not give up hope and it is not impossible to get it done in the US.

I still need to ask him specifically why not on my next appt.

I would definitely ask and am curious as to the answer. Where in the US are you located (only if you are comfortable saying of course)!

Rituxan does target some B cells in the marrow but doesnt deplete it there but does deplete it in the peripheral blood. Whereas anti-CD19 would offer both central and peripheral B cell depletion. CD19 and CD20 are different proteins found on the membranes of B cells.

Thank you and I am going to try to remember this. So CD19 and CD20 are two different surface proteins (and not different stages in the life cycle of the same protein)?

I really hope I'm just wasting my time researching this stuff and Rituxan/IVIG does work for me.

As weird as this will sound, I also hope that you are wasting your time and that you will achieve remission from IVIG and Ritux like I did and will not need any of these other meds!

I think thats correct. Good to know about the Quest vs labcorp. Going to have to go with Quest.

I think in general they are both equal but Quest was definitely able to send autoantibody tests to Mayo Clinic and now I have learned that my doctor prefers them for the Lymphocyte Subset Panel.

 

[Blake2e]

Thx for clarifying and I wish I could solidly retain all of this info in my brain! Do you know if high dose IVIG touches the autoantibodies that are pumped out by the plasma B cells?

All of your antibodies are made by plasma cells. IVIG down-regulates (auto)antibody production (https://link.springer.com/article/10.1007/s00415-008-3002-0). IVIG also increases rate of antibody/autoantibody clearance (https://www.ncbi.nlm.nih.gov/pubmed/17101504, http://www.bloodjournal.org/content/bloodjournal/98/10/3136.full.pdf?sso-checked=true).

I would definitely ask and am curious as to the answer. Where in the US are you located (only if you are comfortable saying of course)!

Currently, located in the southwest. Dont want to say which state specifically in public.

Thank you and I am going to try to remember this. So CD19 and CD20 are two different surface proteins (and not different stages in the life cycle of the same protein)?

They are 2 different surface proteins found on B cells. CD19 appears in early pro-B cell and stays till the end of its differentiation process, and CD20 appears on the same B cells but at a later stage in growth.

 

[Gingergrrl]

All of your antibodies are made by plasma cells. IVIG down-regulates (auto)antibody production (https://link.springer.com/article/10.1007/s00415-008-3002-0). IVIG also increases rate of antibody/autoantibody clearance (https://www.ncbi.nlm.nih.gov/pubmed/17101504, http://www.bloodjournal.org/content/bloodjournal/98/10/3136.full.pdf?sso-checked=true).

Thank you for the articles and I bookmarked this post so I can read them in the future. High dose IVIG (the exact mechanism) seems to remain a bit of a mystery in autoimmunity. But as long as it worked for me, I don't need to understand exactly how!

Currently, located in the southwest. Dont want to say which state specifically in public.

No worries and I was asking b/c I was curious if you were anywhere near my doctor (since your doctor might not be willing or able to prescribe a higher dose of IVIG).

They are 2 different surface proteins found on B cells. CD19 appears in early pro-B cell and stays till the end of its differentiation process, and CD20 appears on the same B cells but at a later stage in growth.

Thanks for clarifying that they are two different surface proteins. I guess it makes sense that the Lymphocyte Subset Panel measures CD19 since that appears in the early stages of B cell growth and also stays through the end of the differentiation process. Versus if it only measured CD20, it would not catch the B cells as they are first starting to grow back (after Rituximab). I hope I am understanding this correctly!

 

[Blake2e]

Thank you for the articles and I bookmarked this post so I can read them in the future. High dose IVIG (the exact mechanism) seems to remain a bit of a mystery in autoimmunity. But as long as it worked for me, I don't need to understand exactly how!

The mechanisms of action are debated, but I agree if it works then thats all that really matters.

No worries and I was asking b/c I was curious if you were anywhere near my doctor (since your doctor might not be willing or able to prescribe a higher dose of IVIG).

Thanks but in my condition I wouldnt be able to travel.

Thanks for clarifying that they are two different surface proteins. I guess it makes sense that the Lymphocyte Subset Panel measures CD19 since that appears in the early stages of B cell growth and also stays through the end of the differentiation process. Versus if it only measured CD20, it would not catch the B cells as they are first starting to grow back (after Rituximab). I hope I am understanding this correctly!

I just looked it up and the lymphocyte subset panel doesnt test for CD20, but uses CD19 as a proxy b/c Rituxan depletes that too. Since the test checks B cells in the peripheral blood then low counts of CD19 would indicate low counts of CD20 (since theyre both found on all B cells in the periphery) and that Rituxan is doing what it is suppose to. (source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367089/) Let me know if its still unclear.

 

[Blake2e]

Update: 18 days after finishing Rituxan induction. Seems things are slowly changing. Probably evident by some brain function returning and the ability to do slightly better research and understand a little more of what I'm reading. I'd rate my brain function to be at 0-30% of normal function throughout day, good improvement over being at 0-10% consistently. UV and EMF sensitivity slowly lessening. Still getting adrenalized but lesser symptoms like feeling cold, painful heartburn and body fatigue are coming back as the amount of histamine being released is decreasing. Slowly incorporating some veggies and fats into diet, reactions to food are more milder but still very present. Still want a lot more improvement, I want to completely crush all the reactions.

Still on and rotating high dose corticosteroids. If positive changes persist will start round of Augmentin to clear gut infections and start tapering steroids.

 

[Gingergrrl]

The mechanisms of action are debated, but I agree if it works then thats all that really matters.

I agree.

Thanks but in my condition I wouldnt be able to travel.

I figured it was a long shot!

I just looked it up and the lymphocyte subset panel doesnt test for CD20, but uses CD19 as a proxy b/c Rituxan depletes that too. Since the test checks B cells in the peripheral blood then low counts of CD19 would indicate low counts of CD20 (since theyre both found on all B cells in the periphery) and that Rituxan is doing what it is suppose to. (source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367089/) Let me know if its still unclear.

This completely makes sense that they use CD19 as a proxy for CD20 and if the first is zero (or very low) in the peripheral blood, than it means the second would be as well.

Update: 18 days after finishing Rituxan induction. Seems things are slowly changing. Probably evident by some brain function returning and the ability to do slightly better research and understand a little more of what I'm reading. I'd rate my brain function to be at 0-30% of normal function throughout day, good improvement over being at 0-10% consistently.

This is great news!

UV and EMF sensitivity slowly lessening. Still getting adrenalized but lesser symptoms like feeling cold, painful heartburn and body fatigue are coming back as the amount of histamine being released is decreasing. Slowly incorporating some veggies and fats into diet, reactions to food are more milder but still very present.

Also good news.

Still want a lot more improvement, I want to completely crush all the reactions.

Absolutely and I am hoping you will continue to improve. My next Rituximab (my first maintenance infusion) will be on 12/3 and I'll post about it in my Ritux thread. It is now a 4-month interval for me (vs. a 3-month interval) and I have not had any IVIG since July and no return of symptoms.

 

[Blake2e]

Update: yesterday got IVIG infusion #5 with the dose increased to 30g. Reaction was pretty mild for some reason. Rituxan helping? Feels like I'm getting better in some ways and worse in other ways. EMF sensitivity seems like its getting worse but I also seem to be responding to steroids slightly better and food reactions are a little more milder. Still have alternating diarrhea/constipation, terrible sleep and other allergy symptoms.

Also had Xolair #12 couple days ago, dose was increased from 300mg to 375mg.

Did blood work for Rituxan right before IVIG infusion. Got some of the results back already. My immunoglobulins are all down a decent amount. IgE quantitative serum is down most significantly, from over 1000 to 283. Amazing change. Need it to go down more. Brain function not yet good enough and drugs/supplements still arent getting absorbed too well.

Graduation is around the corner and I have a bunch of big tests and job interviews coming up. Need to speed up my recovery. Once I can get consistent relief with antihistamines/mast cell stabilizers and other drugs/sups then its pedal to the floor and marathon studying.

Hopefully [Rituxan] + [Xolair] + [IVIG] is my winning formula to manage/fix this problem.

Will see the results of the lymphoctye subset panel and CD27+ memory B cells in a day or so then decide if another Rituxan infusion is needed. I suspect it wont be needed until the maintenance dose. Next step will be to try to get my IVIG dose increased again for the next infusion.

(edited for grammar)

 

[Blake2e]

Update: Got blood work back. CD19 at 0.1% and abs at 1. Success on the Rituxan doing what it's suppose to do. CD27+ results arent clear for some reason the report says "see note" for all the results and then the note doesnt say anything. Gonna speak to dr to see what thats about.

Side note: has been 31 full days since end of Rituxan induction phase

 

[Gingergrrl]

@Blake2e I wanted to reply to your post earlier but was getting my first maintenance infusion of Rituximab on Mon. It was a very long infusion and my best friend was w/me and we both slept through about half of it! I haven't been on the computer in a couple days and am catching up on things now. I'm going to update my Ritux thread soon and my infusion went well.

Update: yesterday got IVIG infusion #5 with the dose increased to 30g. Reaction was pretty mild for some reason.

That is great that your reaction was mild. My IVIG was 27.3 grams each day in a 3-day cycle (total of 82 grams). Once in a while I would have a mild reaction but it was usually pretty bad. I just got used to it b/c the pay-off was worth it (in my case).

IgE quantitative serum is down most significantly, from over 1000 to 283. Amazing change.

Wow, that is an amazing change! I am now very curious what my own IgE is but have not tested it in quite a while.

Graduation is around the corner and I have a bunch of big tests and job interviews coming up. Need to speed up my recovery. Once I can get consistent relief with antihistamines/ mast cell stabilizers and other drugs/sups then its pedal to the floor and marathon studying.

I literally cannot even fathom going to work or school while I was getting IVIG and Rituximab. You are a rock star

Hopefully [Rituxan] + [Xolair] + [IVIG] is my winning formula to manage/fix this problem.

I hope so. I have never tried Xolair but IVIG & Ritux were the winning formula for me.

Update: Got blood work back. CD19 at 0.1% and abs at 1.

What do you mean that "abs were at 1"? Which autoantibodies are you referring to? I assume this is a different test from the Lymphocyte Subset Panel?

Side note: has been 31 full days since end of Rituxan induction phase

I was also curious what you meant by the "Rituxan induction phase"? I know there are several different autoimmune protocols and different doctor's use different terms. Do you mean the initial two infusions (at Day 0 and Day 14) or something else?

I completed the initial six infusions on Aug 3, 2018 (which took exactly one year) and just had my first maintenance infusion on Dec 3, 2018 (so we stretched out the interval from every 3-months to 4-months). If all goes well, we hope to stretch out the next interval to 5-months but much too early to predict yet how everything will turn out.

Best of luck you moving forward.

 

[Blake2e]

@Blake2e[/USER] I wanted to reply to your post earlier but was getting my first maintenance infusion of Rituximab on Mon. It was a very long infusion and my best friend was w/me and we both slept through about half of it! I haven't been on the computer in a couple days and am catching up on things now. I'm going to update my Ritux thread soon and my infusion went well.

Thats awesome that you slept through it means that it was an easy infusion. Cant wait to read your update!

That is great that your reaction was mild. My IVIG was 27.3 grams each day in a 3-day cycle (total of 82 grams). Once in a while I would have a mild reaction but it was usually pretty bad. I just got used to it b/c the pay-off was worth it (in my case)

Thats what I did for the last Rituxan infusion where I was reacting to the saline. Rough stuff, hopefully it doesnt happen at the maintenance.

Wow, that is an amazing change! I am now very curious what my own IgE is but have not tested it in quite a while.

Get it tested, interesting to see what it is. Its likely gonna be very low.

I literally cannot even fathom going to work or school while I was getting IVIG and Rituximab. You are a rock star

Thanks! I worked my butt off getting into this school/profession and absolutely nothing is going to stop me and I'll push through anything.

What do you mean that "abs were at 1"? Which autoantibodies are you referring to? I assume this is a different test from the Lymphocyte Subset Panel?

The absolute number of CD19 markers was a 1 and the CD19 %-age was 0.1, indicating the Rituxan did its thing. Its part of the Lymphocyte subset panel. As far as I'm aware I dont have any autoantibodies.

I was also curious what you meant by the "Rituxan induction phase"? I know there are several different autoimmune protocols and different doctor's use different terms. Do you mean the initial two infusions (at Day 0 and Day 14) or something else?

I completed the initial six infusions on Aug 3, 2018 (which took exactly one year) and just had my first maintenance infusion on Dec 3, 2018 (so we stretched out the interval from every 3-months to 4-months). If all goes well, we hope to stretch out the next interval to 5-months but much too early to predict yet how everything will turn out.

Best of luck you moving forward.

By induction I just mean the 2 initial doses that were 14 days apart. You probably told me already, but was the reason you were doing Rituxan every 3 months b/c your blood work showed your B cells weren't suppressed enough? What blood work are you using to monitor when you'd need another Rituxan dose, just the lymphocyte subset panel? I did the CD27 memory B cells blood work but b/c my B cells were so suppressed they couldnt get any results from it. I plan to do the lymphocyte subset panel and CD27 every month to keep a close eye on things.

 

[Gingergrrl]

Thats awesome that you slept through it means that it was an easy infusion. Cant wait to read your update!

Thanks and I haven't had a chance to write it yet but definitely will in the next few days.

Thats what I did for the last Rituxan infusion where I was reacting to the saline. Rough stuff, hopefully it doesnt happen at the maintenance.

Sorry, I need to explain what I meant re: the IVIG b/c I think what I wrote wasn't clear. I never had a reaction during an IVIG infusion at any point during the two years that I did IVIG. But I always had a delayed reaction and sometimes the delayed reaction was mild but usually it was pretty brutal (the "IVIG headache" & intra-cranial pressure, neck stiffness, muscle pain, and immune reaction w/chills, feeling feverish, etc).

Get it tested, interesting to see what it is. Its likely gonna be very low.

I will definitely let you know what it is when I next get it tested (but am not sure when that will be).

Thanks! I worked my butt off getting into this school/profession and absolutely nothing is going to stop me and I'll push through anything.

I totally understand and I loved my career more than anything. I worked in my career for 16 years prior to this illness ending it in early 2014. I was sick for all of 2013 but I continued to push myself until I could no longer walk from the parking lot to my office. At that point, if I would pushed myself further, I would have physically collapsed in the street from the severe POTS/tachycardia, muscle weakness, shortness of breath, and chest pain. And this was all prior to the MCAS and anaphylaxis starting up in 2015.

I had absolutely no idea what was wrong with me, and pursued several medical treatments and paths that were completely wrong before finding the right one. I am hoping to return to my career by the end of 2019 but honestly do not know if this is realistic. I plan to start with doing volunteer work and getting the CEU's needed to re-instate my license (two years worth)!

The absolute number of CD19 markers was a 1 and the CD19 %-age was 0.1, indicating the Rituxan did its thing. Its part of the Lymphocyte subset panel. As far as I'm aware I dont have any autoantibodies.

Thank you and that totally makes sense. You meant "abs" to mean the absolute number vs. the percentage of CD19. I always use "abs" to refer to "antibodies" or "auto abs" to refer to "autoantibodies" and that is what I thought you meant. Sorry for my confusion!

By induction I just mean the 2 initial doses that were 14 days apart.

That is what I thought you meant but I hadn't heard the term "induction" before so I wanted to be sure. So you meant that you are now 31 days past the loading dose or induction? Does that mean that you will not be having additional infusions every three months (or at some other interval determined by your doctor)?

You probably told me already, but was the reason you were doing Rituxan every 3 months b/c your blood work showed your B cells weren't suppressed enough?

Actually it wasn't. My doctor wanted me to do the "Autoimmune Protocol" which was the loading dose/induction at Day 0 and Day 14, and then every three months for a total of six infusions (which time-wise equaled one year). My B cells were always at zero every time we checked throughout that year. For me the loading dose was based on the BSA (body surface area) formula and was 600 mg of Ritux for each infusion.

What blood work are you using to monitor when you'd need another Rituxan dose, just the lymphocyte subset panel?

I think we did a CBC along with the Lymphocyte Subset Panel. We often checked for various other issues that pertained to my case but to monitor B cells, it was the Lymphocyte Subset Panel.

I did the CD27 memory B cells blood work but b/c my B cells were so suppressed they couldnt get any results from it.

What does that mean? If your B cells were at zero I assume this is good but how did you know they were too suppressed? (I have never done the CD27 memory B cell blood test and already forgot what this entails even though I know that you told me ).

I plan to do the lymphocyte subset panel and CD27 every month to keep a close eye on things.

I think I did the LSP every three months and after the initial two doses, my doctor didn't feel that there was any benefit to doing it more frequently.

 

[Blake2e]

I will definitely let you know what it is when I next get it tested (but am not sure when that will be).

Dont sweat it, if youre not having MCAS issues anymore than its not really that important to do.

I totally understand and I loved my career more than anything. I worked in my career for 16 years prior to this illness ending it in early 2014. I was sick for all of 2013 but I continued to push myself until I could no longer walk from the parking lot to my office. At that point, if I would pushed myself further, I would have physically collapsed in the street from the severe POTS/tachycardia, muscle weakness, shortness of breath, and chest pain. And this was all prior to the MCAS and anaphylaxis starting up in 2015.

I had absolutely no idea what was wrong with me, and pursued several medical treatments and paths that were completely wrong before finding the right one. I am hoping to return to my career by the end of 2019 but honestly do not know if this is realistic. I plan to start with doing volunteer work and getting the CEU's needed to re-instate my license (two years worth)!

I can totally empathize. There were so many moments where I was how the heck can I continue and every time I would try a new drug or something that allowed me to keep going at the last minute, moments before I was going to submit an official medical leave to my school. Luckily so far I can keep going.

Really do hope youll be back doing what you want again. Are you in the medical field? Also what makes you think you may not be able to return to work, is motor function not recovered enough yet?

That is what I thought you meant but I hadn't heard the term "induction" before so I wanted to be sure. So you meant that you are now 31 days past the loading dose or induction? Does that mean that you will not be having additional infusions every three months (or at some other interval determined by your doctor)?

Sorry I was using chemo jargon. But loading phase also works. Yep, as of today 34 days past the loading/induction phase. They havent said anything about any schedule yet. But it seems like it will be a monitor then decide situation. I'll likely have it every 4-6 months.

What does that mean? If your B cells were at zero I assume this is good but how did you know they were too suppressed? (I have never done the CD27 memory B cell blood test and already forgot what this entails even though I know that you told me ).

I think it just means that with the level of B cells the Rituxan brought me to there wasnt enough memory B cells around for the CD27+ test to pick up on. I imagine as my B cells start to repopulate the CD27+ test will pick up on it.

I think I did the LSP every three months and after the initial two doses, my doctor didn't feel that there was any benefit to doing it more frequently.

Theyre probably right, but I think its safer for me (and more comforting) if I'm watching everything like a hawk so nothing catches me by surprise. And also I'm monitoring a bunch of other things so bunching with LSP is just a little more blood out of me, no big deal.

 

[Gingergrrl]

Dont sweat it, if youre not having MCAS issues anymore than its not really that important to do.

I know that my MCAS doctor or main doctor will eventually test my IgE again as part of regular monitoring.

I am now curious, did you ever have elevated IgM? Mine was elevated for several years and we kept monitoring it and then my main doctor decided that we needed to make sure it was not due to cancer in light of my total picture. So he ordered some special testing (blood & urine) to rule out MGUS and cancer and it was all negative which was a relief! He now assumes that the elevated IgM was due to autoimmunity (and at my last test, for the first time, my IgM was in the normal range)! Not sure if this is related to my overall remission from IVIG and Ritux or unrelated.

I can totally empathize. There were so many moments where I was how the heck can I continue and every time I would try a new drug or something that allowed me to keep going at the last minute, moments before I was going to submit an official medical leave to my school. Luckily so far I can keep going.

That is great news that you were able to continue with school and I hope that this will only improve.

Really do hope youll be back doing what you want again. Are you in the medical field? Also what makes you think you may not be able to return to work, is motor function not recovered enough yet?

Thank you so much! I am an LCSW (licensed clinical social worker) and I did work in the medical field for many years but worked in many other areas of social work as well. This illness ended my career in 2014 and I had thought it was forever but now I believe that I might be able to work again in the future which is unbelievable!

The reason I have doubts if I am physically ready to return to work is that I have only been walking without a wheelchair and driving my car since May of this year (after 3.5 years of being completely disabled, for lack of a better word). My main doctor does not know what happens to me when I stop Rituximab and B-cells return. If I had an absolute guarantee (which is impossible) that this remission was permanent, I would feel confident to give up my disability/insurance and attempt to work full-time.

But there is no guarantee that this remission will not end and I need a (financial) back-up plan. At present, I am able to do all of my self-care, all of my shopping & errands, take care of my dog, take care of my step-daughter and cook her dinner and drive her to school on the nights/mornings that she is with me, go to weekly PT & Rehab Pilates to continue to build all of the muscle strength that I lost, go to doctor appts, etc. But this is without working and I could not do any of this by myself prior to May (and had a caregiver twice a week)! If I had to do all of this on my own and work at the same time, I do not know if my illness would start to return.

I do not know how far to push it but I feel the best way is to proceed in a graduated fashion (and I do NOT mean like "GET" and am not talking about exercise)! I mean re: work, to start with volunteer work 1-2x a week and starting to take the classes to get the 2 years worth of CEU's to put my license back on active status. If I can physically maintain my current level of activity, plus doing volunteer work and CEU classes, then I can take it up a notch, etc. I'm completely in unknown territory and each thing I thought was solid and permanent in the past turned out not to be.

Six years ago, I had thought my health, career and marriage were forever but none of them were. Then I finally accepted that this illness was progressive and being in a wheelchair was permanent (until I finally found the right treatments w/IVIG and Rituximab and it started to reverse). Now I am in this remission, and I'd like to believe it is permanent, but I am so uncertain b/c it may solely be maintained by Rituximab and having my B cells at zero. The ideal scenario is that my body has healed and it is now maintaining itself on it's own but I don't know that for sure, and neither does my doctor who is a brilliant physician (even though I am biased)!

Wow, sorry I did not mean to type a novel here! I started answering this thread about 4 hours ago and am now back while my daughter is doing some homework and am typing this in between quizzing her for an exam tomorrow.

Sorry I was using chemo jargon.

No worries and the chemo jargon works! My infusion center is actually a cancer center (but they treat autoimmune patients, MCAS patients, and many other illnesses, too).

Yep, as of today 34 days past the loading/induction phase. They havent said anything about any schedule yet. But it seems like it will be a monitor then decide situation. I'll likely have it every 4-6 months.

That is interesting that it is being decided as you go. My doctor decided that I would do a series of six Ritux infusions (the two induction doses, and then four more at a 3-month interval). If I was allergic, or did not tolerate the initial doses, we would have stopped. Also, if I did not have any response whatsoever after the 3rd or 4th infusion, we also probably would have stopped. But since it was crystal clear that I was a responder, we continued with the original plan. And now with the maintenance doses, we are monitoring (both B-cells and any return of symptoms) to figure out the ideal interval.

I think it just means that with the level of B cells the Rituxan brought me to there wasnt enough memory B cells around for the CD27+ test to pick up on. I imagine as my B cells start to repopulate the CD27+ test will pick up on it.

That makes sense.

Theyre probably right, but I think its safer for me (and more comforting) if I'm watching everything like a hawk so nothing catches me by surprise. And also I'm monitoring a bunch of other things so bunching with LSP is just a little more blood out of me, no big deal.

I agree. I can't remember if I already told you this but my doctor said that it is better to do the LSP at Quest b/c it tells you if the CD19 is actually zero vs. at LabCorp it tells you if it is <1 (which means it might truly be zero or it might be starting to grow back). I didn't know this until after my last test which was at LabCorp. It said both Abs and % of CD19 were <1 so I thought they were growing back but my doctor said this was not necessarily true and to do the next one at Quest. Hope that made sense!

 

[Blake2e]

I know that my MCAS doctor or main doctor will eventually test my IgE again as part of regular monitoring.

I am now curious, did you ever have elevated IgM? Mine was elevated for several years and we kept monitoring it and then my main doctor decided that we needed to make sure it was not due to cancer in light of my total picture. So he ordered some special testing (blood & urine) to rule out MGUS and cancer and it was all negative which was a relief! He now assumes that the elevated IgM was due to autoimmunity (and at my last test, for the first time, my IgM was in the normal range)! Not sure if this is related to my overall remission from IVIG and Ritux or unrelated.

My IgM has actually dropped a bit since starting Rituxan from 79 (May 15, 2018) to 56 (Nov 30, 2018). Still within normal limits. So I think its fine. How high was your IgM? But thank goodness cancer and gammopathy were ruled out.

Thank you so much! I am an LCSW (licensed clinical social worker) and I did work in the medical field for many years but worked in many other areas of social work as well. This illness ended my career in 2014 and I had thought it was forever but now I believe that I will be able to work again in the future which is unbelievable!

Interesting, so your work is a little similar to what you do on this forum when you provide emotional and practical support.

The reason I have doubts if I am physically ready to return to work is that I have only been walking without a wheelchair and driving my car since May of this year (after 3.5 years of being completely disabled, for lack of a better word). My main doctor does not know what happens to me when I stop Rituximab and B-cells return. If I had an absolute guarantee (which is impossible) that this remission was permanent, I would feel confident to give up my disability/insurance and attempt to work full-time.

That is a tough spot. On the one hand if you go back to work disability/insurance would be gone and if symptoms returned that would be a tremendous burden since you would have to deal with so much on your own. On the other hand, if you didnt go back to work you will have the insurance to cover for more treatment.

But there is no guarantee that this remission will not end and I need a (financial) back-up plan. At present, I am able to do all of my self-care, all of my shopping & errands, take care of my dog, take care of my step-daughter and cook her dinner and drive her to school on the nights/mornings that she is with me, go to weekly PT & Rehab Pilates to continue to build all of the muscle strength that I lost, go to doctor appts, etc. But this is without working and I could not do any of this by myself prior to May (and had a caregiver twice a week)! If I had to do all of this on my own and work at the same time, I do not know if my illness would start to return.

I personally think it would probably be better in your case to remain out of work for now. Observe how the Rituxan is working for you, possibly extend the time b/w maintenance doses and observe if any symptoms return/worsen. From my perspective it doesnt seem like there is much upside to going back to work, aside from it being a job you enjoy. If you go back to work insurance can become a huge issue, you would get to spend less time with your family (something you probably couldnt properly enjoy while being so symptomatic), and the high stress of trying to do everything (balancing work, family and managing your health). The only good reason I could see for going back to work is if you really need the extra income.

I do not know how far to push it but I feel the best way is to proceed in a graduated fashion (and I do NOT mean like "GET" and am not talking about exercise)! I mean re: work, to start with volunteer work 1-2x a week and starting to take the classes to get the 2 years worth of CEU's to put my license back on active status. If I can physically maintain my current level of activity, plus doing volunteer work and CEU classes, then I can take it up a notch, etc. I'm completely in unknown territory and each thing I thought was solid and permanent in the past turned out not to be.

I like that a lot. Ease into it and observe how your body reacts. And when you find stability where health is good and you can work then you can sign up for a new insurance plan.

Six years ago, I had thought my health, career and marriage were forever but none of them were. Then I finally accepted that this illness was progressive and being in a wheelchair was permanent (until I finally found the right treatments w/IVIG and Rituximab and it started to reverse). Now I am in this remission, and I'd like to believe it is permanent, but I am so uncertain b/c it may solely be maintained by Rituximab and having my B cells at zero. The ideal scenario is that my body has healed and it is now maintaining itself on it's own but I don't know that for sure, and neither does my doctor who is a brilliant physician (even though I am biased)!

The unknown is quite a thing. I hope it is permanent. I've read cases where people extended their maintenance dose to once a year or longer. At that time range I think a good amount of the downsides of Rituxan go down. Then eventually if its extended that long then completely stopping treatment can become a possibility.

Wow, sorry I did not mean to type a novel here! I started answering this thread about 4 hours ago and am now back while my daughter is doing some homework and am typing this in between quizzing her for an exam tomorrow.

It's all good. Strangely enough I was also just helping my baby sister with her homework.

That is interesting that it is being decided as you go. My doctor decided that I would do a series of six Ritux infusions (the two induction doses, and then four more at a 3-month interval). If I was allergic, or did not tolerate the initial doses, we would have stopped. Also, if I did not have any response whatsoever after the 3rd or 4th infusion, we also probably would have stopped. But since it was crystal clear that I was a responder, we continued with the original plan. And now with the maintenance doses, we are monitoring (both B-cells and any return of symptoms) to figure out the ideal interval.

I'm gonna contact my Immunologist and see what he says about timing of maintenance dose. I feel I am clearly a responder. My serum IgE have dropped significantly. Before Rituxan steroids were losing all effectiveness for me and after Rituxan all of my allergies have dropped noticeably (still very troublesome but a bit less so) and steroids are working for me (could be better but at least its helping).

I agree. I can't remember if I already told you this but my doctor said that it is better to do the LSP at Quest b/c it tells you if the CD19 is actually zero vs. at LabCorp it tells you if it is <1 (which means it might truly be zero or it might be starting to grow back). I didn't know this until after my last test which was at LabCorp. It said both Abs and % of CD19 were <1 so I thought they were growing back but my doctor said this was not necessarily true and to do the next one at Quest. Hope that made sense!

My blood work for LSP wasnt done through labcorp but the displayed results are no different from labcorp. I'm gonna ask my doc to specifically put that lab order through Quest next month.

 

[Gingergrrl]

My IgM has actually dropped a bit since starting Rituxan from 79 (May 15, 2018) to 56 (Nov 30, 2018). Still within normal limits. So I think its fine. How high was your IgM?

I just checked my records to make sure I have the numbers right and for many years my IgM was in the 300's. But for the first time it is now at 230 which is within the normal range. It's still on the higher side but much better.

But thank goodness cancer and gammopathy were ruled out.

Yes, that was a relief!

Interesting, so your work is a little similar to what you do on this forum when you provide emotional and practical support.

I guess so but it was so different doing both clinical work and advocacy in person and I really miss it. If I am able to work again in the future (in any capacity), I want to work with what I now call the "hidden illness community" (all of us). There is such an unmet need although I am still unsure exactly how I would be the most useful.

That is a tough spot. On the one hand if you go back to work disability/insurance would be gone and if symptoms returned that would be a tremendous burden since you would have to deal with so much on your own. On the other hand, if you didnt go back to work you will have the insurance to cover for more treatment.

I might start a new thread on this topic of going back to work (not tonight, but hopefully soon). I want to do that both so I do not take your thread further off track from talking about your experiences with IVIG and Rituximab but also so I can discuss it in the Members Only section. Thank you so much for discussing all of this with me, it was so kind of you to take the time to do that!

I personally think it would probably be better in your case to remain out of work for now. Observe how the Rituxan is working for you, possibly extend the time b/w maintenance doses and observe if any symptoms return/worsen.

This honestly sounds like the smartest plan the more that I think about it.

The unknown is quite a thing. I hope it is permanent. I've read cases where people extended their maintenance dose to once a year or longer.

That would be amazing.

It's all good. Strangely enough I was also just helping my baby sister with her homework.

What a coincidence and you sound like a great older brother.

I'm gonna contact my Immunologist and see what he says about timing of maintenance dose. I feel I am clearly a responder.

It sounds like you are a responder and it makes sense to talk to your immunologist and figure out a tentative schedule for future doses so you can plan ahead.

My blood work for LSP wasnt done through labcorp but the displayed results are no different from labcorp. I'm gonna ask my doc to specifically put that lab order through Quest next month.

My doctor definitely wanted me to do it at Quest next time but I would also ask your doctor about it in case there are other tests that he prefers at a different lab (since you are doing that CD27 test and other ones that I have not done).

 

[Blake2e]

Update: Just about 3 months since finishing Rituxan loading phase. It felt like it was working initially, my steroids were working better and I was able to temporarily lower my steroids dosages. But now my steroids dosages are coming back up and may soon be ineffective for me. My IgE is rising every month at a concerning rate.

The Rituxan removed almost all the B cells so new allergies shouldn’t develop as long as my B cells remain ablated. One part of the puzzle is in place (antigen-specific IgE+ memory B cells are depleted by Rituxan) but the other part (long-lived IgE plasma cells) are still causing havoc.

I need a solution to remove the long-lived plasma cells.

 

[Blake2e]

Possibility #1 to handle IgE produced by long-lived IgE plasma cells

Mechanisms of actions for high dose IVIG:

1) Functional blockade of immunoglobulin E receptors on mast cell membranes.

2) Inhibition of complement mediated damage and modulation of the cytokines/cytokine antagonists’ production. Decreasing Th2 dominance.

3) Neutralization of circulating autoantibodies (if I have autoantibodies) by anti-idiotypic antibodies present in high-dose intravenous immunoglobulin.

4) An additional trigger for mast cell activation includes T-cell activity and release of microparticles and cytokines. IVIG increases regulatory T-cells which could reduce T-cell activity and thereby reduce mast cell activity.

5) IgG has been found to downregulate IgE bound to mast cells and thus binding IgG by IVIG could play an additional role.

6) Increases glucocorticoid sensitivity (thus decreasing steroid dosage needed and may help with autonomic dysfunction): IVIG increases glucocorticoid receptor binding may occur indirectly, since IVIG decreases production of the two cytokines known to alter glucocorticoid receptor binding – IL‐2 and IL‐4.

7) Administration of high‐dose IVIG may provide circulating antibodies which bind to IgE and remove them from the circulation.

8) IVIG at high doses has many more anti‐inflammatory and immunomodulatory effects

***

Sources for #1-4: “Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment” (https://casereports.bmj.com/content/casereports/2018/bcr-2017-221405.full.pdf)

“Solar urticaria treated successfully with intravenous high-dose immunoglobulin: a case report” (full paper attached)

Source for #5: “IgG-mediated down-regulation of IgE bound to mast cells: a potential novel mechanism of allergen-specific desensitization” (full paper attached)

Source for #6 and 7: The role of immunoglobulin therapy in allergic diseases (https://onlinelibrary.wiley.com/doi/full/10.1034/j.1398-9995.1999.00094.x)


Other studies relating to mechanisms:

“Effect of high-dose intravenous immunoglobulin treatment in therapy-resistant chronic spontaneous urticaria” (Full paper attached)

“Role of Treg in immune regulation of allergic diseases” (Full paper attached)

“High‐dose, but not low‐dose, IVIg treatment enhanced the activation status of circulating Tregs” (https://onlinelibrary.wiley.com/doi/full/10.1111/cei.12102)

"The IgG molecule as a biological immune response modifier: Mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders" (Full paper attached) (More mechanisms, pg 3)

 

[Blake2e]

“We demonstrated that B-cell depletion induced the differentiation of short-lived auto-immune plasma cells into long-lived ones in the spleen.” (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873528/) This may explain why the partial response I felt initially began to wane.

*** “Pathogenic Long-Lived Plasma Cells and Their Survival Niches in Autoimmunity, Malignancy, and Allergy” (http://www.jimmunol.org/content/189/11/5105)
Even with immunosuppression depleting B cells, long-lived plasma cells are still an issue. Solution: target plasma cell directly or their survival niche. Study lists many way to decrease the problem of long-live plasma cells.


Possibility #2 to deal with long-lived IgE plasma cells: Proteasome Inhibitor (Carfilzomib) with HDAC drugs:

Great intro for how it works: https://www.myelomacrowd.org/myeloma-101-proteasome-inhibitors-work/

Carfilzomib is a second-generation proteasome inhibitor with a low neuropathic risk.

[I'm still accumulating and sorting studies. Will add to this post later. Gist of it is is that this combination of drugs will directly decrease plasma cell populations]