Immune Paralysis

[Buster]

A number of people have been asking about what causes a failure of PREVNAR serotype antibody response despite a full vaccination schedule.

 

There's a very good paper on pneumococcal unresponsiveness from the UK:

 

http://www.ncbi.nlm.nih.gov/pmc/articles/P...pdf/0796-08.pdf

 

 

The abstract is:

Following the introduction of the pneumococcal 7-valent conjugate vaccine (PCV7) into the routine infant immunization schedule in England, Wales, and Northern Ireland, pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered as a clinical service to all children within the program with invasive pneumococcal disease (IPD) to confirm an adequate antibody response to PCV7. As of March 2008, serum samples taken within 14 to 90 days of vaccination had been submitted from 107 children who had received one or more doses in the second year of life. Sera were assayed by a multiplexed microsphere assay incorporating both cell wall polysaccharide and serotype 22F adsorption. A protective serotype-specific antibody level was defined as a concentration of >0.35 g/ml. Eight children failed to develop a response to their infecting serotype (6B [n 4], 18C [n 2], 4 [n 1], and 14 [n 1]), despite receiving at least three doses of PCV7 in the second year of life or two doses in the second and two or three in the first year of life. A further two children were nonresponsive to a serotype (6B) different than that causing disease. None of the 10 children had a clinical risk factor for IPD. Two had marginally low levels of total serum IgG but mounted adequate responses to the other six PCV serotypes. This serotype-specific unresponsiveness may reflect immune paralysis due to large pneumococcal polysaccharide antigen loads and/or a potential genetic basis for nonresponse to individual pneumococcal serotypes.

 

The basic comment was that "Failure to respond adequately to their infecting serotype may potentially be explained by large pneumococcal polysaccharide loads interacting and then depressing the immune system’s ability to respond by depleting the memory B-cell pool."

 

I personally found this interesting that your body can essentially be depleted of memory B-cells due to load of antigen.

 

Buster

[P_Mom]

Thanks, Buster. This is extremely interesting to me. I need to read it a couple more times to be sure I got it. What is interesting to me is that this states that 0.35 is protective....with docs here saying you need atleast 1.0 (some say 2.0) to be protected. I think that is important and can change things....it makes my borderline kids pass with flying colors. It also stated that marginally low total IGG is of little significance in these kids...atleast that is what I got from my scan so far.

 

What is your take on this?

[sf_mom]

You are the best..... I'll be dragging this with on Thursday to the Dr.

 

-Wendy

[Buster]

I contacted one of the author when this came out. They indicated that a value > .30 is considered a response. I have another reference that shows the PREVNAR values per age group:

 

http://cvi.asm.org/cgi/reprint/14/11/1442

 

What was interesting to me was the introduction of a paralysis in the immune response.

 

I'm absolutely not saying this is happening in PANDAS, but found it interesting none-the-less. So for those having PID, perhaps this immune paralysis is what is going on.

 

Buster

 

 

Thanks, Buster. This is extremely interesting to me. I need to read it a couple more times to be sure I got it. What is interesting to me is that this states that 0.35 is protective....with docs here saying you need atleast 1.0 (some say 2.0) to be protected. I think that is important and can change things....it makes my borderline kids pass with flying colors. It also stated that marginally low total IGG is of little significance in these kids...atleast that is what I got from my scan so far.

 

What is your take on this?

[nevergiveup]

P. Mom,

Its not about being protective or not protective its whether the child's immune systems can mount a response. If a doc is wanting to diagnose SAD then low IGG is not critical. But for CVID the pneumoccal serotypes are not needed for this diagnosis but many immune docs want to see low levels IGG with bad immune responsiveness. However again, two different diagnosis SAD is part of the polysacharroid def and CVID is IGG based. And again without chronic infection none of this truly matters. Some docs feel any response above 2 on any serotype means the child is protected and can mount a response. (It takes only 1 serotype above 2, the rest can be zero).

You'd know if your kid has an immune def long before any testing, these kids are sick a lot.

 

Thanks, Buster. This is extremely interesting to me. I need to read it a couple more times to be sure I got it. What is interesting to me is that this states that 0.35 is protective....with docs here saying you need atleast 1.0 (some say 2.0) to be protected. I think that is important and can change things....it makes my borderline kids pass with flying colors. It also stated that marginally low total IGG is of little significance in these kids...atleast that is what I got from my scan so far.

 

What is your take on this?

[P_Mom]

How do they determine a response...I mean..what do the titers mean....protected...or mounted response??

 

Do they take the blood sample and then expose it to the different bacterial strains?? If so, then the titer level of antibody measured would be the response they mounted to the particular strain..right? So then, that level of mounted response, if above 0.35, would be protective...and, a sufficient mounted response. lol Follow me?

 

This still, in my mind, would show passing mounted responses for many children who have been otherwise told they failed the s. pneumonia titers.........which is a huge discussion on here with many different opinions.....you almost always hear...."my child failed the s. pneumonia titers"....but, did they really? Sorry, but I am still not (now even more so) feeling the s. pneumonia titers to be significant. Please, just my opinion.....I already know many disagree.

 

Also, Buster stated he contacted one of the authors and they stated that just greater than .30 is considered a response!

A big difference from what I had been hearing! That is all I am trying to get across.

[Buster]

Hi P.Mom,

 

That was sort of the reason I posted the two papers -- I have a few more on this topic if you'd like.

 

In the first paper I posted, they drew blood within 18 m of a revaccination and looked at the antibody responses using 2 different ELISAs. The response was measure to a challenge of the revax.

 

In the second paper, the titers were pulled pre-vaccination -- trying to get a sense of the baseline numbers. You'll see that several serotypes never had been presented so there was no response.

 

I've spoken with several immunologists regarding "baseline titers" and frankly they don't seem to know. It does seem remarkable to me that this vaccine could have so much use and not have good data on the duration of protection past 18m post last vaccination.

 

What seems consistent is that the expected response to a new challenge (i.e., revax) is a 4-10x rise in titers for the serotypes. Without revax the beliefs about how much should be in the baseline values are all over the place (and frankly it doesn't seem to be well researched).

 

The difficulty for probably most parents here is that now that you're on the PANDAS path and now you find the lower than expected Pneumococcal serotype antibodies... do you revaccinate and check the titers or leave things alone. In our case, we had no desire to be experimenting with the reintroduction of a vaccine in the middle of the auto-antibody issues.

 

 

Also, Buster stated he contacted one of the authors and they stated that just greater than .30 is considered a response!

A big difference from what I had been hearing! That is all I am trying to get across.

 

I agree that in the US, most doctors are looking for a rise to a value > 1.2 (i.e., 4x .4). The question is whether you let the doc revax to check for the value or not. We decided not.

 

As they say, clear as mud...

 

Buster

[peglem]

We did the vaccine titer challenge about 2 1/2 years ago, but with pneumovax- my daughter had never had prevnar. Baseline for the 14 serotypes (I think it was 14) was <2.0 for all but 3 serotypes. 2 weeks post vaccine showed almost no response...So, we revaxed and 14 days later there was a full response. Both vaccines were given a few days after finishing a course of antibiotics (although I don't remember which one) because the immuno did not want to give the vaccine when my daughter was positive for strep. So each time, I had to have her tested for strep 1st (she was positive both times) and then wait until the antibiotics were finished before vaxing. Now, 2 1/2 years later, those titers have fallen again. The immuno wanted to try vaxing again, but I said no...just couldn't see this time (now that I know) how it would help us figure anything out.

 

When we did the vax challenge, and got a titer rise from the second vaccine, the immuno reported that he'd "jump started" the immune system so it was responding now, and she should be having less trouble with strep now. The positives for strep continued though.

[P_Mom]

Buster....thanks. I would be interested in the other articles you have!

[sf_mom]

PMom.

 

I agree with Buster... clear as mud.

 

BUT, I happen to believe they might be more significant and not to rule them out yet. Here is why. The boy who had RF at playdate in 2007 and is now PANDAS.... We have labs from when he initially took ill with RF and 1 1/2 years later when he was still fighting strep. His Strep Pneumococcal Antibody Titers went down significantly during this period. I've inquired about it with every Dr. I've seen and even a streptologist and here is her response.

 

 

INFECTIONS SUCH AS PNEUMONIA AND MENINGITIS. THERE IS A VACCINE AVAILABLE THAT MANY CHILDREN HAVE RECEIVED IN THE PAST FEW YEARS, AND VACCINATION AFFECTS THE ANTIBODY TITERS. I SUSPECT THESE CHILDREN WERE NOT VACCINATED BASED ON THE LOW TITERS. THERE ARE 90 DIFFERENT TYPES OF PNEUMO, SO EVEN IF EACH CHILD HAD ONE OR A FEW PAST PNEUMO INFECTIONS (EAR, SINUSES), IT MAY NOT BE SURPRISING THAT THEIR TITERS ARE LOW.

 

-Wendy

[P_Mom]

The problem is that we have ALL inquired about it with every doc we have seen....and we have all seen A LOT. (I know I have).......they all do not agree. Actually, the vast majority of them have told me to pay no mind to the s. pnuemonia titers.(which does not measure s. pyogenes, or, group A strep) Obviously, it needs much more research.....until then, it seems to me it is up to us to investigate and decide for ourselves.

 

Depending on when this child you mention finished his Prevnar vaccines (was he vaccinated??).....anyway, the series is finished by two yeas of age, at the latest. After the series, the child spikes in titer levels, which is followed by a significant drop in levels after that. Then, the child slowly, over time, begins to rebuild. Could this have been occuring when the titers were taken? Just a thought.......please keep that in mind.

 

 

Personally, at this point, I am not putting much thought to them anymore. If 0.35 is "passing".....my kids passed them all and I believe are capable of mounting appropriate immune responses to the s. pneumonia strains.

 

I am actually not sure what the paragraph that doc you quoted is getting at.

 

Just my feelings....any parent who disagrees and wants to put stock in these values (and I am sure some are legitimate) can surely do so without my protest!

[sf_mom]

PMom: All kids were fully vaccinated and this particular boy was 5 and 6 1/2 when titers were checked and dropped significantly. I think its difficult to say at this point its meaning but willing to say 'it might mean something and it might mean nothing'. I've been trying to investigate further if s. pnuemonia titers only measure B antibodies because B can actually cause A. See below.

 

The type of hemolytic reaction displayed on blood agar has long been used to classify the streptococci. Beta -hemolysis is associated with complete lysis of red cells surrounding the colony, whereas alpha-hemolysis is a partial or "green" hemolysis associated with reduction of red cell hemoglobin. Nonhemolytic colonies have been termed gamma-hemolytic. Hemolysis is affected by the species and age of red cells, as well as by other properties of the base medium. Group A streptococci are nearly always beta-hemolytic; related Group B can manifest alpha, beta or gamma hemolysis. Most strains of S. pneumoniae are alpha-hemolytic but can cause ß-hemolysis during anaerobic incubation.

 

I will keep you posted if I find any significant......

[sf_mom]

Oh and I wanted to add....

 

Based on the theory my father-in-law mapped out. The S pyogenes is fought off through cross immunity to other strains of strep because of the lack of humoral response in a young child due to protease enzymes it secretes. Therefore the antibodies for other strains of strep would be utilized to attack this particular strain. Hence, potentially low strep pneumo titers.

 

Effect of SpeB and EndoS from Streptococcus Pyogenes on Human Immunoglobulins http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/

 

http://www.latitudes.org/forums/index.php?showtopic=6386

[sf_mom]

Again, I don't know if it means anything but I just got our son's Strep Pneumococcal Antibody Titers results this evening and they dropped in 1/2.... 12 of 14 serotypes in 30 days.

 

My 'mother's instincts' tell me, if he can show a protective status in all categories and sustain those numbers..... I'd feel comfortable saying he is winning the battle with the underlying infection and his immune system will have a chance to bounce back.

 

Lab results say protective status is 2.0 mcg. and shows him currently protective in 7 of 14 serotypes.

[P_Mom]

Are they the 7 he was vaccinated for?

 

Does your farther-in-law treat your children??