IgG2 deficiency in pregnant women and H1N1

[ema-adama]

http://www.bloomberg.com/apps/news?pid=20601202&sid=agSkfeIV2ryg

Blood tests on 16 healthy pregnant women used in the study for comparison found more than half were “mildly deficient” in an immunoglobulin G subclass, she said. The lowest IgG2 levels were recorded in the severely ill pregnant swine flu patients.So, they found IgG2 was deficient in some pregnant women. And treating them with IgG improves their condition.

So, I found this site:
http://www.xs4all.nl/~ednieuw/IgGsubclasses/subkl4.htm (http://www.xs4all.nl/%7Eednieuw/IgGsubclasses/subkl4.htm)

Since IgG2 is the predominant antibody isotype produced in response to some polysaccharide antigens, it is not surprising that patients with decreased IgG2 levels may have an impaired response to infections with encapsulated bacteria.

IgG2: In about half of all IgG subclass deficiencies the IgG2 concentrations are decreased. An isolated IgG2 deficiency is associated with decreased responses to infections with encapsulated bacteria and after immunisation with polysaccharide antigensSo I am wondering how a vaccine can help people with IgG2 deficiency. It looks like their humoral immune system is not responding adequately. Surely this means that people with who are IgG2 deficient would not respond to vaccines? Ie they have a decreased response to pneumococci, meningococci and Haemophilus influenza type B (HiB) vaccines, the very vaccines that are recommended foe secondary infection prevention.

Here is a partial answer:
http://www.xs4all.nl/~ednieuw/IgGsubclasses/subkl45.htm (http://www.xs4all.nl/%7Eednieuw/IgGsubclasses/subkl45.htm)

In IgG2-deficient patients, only a marginal compensating mechanism exists, as illustrated by the impaired anti-polysaccharide response in all other immunoglobulin isotypes. This poor responsiveness can be partly bypassed by using conjugate-vaccines.
Nevertheless, it should be kept in mind that active vaccination procedures may fail, due to a deficient humoral immunity. Now, searching for how IgG is produced, I found this:
http://www.jimmunol.org/cgi/content/abstract/109/6/1386


The Fab-anti-Fab assay for human IgG quantitation is used to measure in vitro IgG production by lymphocytes from five normal human lymphoid tissues: bone marrow, spleen, blood, lymph node and thymus. Synthesis of IgG was found to proceed at a constant rate over the 10-day culture period; production could be prevented by hypothermia or mitomycin-C. When corrected for total lymphoid cells, the bone marrow was noted to produce greater than 95% of the IgG synthesized by the organs which were evaluated. Secondary antigenic stimulation with smallpox vaccine resulted in accelerated IgG synthesis by blood and splenic lymphocytes; conversely, no response was noted in cultures containing marrow or thymic cells. It is concluded that the bone marrow must be considered as a major site of IgG production under normal circumstances; however, the inability of the bone marrow to respond to antigenic stimulation suggests that the appropriate quantity or quality of cells is lacking in this organ for optimal antigenic recognition and/or processing.Which has me wondering if this is a partial explanation for why vaccines do not produce a 'normal' immune response. Ie they tested the different tissues response to a small pox vaccine. Is there reason to think that the response would have been different if the tissues were responded to a 'real' disease and not a vaccine?

Also, any direction for reading on supporting production of IgG and conditions that impair production of IgG would be appreciated. Thanks

[ema-adama]

http://www.wjgnet.com/1007-9327/4/464.asp

Although the immunogenicity and protective effect of rHBsAg are comparable with that of HBV natural infection, differences have been described in IgG subclass distribution after infection or vaccination. The serological response to HBsAg has been well characterized in patients with acute or chronic hepatitis B, who presented circulating immunocomplexes containing mostly IgG1 and IgG4 antibodies, or in convalescent sera where specific antibodies were predominantly IgG1 and IgG3. The analysis of IgG subclass distribution induced by vaccination with rHBsAg shows that the IgG2 subclass is mainly synthesized with IgG1. The presence of IgG2 with IgG1 subclass following vaccination against HBV was also described using plasma-derived vaccines, where HBsAg is glycosylated. Although the synthesis of IgG2 subclass antibodies is generally associated with polysaccharide antigens, the absence of glycosylated residues in the rHBsAg cannot explain the switch to IgG2 production. A hypothesis to explain a comparable immunogenicity from both vaccines is that the network of cytokines secreted by T lymphocytes recognising natural or recombinant HBsAg, could induce the B lymphocyte switch to this IgG subclass synthesis

This is in relation to the Hep B shot - but I found it interesting that the immune response is again different when analysing the types of anitbodies from natural infection and from vaccination. And they don't know why it is different or what the significance of that difference is.

[ema-adama]

http://cvi.asm.org/cgi/content/full/11/3/631

We have observed that United Kingdom adults produce high H. pylori-specific IgG2 levels (indicating a Th1 reaction to H. pylori), whereas Gambian adults and children and United Kingdom children produce predominantly IgG1 (indicating a Th2 response). These data suggest that Gambians, who are challenged with H. pylori infection in childhood, maintain the Th2 response throughout life, whereas United Kingdom adults appear to convert to a Th1 response. European children may mount a gastric mucosal Th1 response to H. pylori (7 (http://cvi.asm.org/cgi/content/full/11/3/631#R7)), similar to adults (2 (http://cvi.asm.org/cgi/content/full/11/3/631#R2)). However, we have measured an apparent systemic Th2 response. This discrepancy between the mucosal and systemic responses may be explained by local regulatory responses, such as bystander suppression, mediated by transforming growth factor beta. Such a mechanism can selectively suppress local cell-mediated inflammation (6 (http://cvi.asm.org/cgi/content/full/11/3/631#R6)), encouraging a Th2 bias. This process, however, requires a continual mucosal challenge, which is not sustained in United Kingdom children, allowing a Th1 phenotype to develop. This Th1 bias may be associated with gastric carcinogenesis (3 (http://cvi.asm.org/cgi/content/full/11/3/631#R3)).
The bias in IgG2 production in United Kingdom adults is consistent with the hypothesis that a shift in polarity of T-helper-cell responses in chronic H. pylori infection could provide an explanation for the apparent difference in prevalence of H. pylori-associated gastric carcinoma between West African and European populations. These results require confirmation with direct studies of gastric mucosa in these four groups of subjects. The factors involved in the reversal of T-helper-cell polarity in United Kingdom children to one that leads to gastric cancer are unknown but are likely to include bacterial factors, host genetics, and coexistent enteropathy (5 (http://cvi.asm.org/cgi/content/full/11/3/631#R5)).
Conventional vaccines have failed to eradicate H. pylori, but this study highlights differences in immune responses associated with populations with high and low risks of gastric cancer. Identifying those factors that lead to a reversal of the African phenotype to the cancer-prone United Kingdom phenotype could allow immunomodulation to achieve the elusive goal of preventing H. pylori-associated gastric cancer.

Not the flu, but this is interesting. So, IgG1 is a Th2 response and IgG2 is a Th1 response? This is getting more and more interesting.

[ema-adama]

: Vet Res Commun. (javascript:AL_get(this,%20'jour',%20'Vet%20Res%20 Commun.');) 2007 Aug;31 Suppl 1:103-7.http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3055&itool=AbstractPlus-def&uid=17682855&nlmid=8100520&db=pubmed&url=http://dx.doi.org/10.1007/s11259-007-0075-7) Links (javascript:PopUpMenu2_Set(Menu17682855);)
Parameters for evaluating the cell-mediated immune response during viral infection: diagnostic and prognostic applications.

Corradi A (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Corradi%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Ferrari L (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Ferrari%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Borghetti P (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Borghetti%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Department of Animal Health, Pathology Unit, Faculty of Veterinary Medicine, University of Parma, via del Taglio 8, 43100, Parma, Italy. attilio.corradi@unipr.it


I am a little all over the place - but this looks interesting too.....

[Momtezuma Tuatara]

The problem with any tests, is that you can only "test" or evaluate something that you understand. If you don't understand something, then you can't know what it's relevance is.

So for instance, because a woman's immune system is suppressed during pregnancy, to stop her body "rejecting" the baby which is essentially a graft (50% father) in her body, you would expect pregnant women to have a dampened down immune system. At all costs, her body suppressed rejection of the baby, which is an immune system driven process, and part of that will be that the inate arm of the immune system won't work as efficiently.

BUT the medical profession understands dotsquat about the inate immune system, so how can they put the Ig 2 deficiency into the context of the whole functioning body?

They can't. They are guessing, which might be right, but might be wrong, because there might be a whole lot of things which, because they don't yet understand, they can't either evaluate or measure.

[ema-adama]

Do you have any reading you can recommend on the innate immune system? Would you expect to see low IgG2 in all pregnant women?

Do you have any thoughts on the safety to the unborn fets when treating pregnant women with IgG.

Janeway CAJ seems to have done interesting work with the inate immune system, but I can't find any abstracts.

Please be patient with me, I am still learning.

[ema-adama]

I found this study: (sorry I don't know how to do a pdf version)

Immunobiology of gestational zinc deficiency (http://www.google.co.il/url?sa=t&source=web&ct=res&cd=2&url=http%3A%2F%2Fjournals.cambridge.org%2Fproducti on%2Faction%2FcjoGetFulltext%3Ffulltextid%3D891056&ei=WYnHSpPtMs-ZjAfzk91H&rct=j&q=igg2+deficiency+pregnancy+diet+supplement&usg=AFQjCNGR-Oegjkbk5BBdQ98o3x6Ma0EWhg&sig2=fplRy-mQKK6gPqYFThcjMA)



And here it mentions that a zinc deficiency in pregnant women results in decreased IgG2 in the infant, an imbalance that can be passed on to the next generation.

So it would be possible that the pregnant women with the IgG2 deficiency were born to zinc deficient mothers?

[Momtezuma Tuatara]

It's hard to know. They are making the assumption that the change is permanent, whereas I'd be asking whether or not it was epigenetic, and therefore could be "turned off".

i have no advice for pregnant women other than to eat correctly, and realise that the body is designed to work properly, if given the right nutrients to do so. the mother has to suppress her immune system in order not to lose the baby. Anything that runs counter to that, surely can't be a good thing.

When it's not broke, don't fix it. And as you've found, one simple nutrient deficiency can have interesting effects. And usually mothers who are zinc deficient are also "other nutrient" deficient. If folic acid deficiency can disrupt DNA replication, just think what all the other nutrient deficiencies can also do!

[Nirvana]

I thought this may interest you Ema-adama

http://cat.inist.fr/?aModele=afficheN&cpsidt=3155584

The effects of gestational Mg or Zn deficiency on the humoral or cellular immunity of newborn rats were investigated. Mg deficiency was induced by feeding a diet containing 180 ppm Mg from day 0 to day 21 of gestation and Zn deficiency was induced by feeding a diet containing 1.5 ppm Zn from day 0 to day 19. Controls were fed a diet with 1,000 ppm Mg and 100 ppm Zn from day 0 to day 21. Thereafter, all maternal rats and newborns were fed diets with normal amounts of Mg or Zn. Three and six weeks after birth, T-cell subpopulations in blood and thymus and B-cells in blood of the newborns were detected by flow cytometry. Plasma contents of IgG, IgM, and IgA were determined by radial immunodiffusion. Mg deficiency reduced litter size and pup weight. Three weeks after birth, the total number of leukocytes and lymphocytes in blood was significantly decreased, due to a reduction of T-helper and cytotoxic T-cells. Activated T-cells and B-cells were unchanged. Six weeks after birth, T-cell subpopulations approached controls values, whereas IgG content in plasma was slightly reduced. Gestational Zn deficiency reduced litter size and induced malformations. Three and six weeks after birth, body weight, number of leukocytes, lymphocyte, and T-cell subpopulations were not significantly changed. Plasma IgM was decreased 3 weeks after birth in correlation to the number of B-cells, which represented only 4% of total lymphocytes. These effects were repaired by the sixth week. Plasma IgG was reduced at 6 weeks. No effects on T-cell subpopulations in isolated thymocytes were detected after gestational Mg or Zn deficiency.

[ema-adama]

Yay, thanks for that :D