A blog reader, thank you!, sent me a 2007 study on IgE written by an Italian research team. The full study is available here: http://tinyurl.com/4do9nx.
Intriguing, I must say. As a myeloma patient, you tend to read mostly about IgG (my type of myeloma), IgA and IgM…but not much about the other immunoglobulins. I looked up IgE and found that it triggers our body’s response to allergens such as cat dander, dust mites and pollen, and it also protects us from parasitic worms.
Well, I’d never even thought of having my IgE levels tested, so I was particularly interested in this study. The “Discussion” part tells us that This is the first study reporting polyclonal IgE levels in a large series of MGUS subjects and MM patients. To the best of our knowledge, it is also the first study reporting an association between IgE levels and Hb, and, even more interestingly, between IgE levels and survival in patients with hematologic malignancies. (“Hb” stands for haemoglobin, by the way.)
IgE levels are connected to survival? Well, well. Let’s keep reading.
The Italian researchers checked IgE levels in a large number of myeloma patients and MGUS folks and compared the results to a control group in order to determine survival and prognostic factors. They found that IgE levels progressively decreased from controls to MGUS and from MGUS to MM. And patients with high IgE levels lived 2 to 3 years longer than those with low or intermediate levels.
They concluded that high IgE levels are positive predictors of overall survival (P = 0.03 and 0.08,respectively) and strongly correlated with hemoglobin values.
Problem is, though, that total IgE levels are highly variable in general population, depending on many factors, such as age, gender, race, atopy, genetics, immune status, season of the year, tobacco smoke, and concomitant diseases. Further on we read that the Ranges of normal IgE levels are very variable, and no consensus among laboratories has been reached to define normal and pathologic values. Okay, so that could be a reason why IgE has not been taken into consideration in myeloma patients…until now, at any rate.
Another interesting finding: IgE is connected to haemoglobin (Hb) and Beta-2 microglobulin (B2M) levels. The researchers found that a high IgE meant a higher Hb and a lower B2M, and this in turn meant a better prognosisl.
In the Discussion part we find the following titbit: The positive association between IgE levels and survival can be interpreted as an indication that (a) the immune system of MM patients with higher IgE levels is less deteriorated […]. Ah.
At any rate, because IgE is an antibody connected to allergy response, the possibility that myeloma patients with allergies such as asthma would be more protected than others in terms of disease progression really (!) got my attention since I suffer periodically from bad attacks of asthma (these attacks have returned, by the way, but I think it’s just because of the change in season from hot to chilly) and other allergic reactions. Hmmm, I thought for a second, have I finally discovered something positive about having asthma and rosacea??? Unfortunately, my hopes were dashed when I read that it is unlikely that allergies play a protective role in myeloma. Bummer!
This study is particularly interesting because for the first time ever a group of researchers has found a connection between IgE levels and survival prognosis. The higher those levels, the better off you are. I wonder if I could have my IgE levels tested…just out of curiosity. Or…on second thought…do I really want to know…???
I’ve always thought that allergies might cause myeloma Margaret.
My reasoning is that if you’ve got something that’s full on all the time, it’s bound to go wrong sooner or later. And what about IL-6. We know that promotes myeloma. I’ve found I suffer a lot less from allergic reactions since I’ve been taking Omega 3 (flax oil). I can even manage tobacco smoke to a certain extent now.
Paul
There is an interesting article at http://myeloma.org/main.jsp?type=article&id=1158 written by an identical twin who developed myeloma whereas her twin did not. The twin who did, received chemotherapy and a marrow transplant from her twin who incidentally had more allergies. After the transplant the twin who received the transplant went into remission and she found that she had developed allergies.
Here’s another article at http://cebp.aacrjournals.org/cgi/content/full/15/12/2342 in which a history of allergy was associated with a decreased risk of myeloma.
Some other studies have found the reverse, however. I would think it might depend on how close in time to MM diagnosis the assessment of allergies was done.
I for example have multiple allergies, and multiple autoimmune diseases, but my MGUS has been identifiable only on immunofixation for years, and my doctor says it has extremely little chance of progressing. I have a feeling that for me at least these autoimmune and allergic signals are a sign that my immune system is actively fighting the aberrant cells.
I’ve just thought of something else. When I studied econometrics, the lecturer used to warn us about shoddy thinking. You should only use statistics to test an hypothesis – not to develop one. In other words, the relationship between allergies and myeloma might be completely different to the one suggested here. For example, the statistics might also support a different hypothesis for myeloma – something I have been thinking about for a while. In this alternative hypothesis, the current staging of MGUS, SMM, MM I), ii), iii), iv), is confusing and irrelevant.
Instead I would have only two types of myeloma:
Primary – the full blown aggressive myeloma we all fear. This is most likely caused by a rogue stem cell, and,
Secondary – or stable myeloma where the paraprotein spike can be stable over long periods of time.
I cannot undertstand how a stable paraprotein fits into the stem cell hypothesis. I would expect some kind of exponential growth in paraprotein levels if the stem cell was dividing continuously . However, if the paraprotein is caused by a chronic reaction to a single antigen, such as an allergy, then maybe this could be why we see monoclonal spikes that stay constant for long periods of time (at least as long as the exposure to the antigen lasts). The allergy might be house dust, wheat, pollen, whatever. As long as your immune system comes up against the same problem, day after day, it will always produce the same response. And since the immune system has a memory, it might take years to recover, even after the allergy has been removed.
Now, if this theory is correct, it could also explain why people with allergies have a better prognosis. It’s simply because they don’t have full blown primary myeloma. However, the allergy in this hypothesis is the villain not the hero.
I am not medically trained so I look forward to someone telling me that my thinking is shoddy.
Best wishes,
Paul
Hi
Interesting line of thought Paul, I have been focusing on my stomach problems and found these interesting articles, which although not linked to myeloma (maybe it should be?) they are studying CFC and depression linked to leaky gut .
http://www.ncbi.nlm.nih.gov/pubmed/18063928?http://www.ncbi.nlm.nih.gov/pubmed/18580840?http://www.ncbi.nlm.nih.gov/pubmed/18063921?(interesting article on fish oils)
what you think Margaret
Hi
Just came up with this study that suggest patients with monoclonal or bicolonal gammopathys should be tested for Bartonella henselae (cat scatch disease) They had a case that was treated and and the gammopathy dissappeared.
http://www.ncbi.nlm.nih.gov/pubmed/12764550?
The name is a bit unfortunate, but relates to gram negative bacteria (see my last comment and links) and are associated with other things, like trench foot.
Here is an except from the link i have added below that looks at this in more detail -: “The fact that Bartonella parasitise erythrocytes without leading to haemolysis, with the exception of B. bacilliformis, suggests that the re-infection waves are due to the liberation of the bacteria from a distant sanctuary site [54]. This unknown primary niche might be the endothelial cells, as suggested by Dehio [54]. However, a number of hints suggest that the primary niche or sanctuary site might instead be located in the bone marrow, as follows. (i) Although, in vitro, Bartonella is able to enter various cells, including macrophages [63], only erythrocytes and endothelial cells are permissive to Bartonella in vivo. The cells that play the role of primary niche should thus share some characteristics common to erythrocytes and endothelial cells. Candidates are mainly the cells that are issued by differentiation of the haemangioblast, the common precursor of both erythrocytes and endothelial cells. These include mainly angioblasts and erythroblasts. (ii) The fact that erythroblasts express VEGF [49], a factor known to enhance Bartonella replication [38]. (iii) All organs involved in bacillary angiomatosis could potentially play the role of sanctuary, including brain, penis, vulva, cervix, muscle and bone marrow [64–68]. However, after skin, bone is the second most frequent site, and bone lesions of bacillary angiomatosis are characterised by well circumscribed osteolysis, that is often painful and usually affects long bones [69]. Pain pattern and osteolysis echo those found in mastocytosis and multiple myeloma, suggesting that bone marrow cells may be infected by Bartonella. (iv) The outstanding features of trench fever are pain and tenderness in the shins and relapsing fever [70]. Many subjects also present only with painful shins, which were often, in the absence of fever, wrongly attributed to flat feet or rheumatism due to prolonged standing in mud and water [70]. This suggests that B. quintana may involve the bone marrow in trench fever patients. (v) The fact that bone marrow cells are highly permissive to Br. melitensis, a phylogenetically close relative of Bartonella spp. and to many other intracellular pathogens. ”
http://jmm.sgmjournals.org/cgi/content/full/51/11/915
Worth asking the doctor about! especially as I had a drop in my paraprotein level teo years ago when i was taking an antibiotic for an unknown skin infection!!
Sue
This is a very interesting site if you are interested in my previous post, (http://home.pon.net/caat/lyme/coinfections1.htm)
below is an extract from a study on this site
“Based on previous studies, a significant percentage of human Bartonella infections have occurred without exposure to known reservoirs or vectors. Up to 30% of human CSD patients may not have been scratched or bitten by cats (33), and 1% of human CSD patients do not have any known contact with animals (35). Although fleas are the main vectors for B. henselae among cats (16), ticks have been suspected to be the source of infection in a few human cases of B. henselae infection (34). An epidemiological study conducted by Zangwill et al. (46) showed that CSD patients were more likely to have found one tick on their bodies than were controls. In a recent outbreak of trench fever in Seattle, Wash., vectors other than lice were suspected in B. quintana transmission because no association was found between body louse infestation and the infection in these human patients (44). In the southeastern United States, two cases of B. quintana-associated central nervous system infection were reported for children with no known history of louse exposure, including one case of rural origin (39). Furthermore, Dermacentor andersoni ticks were identified as competent vectors for B. bacilliformis in an experimental infection of nonhuman primates (37), and a B. bacilliformis-like agent was recently isolated from an I. ricinus tick in Wacz, Poland (31). According to a recent seroepidemiological study of dogs from North Carolina and Virginia, heavy tick infestation was a more important factor associated with B. vinsonii subsp. berkhoffii infection than heavy flea infestation (38). Breitschwerdt et al. further found that dogs infected with tick-transmitted Ehrlichia species are frequently coinfected with B. vinsonii subsp. berkhoffii (8). These findings suggest that ticks could play a role in the transmission of Bartonella organisms.” (http://jcm.asm.org/cgi/content/full/39/4/1221?)
Link for study done to see which antibiotics were effective
http://jac.oxfordjournals.org/cgi/content/full/46/5/811
Sue
Sue, that’s very interesting, considering I have tender shins, and a cat, and have also seen ticks fall off of me in the bathroom.
Paul, your classification is also intriguing.
Good work Sue.
I had painful shins when I was 1st diagnosed but its not a problem any more. We haven’t got any pets now but my hobby is nature photography and I often get bitten by insects. Some take a long time to heal.
How much did your paraprotein drop when you were on antibiotics?
I’ve also been looking into leaky gut syndrome since it could explain a lot too.
Sounds like both of these are potential causes of “secondary myeloma”
Paul
Hi Paul
IgA went from 21 to 19 it was only a short course of antibiotics and 3 months later the levels were back up to 20 it has fluctuated between 20 and 23 ever since (currently at 20.3). It may not be connected but I’m going to ask which antibiotics they were as i can’t remember and compare them too the list used against Bartonella henselae. I certainly feel that the leaky gut issue is worth following and I’m going to ask if I can be referred to have one of these new micro camera pills that are being used to confirm IBS, Crohns, etc
Sue
Sue and Paul, have you considered setting up blogs too? Lots of good info here!
Beth
Hi Beth,
I think it’s best to keep all the info it one place and Margaret does such a great job on research. I’m happy to contribute where I can.
Paul