Jonathan Edwards
"Gibberish"
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Prof. Edwards, earlier in the thread you said that the reason that IVIG is used is not to replenish IgG levels, but to replace the patient's IgG with a healthy person's IgG. I don't fully understand what you mean by this. IVIG was used in those Ritux patients with Hypogammaglobulinaemia - this would seem to be replenishing, since the aim is to get the patient's IgG levels to where they were before they were treated.
I also find it difficult to understand how diminished IgM and IgA levels are not important. I can sort of see why IgM might not be important, if the body is still able to produce IgM in response to a new infection (the question then is whether the B-cell depletion would significantly reduce this), but surely IgA is important, since this is the major immunoglobulin in the gut, and diminished levels would have an immediate impact on the immune system's regulation of the gut, wouldn't they?
IVIG is given for ME as a primary treatment, presumably tried because IVIG seems to help certain autoimmune conditions like immune thrombocytopenia and dermatomyositis. Nobody knows the mechanism in any of the autoimmune diseases it has been used for and nobody really knows if it works much, except perhaps for immune thrombocytopenia. Since the patients given IVIG in this context have normal Ig levels then the treatment is not a replenishing one. It seems that it has to be something to do with other people's Ig being better for the patient than their own - or maybe mopping up the patient's bad Ig. It will not depress Ig production much because the feedback mechanism does not seem to be through Ig itself (again nobody really understands this).
After rituximab the reason for giving IVIG is completely different. It is not a treatment for the ME, but simply a way of keeping up antibody immunity to common infections. It is not a matter of getting back to what it was before so much as getting up to a baseline immune level - about 6gm/L or so.
All that one can say about IgA and IgM levels is that they do not seem to matter much in practice. Genetically determined IgA deficiency is very common in the general population and does not seem to matter on its own. The reason for thinking that low IgM does not matter much is that it often falls after rituximab but without any associated problems.
It might seem as if these antibodies are terribly important to immunity and health but it is worth remembering that there are reasons to think this is too simple. When you meet an potentially serious infection in almost all cases you will fight off the infection within two weeks - or at least get it under control. Antibody production has hardly started by then. So making new antibodies probably has rather little to do with fighting off infections in the normal situation. In fact people with no antibodies (Bruton's kinase deficiency or agammaglobulinemia) manage reasonably well a lot of the time. Eventually they run into chronic infection problems but that may have quite a bit to do with not having antibodies to help antigen presentation to T cells (i.e. presentation by B cells).
One way of looking at antibodies is that they are really mostly for newborn babies, for priming responses by other cells and for pre-emptively knocking out infections a second time around. Newborn babies need antibody to prime their systems so that they can develop T cell immunity to all the common pathogens. They have to get it from mother through the placenta. Once things are primed you can run pretty well on macrophages and T cells and some old stock antibody you have from long lived plasma cells.
Things are clearly not quite as simple as that because there probably is an increased risk of infection if you develop secondary hypogammaglobulinemia after rituximab. However, the vast proportion of problems occur in cases where there are other reasons for low resistance, like lymphoma and multiple chemotherapy.