Jasper9 wrote:I had the balloon treatment in Edinburgh last month - no major changes yet but it's still early days and my symptoms are relatively mild.
According to the so-called hygiene hypothesis , modern living conditions in the industrialised nations isolate infants and children from many infectious challenges that are required for the development of appropriate immunoregulatory networks. This hypothesis has been advanced to explain the rise in incidence of disease associated with immune dysregulation, including asthma, allergy, autoimmunity and at least some forms of cancer, in the industrially developed world . In addition, the hypothesis suggests strategies for interventions for the prevention of such diseases, as illustrated by studies on the epidemiology of malignant melanoma which indicate that certain vaccinations, BCG, vaccinia and yellow fever, can substitute for the significant protective effect of natural infections [8–11]. As epidemiological investigations on MS strongly indicate that this disease is likewise affected by hygiene-related factors and by a history of infections [3, 6], the challenge is to determine whether there is an underlying distortion of immune responses in this complex disease that could be prevented or corrected by therapeutic intervention.
The temporal sequence of infections, especially initial and early ones, is crucial to the development of patterns of immune reactivity as prior contacts with other antigens may have induced cross-reactive T-helper cells competing with Tregs. As a consequence Tregs normally induced by the second pathogen may be marginalized or even eclipsed. The latter phenomenon, also known as lateral inhibition, has many parallels in biology, particularly in neurology. The locking of an immune response into an eclipsed state seems to involve an active deletion of clones of T-cells occurring as a result of reinfections or reactivations . In the case of MS, infections such as those with HHV-6 [30, 31] and, possibly, with CP [12, 26] occurring before or at the time of initial or reactivated EBV infection could have such an effect.
Jasper9 wrote:But it's the science behind it (antigens, cytokines, FOXP3.....) that I'm finding hard to understand, and whether this science ties in at all with the science of HSCT.
During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients. Furthermore, myelin basic protein-specific responses in peripheral blood showed a significant increase in IL-10 and TGF-beta and a decrease in IL-12 and interferon-gamma-secreting cells in infected MS patients compared with noninfected patients. Myelin basic protein-specific T cells cloned from infected subjects were characterized by the absence of IL-2 and IL-4 production, but high IL-10 and/or TGF-beta secretion, showing a cytokine profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of CD4+CD25+ FoxP3+ T cells was substantially increased in infected patients compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not detected in T cells from infected MS patients secreting TGF-beta.
Among the various autoimmune diseases, multiple sclerosis has been the main indication for autologous HSCT. A recent review summarized the data on 400 patients in 12 trials. Patients had either remitting-relapsing or primary progressive disease and conventional immunosuppression had failed. Disease stabilization and improvement occurred in around 70% at least up to 3 years after transplantation. The timing of HSCT in multiple sclerosis may be critical as there is growing evidence that at some stage of the disease neurodegeneration may progress independently of autoreactive processes.
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