Antigen-Specific Immunotherapy to Treat Autoimmune Disease
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Autoimmunity as a term covers a broad range of ways in which the immune system can run awry to attack healthy tissues. It bears some semblance to cancer in that an autoimmune disorder can occur at any age, there are many, many different types, and the details of the biochemistry involved are enormously complex and comparatively poorly understood. There is no good consensus on why some of the most common autoimmune diseases such as rheumatoid arthritis occur, for example, and the most successful of presently available treatments focus on suppressing the activities of the malfunctioning immune system in as targeted a way as possible rather than addressing the root causes of that malfunction - as the root causes are not yet well enough categorized to identify a point of action. A number of named autoimmune disorders are diagnoses of exclusion: you have the condition because you show some of a grab bag of unpleasant symptoms yet all of the tests for other named autoimmune conditions come back negative. There tend to be no reliable treatments in those cases.

Some autoimmune diseases are not age-related at all, but others are, beyond the assurance of "live long enough and something will go wrong," that is. Certainly the immune system as a whole deteriorates and malfunctions in other characteristic ways with advancing age, becoming increasingly ineffective yet constantly active to generating increased and harmful levels of chronic inflammation. Some researchers have made inroads in a fairly drastic approach to treating autoimmunity: wipe out the entire immune system with chemotherapy and repopulate it with immune cells derived from the patient's own stem cells. This has proven effective in a number of trials for more serious, life-threatening autoimmune conditions, and was even tried for rheumatoid arthritis some years ago before the advent of TNF inhibitors and other immune suppression treatments. The medical community embraced the less drastic approach of partially effective medical control over the more drastic approach of a sometimes cure, however. I suspect the chemotherapy would have to be replaced with a kinder, gentler, and less risky process of stripping the immune system for that approach to gather more funding and attention, or even be considered as a way to reset an age-damaged immune system.

Here is recent news from researchers working on an interesting alternative approach to treating autoimmunity. This has been under investigation for some time, and involves a process of steadily desensitizing key immune cells, training them not to react to certain proteins known to be involved in the autoimmune response. While full details of causation remain to be determined for many autoimmune disorders, researchers do have lists of protein targets to work with in this way in some cases. Note that the paper is open access if you want to delve further:

Scientists discover how to 'switch off' autoimmune diseases

Rather than the body's immune system destroying its own tissue by mistake, researchers have discovered how cells convert from being aggressive to actually protecting against disease. It's hoped this latest insight will lead to the widespread use of antigen-specific immunotherapy as a treatment for many autoimmune disorders, including multiple sclerosis (MS), type 1 diabetes, Graves' disease and systemic lupus erythematosus (SLE).

Scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body's own tissues while converting them into cells capable of protecting against disease. This type of conversion has been previously applied to allergies, known as 'allergic desensitisation', but its application to autoimmune diseases has only been appreciated recently. The group has now revealed how the administration of fragments of the proteins that are normally the target for attack leads to correction of the autoimmune response. Most importantly, their work reveals that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.

Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy

While progress has been made in developing disease-modifying therapies for the treatment of autoimmunity, it is increasingly clear that successful therapy will need to reinstate long-lasting immunological tolerance to the targeted self-antigens, thereby preventing pathogenic ​CD4+ T-cell responses. This must be achieved without perturbation of normal immune function, leaving anti-microbial and tumour immunosurveillance responses intact. Antigen-specific immunotherapy aims to fulfil these requirements: administration of disease-associated ​CD4+ T-cell epitopes in a tolerogenic form has been shown to restore immune homeostasis and prevent immunopathology in experimental models, as well as in clinical trials of both autoimmune diseases and allergies.

We have developed a dose escalation strategy for efficient self-antigen-specific tolerance induction and characterized sequential modulation of ​CD4+ T-cell phenotype at each consecutive stage of escalating dose immunotherapy (EDI). We show that self-antigen-specific tolerance can be effectively induced via the subcutaneous (s.c.) route. We demonstrate that antigen dose plays a critical role in determining the efficacy of immunotherapy, and that a dose escalation protocol is imperative to allow safe s.c. administration of the high antigenic doses required for efficient tolerance induction. We reveal that EDI minimizes ​CD4+ T-cell activation and proliferation during the early stages of immunotherapy, preventing excessive systemic cytokine release.


As someone who has an anti nuclear antibody blood level of 2560 (normal is 60!) I find this post very interesting.

Posted by: Jim at September 11, 2014 11:09 PM
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