To preserve residual beta cell function we have intervened in patients with recent onset of Typ 1 diabetes by giving GAD ( Glutamic Acid Decarboxylase) -alum sc , which gave some interesting results, Last years we have tried giving GAD-alum directly into lymphn-node and see a very pronounced, different immune response . I would be very interested in hearing YOUR opinion, both from people working with diabetes immunology, but also from you working within other fields like reumatology, MS, oncology etc. Thanks for your answers.
Dear Prof.Ludvigsson,
As we know, antijene must get from sites of entry to lymphatic system and be presented to the lymphocytes there. This happens mostly by 2 ways, it can drain to lymphatic system by passive means or may be actively transported by specialised cells such as dendritic cells. These cells are present in lymph nodes and other tissues( but in less amount). The langerhans cells in the skin are a type of dendritic cells. This more dendritic cells in the lymph nodes may lead to easy and more presentation of GAD antigens to the lymphocytes and thereby initiation of immune response. This is my explanation to better response of GAD vaccination into lymph nodes in your study. If the results of this method is promising, we may inject the vaccine to skin nearby the lymph nodes..( special method?)'
Dear Mehmet Hursitoglu,
Thanks for this reply. But if it is just a question of more presentation, why don´t we just get a stronger respons, but of the same type as after sc administration?
As I said, dendritic cells are more prominent in the lymphatic system than the skin. In lymphatic cells dendritic cells present it directly to T cells ..This is my explanation. What would be your explanation?
Could you please elaborate: what is the difference in the immune response you are seeing when administered sc or directly into lympnode (which lymph nodes?)? Is one immune response more regulatory (IL-10, TGF-beta, etc.) and the other more pro-inflammatory (IFN-gamma, IL-17A, etc.)? Without some additional information it will be difficult to answer your question.
Actually I would have liked your principal view, what is to be expected, and not only a comment on what we have seen. But OK: After sc administration we see a transient Th2deviation with some increase in especally IL13, IL-10 , decreaaw i IFNgamma, IL17, and GADA IgG1 decreases after 3 months but then increases again. After Lymphnode administration there is a much more pronounced Th2 deviation, with massive production of IL13, proportionally very pronounced decrease of IFNgamma, IL17...- GADA IgG1 decreases very much, while IgG2,3,4 increase. AFter 15 months we see a gradual increase in IL10, TGFbeta..
Best wishes
Johnny
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