Similar to severe patient with Class II mutation, pathways involved in inflammation and immune response were also defined in severe patient with Class IV mutation. But advanced glycation end products and receptor of advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications (p=7.24E-06) and TLR signaling pathway (p=0.0001) were found to be specific to Class IV group. Possible molecular mechanism was summarized in Figure 3.