**6.3. Auto-immune diseases**

In response to many pathological processes, the humoral immune system generates antibodies to self-proteins ("auto-antibodies"). These auto-antibodies are generated due to antigen over-expression, mutation, altered post-transcriptional modifications of altered degradation released from damaged tissue which lead to their recognition by the immune system. Autoantibodies have several benefits which make them as suitable source of biomarkers: (1) They have been discovered before the appearance of clinical symptoms; (2) They are simple to identify even at low levels once their target antigen is known; (3) they are easy to reunite from blood; and (4) they could be show in higher levels and with a longer half-life than their target antigens, which may only be present in transiently in blood [10].

For example, NAPPA arrays were used for serological screening for the first time in 2007 by- Anderson et al. They investigated the presence of antibodies against tumor antigens in breast cancer. The tumor-suppressor p53 is well-characterized in several solid tumors and the presence of antibodies against p53 is mainly due to mutations in its gene which lead to alterations- in its half-life. By this approach, the authors presented that p53-specific antibody levels were- significantly lower in healthy donors than in breast cancer patients and the response to p53 antigen was detected in Stage II disease. Also they studied that the antigen sites of p53 with several- antibodies which recognized distinct epitopes of the protein to confirm that many regions of the- protein expressed in NAPPA were accessible to antibodies in serum detected to them [10, 30].

In a follow-up work, also this group performed a wide screen for new auto-antibodies in breast cancer. They designed and developed 4988 candidate antigens to detect their auto-antibodies in serum samples from breast cancer patients with stage I–III disease. This screening was performed in three stage design that entailed comparing cases and controls and eliminating uninformative antigens at each stage. At the final phase, slightly more than 100 antigens were tested and 28 auto-antibodies were identified that distinguished benign breast disease from invasive cancer under blinded conditions [10, 30].

With a similar workflow, Labaer etal. developed a pilot NAPPA to assess auto-antibodies present in juvenile idiopathic arthritis (JIA) which is a disease characterized by chronic joint inflammation in children [31].

Recently, Fuentes's lab has performed a screening of auto-antibodies in osteoarthritis and arthritis rheumatoid by using NAPPA arrays and validated with other protein arrays technologies [32].
