Antibody microarrays consist of antibody probes and antigen targets; thus, they can be used to measure concentrations of antigens for which the antibody probes are specific [65, 66] . As such, antibody microarrays are quite useful in proteomic applications, such as in the proteomic profiling of cancer antigens [67] [68] [69] . Antibody microarrays have also been proposed for post-translational functional genomics [70] . The rationale for directly measuring protein concentration, rather than using a traditional DNA microarray format, is the existence of evidence of poor correlation between concentrations of mRNA and its corresponding protein, which reflects post-translational modification of the protein [71] . Given the possibility of measuring antigens or proteins associated with ''foreign agents,'' antibody microarrays can be employed in functional immunomics applications [72, 73] (The application in [73] actually used cells, which display the target protein markers on their surfaces.) As a general rule, however, using antibody microarrays in data-driven functional immunomic applications may be problematic. One of the main reasons is that this approach requires the production of specific antibody sets for use in defining each of the antigen targets, and the development of large numbers of interrogative features (antibody sets) is a tremendous challenge, since humoral responses are much broader than MHC-restricted T cell responses, are highly conformationally dependent, and can be developed against a great variety of chemical/biological elements present in biological fluids, including small molecules. Peptide microarrays use the opposite technical approach; that is, they use antigen peptides as fixed probes and serum antibodies as targets [74] . This format is promising for functional immunomic applications. Published studies using peptide microarrays include applications to autoimmune disease [10, [75] [76] [77] [78] [79] , allergy [80] [81] [82] [83] [84] [85] , B cell epitope mapping [13, [86] [87] [88] , vaccine studies [89, 90] , detection assays [91, 92] , serum diagnostics [12] , characterization of weak protein interactions [93] , and analysis of antibody specificity [94] . Peptide microarrays essentially correspond to highthroughput parallelized ELISA assays [12, [95] [96] [97] [98] and thus can reveal the repertoire status of antigen-specific B cell antibody responses. However, B cell responses are highly dependent on CD4 þ T cell immune responses, and thus peptide microarrays should ideally be used in parallel with extensive analysis of T cell responses (e.g., by using peptide-MHC microarrays; see below). One of the pioneer studies that best depict the usefulness of peptide immunomic technology was performed using an array of 87 protein antigens to search for specific antibody reactivity patterns in the serum of 20 normal health volunteers; these were compared to the patterns of 20 type-1 diabetes mellitus patients, and simple classifiers were designed to discriminate between healthy and diabetic patients, with an overall sensitivity of 95% and specificity of 90% [78] . In a subsequent study, the 87-feature array was able to identify prognostic signatures that could predict the susceptibility of healthy animals to develop diabetes [10] . Another important report describes the use of a panel of 225 selected peptides of several protein antigens known to be recognized by autoimmune disease patients [79] . The autoimmune peptide array was used to study the profile of the autoantibody reactivity pattern of rheumatoid arthritis (RA) patients. The RA study used serum from 18 RA patients, 38 healthy controls, and 58 recently diagnosed RA patients, and found early clinical prognostic markers able to predict which patients are more likely to develop severe RA, and also markers to identify the group of patients with the milder form of the disease [77] . Moreover, an array developed from a panel of 213 peptides derived from allergenic peanut proteins established that patients responding to a greater diversity of peptide peanut epitopes had the worst allergic reactions [80] . The importance of the breadth of antibody response against the simian-human immunodeficiency virus (SHIV), a experimental nonhuman primate model for human immunodeficiency virus (HIV), was demonstrated through studies performed with an array of 430 peptides derived from simian immunodeficiency virus (SIV) and HIV amino acid sequences [90] . This study indicated that the reduction of the repertoire of the antibody response was associated with development of acquired immunodeficiency syndrome (AIDS). These examples underscore the great potential of peptide microarrays to identify several valuable clinical markers.