Transcription factors and corresponding cis-regulatory elements are considered key components in gene regulation. We combined biostatistics and bioinformatics tools to streamline identification of putative transcription factor-gene regulatory networks unique for two immune-mediated diseases, ankylosing spondylitis and sarcoidosis. After identifying differentially expressed genes from microarrays, we employed tightCluster to find tight clusters of potentially co-regulated genes. By subsequently applying bioinformatics tools to search for common cis-regulatory elements, putative transcription factor-gene regulatory networks were found. Recognition of these networks by applying this methodology could pave the way for new insights into disease pathogenesis.