One hears statements of this kind while playing the popular board game “Clue.” Players of Clue must travel around an imaginary old mansion while collecting hints. Based on hints, players make educated guesses about the “where, who, and with what weapon” facts of a murder mystery.
Pursuing better treatments and cures for Systemic Lupus Erythematosus (SLE) is a little like playing an exceedingly complicated game of Clue. Villainous SLE has done dastardly deeds, reducing quality and quantity of life for many of its victims. Researchers who would bring SLE to justice confront a daunting array of “weapons” (infections, hormones, drugs, lifestyle choices, host immune cells run amok) that could inflict injury within the “mansion” of a patient’s immune system. Like Clue players, researchers must use logic. As in Clue, they must also test proposals (called hypotheses, frequently based on observations in patients) with experiments in the laboratory. They must spend long months and years testing these proposals to track causes of SLE to their sources.
Fortunately, investigators hunting the causes of SLE in the past decade have been equipped with more powerful tools than a few dice and Clue game cards. In particular, researchers at the University of Minnesota, including Drs. Timothy Behrens and Emily Gillespie, made use of a powerful technique called gene expression profiling. The technique allows simultaneous analysis of the behavior of thousands of white blood cell genes in SLE patients. Nearly 10 years ago, these investigators were among the first to report that the majority of SLE patients show a distinctive pattern of blood gene expression (Baechler et al, Proceedings of the National Academy of Sciences, 2003). They dubbed the pattern the Type 1 Interferon “signature” because numerous active genes in the SLE-associated blood profile are controlled by a powerful natural chemical called type 1 Interferon. After observing the signature, they proposed that uncontrolled type 1 Interferon might serve as a major instigator of tissue damage in SLE.
In the ensuing 10 years, Drs. Behrens and Gillespie and many other researchers have been working to establish a cause-and-effect relationship between type 1 Interferon and tissue injury in SLE. Their follow-up work has resulted in numerous insights about the cells that produce type 1 Interferon and how those cells are excited by stimuli such as infection.