Infections and the relationship to treatment in neuromuscular autoimmunity.

INTRODUCTION: This study aimed to identify infections in patients with myasthenia gravis, dermatomyositis, and chronic inflammatory demyelinating polyradiculoneuropathy, and to investigate the relationship between infection and immunomodulation. METHODS: A retrospective chart review examined 631 patients with myasthenia gravis (n = 358), chronic inflammatory demyelinating polyradiculoneuropathy (n = 124), and dermatomyositis (n = 149) patients over a 10-year time period. RESULTS: Infection rates were similar at approximately 19% in all 3 diseases. Of the infections in which a causative organism was identified, pneumonia, sepsis, and opportunistic infections were the leading diagnoses. A multivariate model demonstrated a significant association between infection and an increased dose of plasma exchange, mycophenolate mofetil, and corticosteroid therapy. DISCUSSION: There are few large studies investigating rates of infections in patients with autoimmune neuromuscular disorders and the relationship to immunomodulation. This study not only demonstrates the remarkably similar infection rates across the 3 diseases studied, but also shows their relationship to commonly used immunotherapies. Muscle Nerve 57: 927-931, 2018.

Transcription factor ATF3 links host adaptive response to breast cancer metastasis.

Host response to cancer signals has emerged as a key factor in cancer development; however, the underlying molecular mechanism is not well understood. In this report, we demonstrate that activating transcription factor 3 (ATF3), a hub of the cellular adaptive response network, plays an important role in host cells to enhance breast cancer metastasis. Immunohistochemical analysis of patient tumor samples revealed that expression of ATF3 in stromal mononuclear cells, but not cancer epithelial cells, is correlated with worse clinical outcomes and is an independent predictor for breast cancer death. This finding was corroborated by data from mouse models showing less efficient breast cancer metastasis in Atf3-deficient mice than in WT mice. Further, mice with myeloid cell-selective KO of Atf3 showed fewer lung metastases, indicating that host ATF3 facilitates metastasis, at least in part, by its function in macrophage/myeloid cells. Gene profiling analyses of macrophages from mouse tumors identified an ATF3-regulated gene signature that could distinguish human tumor stroma from distant stroma and could predict clinical outcomes, lending credence to our mouse models. In conclusion, we identified ATF3 as a regulator in myeloid cells that enhances breast cancer metastasis and has predictive value for clinical outcomes.