Farmers’ children had reduced allergen-specific serum IgE levels and their blood leukocytes secreted less inflammatory cytokines in response to bacterial components and expressed more Toll-like receptors. Enhanced TLR expression at birth was associated with a lower risk to develop atopic dermatitis later in life. As an immunological basis for the hygiene hypothesis, several mechanisms have been proposed including a shift in T helper cell type 1/TH2 balance or alteration of dendritic cell, innate immunity and T regulatory cell activities. The innate immunity is the origin of a T helper cell response and the activation of this system is mediated via pathways activated via pattern recognition receptors such as the toll-like receptor signaling cascade or the nucleotide-binding oligomerization domain signaling. To provide proper homeostasis of the innate immune response, a complex regulatory network has evolved. Similarly, cytotoxic and immunosuppressive drugs may suppress immunodefense against malignant cells and lead to oncogenesis. Moreover, there may be a common genetic or environmental susceptibility in autoimmune diseases and plasma cell tumors, or undiagnosed MM may manifest with clinical features that mimic connective tissue diseases. Taking our current results and the above studies into account, the credibility of the antigenic stimulation hypothesis is called into question. Only one cohort study investigated the effect of the duration of follow-up on the risk of MM and determined that the borderline excess of MM was confined to the early 4-year followup. Thomas proposed that although increased risk of MM persisted for hematopoietic cancers throughout the follow-up period, the greatest excess was within the first 3 months after hospitalization. These findings could possibly indicate a common etiologic factor for RA and MM, or further prove the association confirmed in above two studies might be resulted from detection bias. With the current common application of anti-TNF drugs, concern has been raised about the risk of developing malignancy related with their use. However, as implied from two studies mentioned earlier, there was no significant increase in the risk of MM among anti-TNF users. Considering the small number of reports available, further studies are warranted to account for this potential confounder when examining the relationship of autoimmune diseases and MM. Meta-analysis results revealed that pernicious anemia is another risk factor for MM, consistent with several prior epidemiologic studies. Hh, Dpp and N signaling function in initiation and maintenance of the morphogenetic furrow, which sweeps across the field of eye precursors during larval and pupal stages, and separates proliferating from differentiating cells. Although the Hh, Dpp and N signaling pathways regulate expression of genes important for eye development, including Ey, to our knowledge there are no studies that have attempted to identify additional targets, direct or indirect, of these signaling pathways in the context of eye development.