シェーグレン症候群に対する病期対応型テーラーメード医療の構築

Sjögren's syndrome (SS) is one of the most common rheumatic diseases. Histopathologic features of SS salivary glands include: (a) the eventual total replacement of the acinar structure by marked lymphocytic infiltrate and (b) the occurrence of various changes in the ductal structure within infiltrated areas, such as metaplasia, hyperplasia, thinning of ductal layer, or oncocytic change, and in some cases the formation of epimyoepithelial islands arising from ductal proliferation. Accordingly, surviving and/or proliferating ductal cells in SS salivary glands may be regarded as one of the possible sources for the improvement of salivary secretion. Thus far, I found that inhibition of TNF-α-induced MMP-9 production in acinar cells lead to restored integrity of the acinar structure in SS salivary glands. Therefore, in this review I would like to postulate a tailor-made therapy based on the diseasestage of SS. First, therapy for the inhibition of lymphocytic infiltrate into salivary glands by regulating balance of sex hormones in acinar cells (early stage of SS); second, therapy for the maintenance of stable acinar structure by inhibiting cytokine-induced basement membrane-degrading enzymes, such as MMP-9 (intermediate stage of SS); and third, therapy for the bestowal of ability to secrete saliva on ductal cells (late stage of SS). Hopefully, these disease stage-specific therapies would contribute to the improvement of QOL of SS patients.