sirolimus and Dermatomyositis

Peripheral blood T lymphocytopenia has previously been identified in polymyositis/dermatomyositis (PM/DM) patients. Therefore, the present study aimed to examine the potential role of autophagy in peripheral blood T cell survival in PM/DM patients. Transmission electron microscopy was used to detect the formation of autophagosomes of peripheral blood cluster of differentiation (CD)3+ T cells obtained from 24 patients with PM/DM and 21 healthy controls. Protein and mRNA expression levels of autophagy‑related molecules were examined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction, respectively. The number of peripheral blood CD3+ T cells decreased significantly in PM/DM patients. The median percentage of apoptosis of CD3+ T cells in PM/DM patients was significantly increased compared with healthy controls. Furthermore, the number of autophagosomes and the expression of the autophagy markers microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Beclin‑1 were significantly reduced in the circulating CD3+ T cells of PM/DM patients compared with those of healthy controls. LC3 and Beclin‑1 protein levels correlated negatively with apoptosis rates in circulating CD3+ T cells in patients with PM/DM. CD3+ T cells from PM/DM patients treated with rapamycin increased autophagy and decreased apoptosis compared with untreated cells (P<0.05). In conclusion, these results suggested that autophagy may serve a potential protective role in the peripheral blood T cells of patients with PM/DM.

Topics: Adult; Aged; Apoptosis; Autophagy; Case-Control Studies; CD3 Complex; Cell Separation; Cell Survival; Dermatomyositis; Female; Humans; Lymphocyte Subsets; Male; Middle Aged; Polymyositis; Sirolimus; T-Lymphocytes; Young Adult

Posttransplant lymphoproliferative disorder (PTLD) remains one of the most important complications of intensive immunosuppressive therapy. A 65-year-old Caucasian woman received a primary en bloc kidney transplant from a deceased 2-year-old donor. After antithymocyte globulin induction she was treated with a maintenance regimen including cyclosporine and mycophenylate mofetil (MMF). She had a history of recurrent dermatomyositis, suggesting a flawed immune system. After a benign course for 9 months and after an increase in MMF from 2 to 3 g daily, she presented with pneumonia owing to Candida albicans, which was responsive to antibiotics, as was the PTLD. Persistent fever led to a diagnosis of PTLD. The immunosuppressive regimen was converted to sirolimus (SRL) and rituximab, with over 90% necrosis of the neoplasm at 1 month. However, owing to concern at exploration, the allografts were extirpated. This case documented the benefit of the rituximab-SRL combination to treat PTLD while maintaining dermatomyositis in remission.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Appendectomy; Child, Preschool; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Kidney Function Tests; Kidney Transplantation; Lymphoproliferative Disorders; Ovariectomy; Postoperative Complications; Rituximab; Sirolimus

Dermatomyositis is an autoimmune condition that results in significant morbidity and mortality through effects on muscle and skin. Corticosteroids are the mainstay of therapy of dermatomyositis, and severe morbidity and mortality occurs in part through the known long-term side effects of chronic steroid use. In addition, dermatomyositis is commonly associated with underlying malignancy, and high-dose steroids may adversely impair treatment of these malignancies. We describe the first use of rapamycin in a young patient with dermatomyositis.

Topics: Adult; Autoimmune Diseases; Dermatomyositis; Female; Glucocorticoids; Humans; Hypertriglyceridemia; Immunosuppressive Agents; Prednisone; Sirolimus