Lupus-Associated Pulmonary Arterial Hypertension: Variable Course and Importance of Prompt Recognition

We describe a critically ill young woman with systemic lupus erythematosus (SLE) presenting with circulatory shock, multiorgan dysfunction, and elevated right-sided heart pressures. She was found to have recurrent acute severe pulmonary arterial hypertension (PAH) in the setting of an SLE flare. Our report highlights the variable course that SLE-associated PAH can take in the same patient and the implications of this for instituting the most effective treatment approach with each episode. This report also highlights the potential for SLE-associated PAH to present with life-threatening symptoms requiring critical care level interventions. We also describe evidence-based therapies, which can result in significant improvement in symptoms, function, and long-term outcomes

Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor

Prostaglandin E(2) (PGE(2)), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE(2) EP2 receptor to cancer-associated immune deficiency using EP2(–/–) mice. EP2(–/–) mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates. While no differences in T cell function were observed, PGE(2) suppressed differentiation of DCs from wild-type bone marrow progenitors, whereas EP2-null cells were refractory to this effect. Stimulation of cells in mixed lymphocyte reactions by wild-type DCs was suppressed by treatment with PGE(2), while EP2(–/–)-derived DCs were resistant to this effect. In vivo, DCs, CD4(+), and CD8(+) T cells were significantly more abundant in draining lymph nodes of tumor-bearing EP2(–/–) mice than in tumor-bearing wild-type mice, and a significant antitumor cytotoxic T lymphocyte response could be observed only in the EP2(–/–) animals. Our data demonstrate an important role for the EP2 receptor in PGE(2)-induced inhibition of DC differentiation and function and the diminished antitumor cellular immune responses in vivo