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In mice, the two distinct autosomal recessive genes lpr and gid can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8-T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4 -CD8 -T cell population. These CD4 -CD8 -T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the a /If form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gid mice. (J. Clin. Invest. 1992.90:334-341.)

ObjectiveTo compare the relative bioavailability, safety and tolerability of oral methotrexate (MTX) and subcutaneous (SC) MTX administered via an auto-injector (MTXAI) in patients with rheumatoid arthritis (RA).MethodsIn this randomised, multicenter, open-label, three-way crossover study, patients ≥18 years with adult RA undergoing treatment with MTX for ≥3 months were assigned to receive MTX 10, 15, 20 and 25 mg weekly in a random sequence of three treatments: oral, SC into the abdomen and SC into the thigh. For 24 h after administration of each treatment, blood samples were collected for pharmacokinetic analysis and injection sites were assessed.ResultsForty-seven patients completed the study. Systemic exposure of oral MTX plateaued at doses ≥15 mg/week. In contrast, SC MTX demonstrated a linear increase in systemic exposure that was greater than oral MTX at each dose. No unexpected AEs were noted for either formulation.ConclusionsUnlike oral MTX, the systemic exposure of SC MTX did not plateau over the doses studied, particularly at doses ≥15 mg/week. In this study, higher systemic MTX exposure was not associated with increases in AEs. Patients with an inadequate clinical response to oral MTX may benefit from higher drug exposure by switching to SC MTX.Trial registration numberNCT01618968.

In de novo renal-transplant recipients, the regimen of everolimus plus RDN was well tolerated, with low efficacy failure and better renal function in comparison with everolimus plus FDN.

No abstract

This study indicates that for renal transplant patients in whom RAPA treatment induces hyperlipidemia, this effect is the result of reduced catabolism of apoB100-containing lipoproteins.

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Clinically, the pharmacological effect of CSA is quantifiable, and lies in the upper end of the predicted range. In our Neoral-treated sample population, Cmax was associated with the least variable "cyclosporine effect." Such information could potentially individualize immunosuppression, and lead to rational dosing strategies.