Saori Hatachi

Anti-Programmed Cell Death 1 Antibody Reduces CD4+PD-1+ T Cells and Relieves the Lupus-Like Nephritis of NZB/W F1 Mice

Programmed cell death 1 (PD-1) is an immunosuppressive receptor that transduces an inhibitory signal into activated T cells. Although a single nucleotide polymorphism in the gene for PD-1 is associated with susceptibility to systemic lupus erythematosus, the role of PD-1 in systemic lupus erythematosus is still not well understood. In this study, we used NZB/W F1 mice, a model of lupus-like nephritis, to examine the function of PD-1 and its ligands. PD-1 was predominantly expressed on CD4+ T cells that infiltrated the kidney, and CD4+PD-1high T cells produced higher levels of IFN-γ than CD4+PD-1low or CD4+PD-1− T cells. Stimulation with PMA/ionomycin caused splenic CD4+PD-1+ T cells to secrete high levels of IFN-γ, IL-10, low levels of TNF-α, faint levels of IL-2, IL-21, and no IL-4, IL-17. In vivo anti–PD-1 mAb treatment reduced the number of CD4+PD-1+ T cells in the kidney of NZB/W F1 mice and significantly reduced their mortality rate (p = 0.03). Conversely, blocking PD-L1 using an anti–PD-L1 mAb increased the number of CD4+PD-1+ T cells in the kidney, enhanced serum IFN-γ, IL-10, and IgG2a ds-DNA–Ab levels, accelerated the nephritis, and increased the mortality rate. We conclude that CD4+PD-1high T cells are dysregulated IFN-γ–producing, proinflammatory cells in NZB/W F1 mice.

Reversible posterior leukoencephalopathy syndrome in a patient with Takayasu arteritis

Reversible posterior leukoencephalopathy syndrome (RPLS) has been identified in several connective tissue diseases. However, there are no reports of RPLS associated with Takayasu arteritis (TA). We report the first case of TA associated with RPLS. A 23-year-old woman presented with sudden headache and vomiting, followed by generalized tonic–clonic seizures and mental changes two weeks after administration of oral prednisolone. MRI showed hyperintense signals on T2 and FLAIR images in the bilateral temporal–parietal–occipital lobes, left frontal lobe, and left cerebellar hemisphere. Three weeks after starting control of convulsions and blood pressure with plasmapheresis, high-dose methylprednisolone, and cyclophosphamide, the clinical manifestations and abnormal signals on MRI completely resolved. These reversible clinical and radiological changes are consistent with vasogenic edema in the central nervous system, indicating RPLS. Although high-dose methylprednisolone and cyclophosphamide are thought to cause RPLS, we think that it is justified to use these agents, at least in difficult cases, for making a clear-cut differentiation from CNS vasculitis, as long as blood pressure and fluid volume are well controlled. Moreover, we suggest that RPLS should be included in differential diagnosis of acute neurological changes in connective tissue diseases, including TA.

Presepsin and procalcitonin as biomarkers of systemic bacterial infection in patients with rheumatoid arthritis.

To assess the diagnostic values of presepsin and procalcitonin in patients with rheumatoid arthritis (RA) by identifying those with bacterial infection

CD8+ T-cell lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis during methotrexate therapy

A 75-year-old woman with rheumatoid arthritis (RA) who was receiving methotrexate (MTX) therapy developed Epstein–Barr virus (EBV)-associated CD8+ T-cell lymphoproliferative disorder (LPD) and meningoencephalitis. She was successfully treated with acyclovir and corticosteroids plus MTX cessation. T-cell LPD is relatively rare in RA patients receiving MTX. To our knowledge, this is the first report of CD8+ T-cell LPD with EBV genome occurring during MTX therapy for RA. EBV infection should be carefully monitored to assess severe EBV-associated complications.

Peripheral neuropathies during biologic therapies

Peripheral neuropathies should be recognized as the adverse effects of biological agents, especially anti-TNF agents. However, no solid clinical databases for biological agent-associated peripheral neuropathies (BAPN) have been established in Japan. Here we report two cases of peripheral neuropathy associated with anti-TNF agents. One was peroneal motor neuropathy. The other case was chronic inflammatory demyelinating polyradiculoneuropathy. In addition, we summarize the previous reports on BAPN and discuss their prevalence rate, pathogenesis and management.

Intravascular large B-cell lymphoma with a high titer of proteinase-3-anti-neutrophil cytoplasmic antibody mimicking granulomatosis with polyangiitis

Abstract A 63-year-old man presented with fever, sinusitis, otitis, and high titers of proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA). Granulomatosis with polyangiitis (GPA) was first suspected. However, nasal mucosa and skin biopsies revealed the presence of intravascular large B-cell lymphoma (IVLBCL). We present a rare case of IVLBCL with a high titer of PR3-ANCA mimicking GPA.