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A 62-year-old woman with no previous history developed a Capnocytophaga canimorsus infection followed by thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). She was treated with antibiotics and plasma exchange (PE) and recovered. C. canimorsus sepsis sometimes causes not only DIC but also TMA. The mortality of TMA is extremely high, so we should not hesitate to perform PE when a patient shows TMA symptoms.

With expansion of the COVID-19 pandemic, reports of post-COVID-19 interstitial lung disease (ILD) have been emerging. However, there are few reports regarding treatment. Some reports indicate that corticosteroids are effective for post-COVID-19 ILD, but the use of long-term corticosteroid carries risks of side effects. We administered tacrolimus to an elderly patient with post-COVID-19 ILD who suffered a respiratory failure relapse during steroid tapering. The respiratory status improved with tacrolimus in the post-acute phase, but pulmonary fibrosis progressed in the late phase. Tacrolimus may be effective for treating post-COVID-19 ILD in the post-acute phase, but it does not halt progression of pulmonary fibrosis.

A healthy 34-year-old Japanese man presented with a 10-day history of epigastralgia. He had eaten seared chicken sashimi several times. Physical examination findings were not remarkable. Laboratory findings revealed marked eosinophilia (20 ×109/L). Chest CT revealed multiple nodules in the lung surrounded by a halo (figure 1). Abdominal contrast-enhanced CT revealed multiple low-attenuating nodules in the liver (figure 2). An ELISA for Toxocara was strongly positive; thus, a diagnosis of toxocariasis was established. After treatment with albendazole, his symptoms and eosinophilia improved, and the pulmonary and liver lesions disappeared. Figure 1 Chest …

Summary There is increasing interest in the role of T cell exhaustion and it is well known that the natural history of chronic hepatitis C virus infection (HCV) is modulated by CD8+ T cell immunobiology. There are many pathways that alter the presence of exhaustive T cells and, in particular, they are functionally impaired by inhibitory receptors, such as programmed death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). We obtained spleen, liver and peripheral blood (before and after splenectomy) lymphoid cells from 25 patients with HCV-related cirrhosis undergoing liver transplantation for end-stage disease or splenectomy for portal hypertension. In all samples we performed an extensive phenotypic study of exhaustion markers [PD-1, Tim-3, interferon (IFN)-γ) and their ligands (PD-L1, PD-L2, galectin-9] in CD8+ T cell subpopulations (both total and HCV-specific) and in antigen-presenting cells (APC; monocytes and dendritic cells). In the spleen, total and HCV-specific CD8+ T cells demonstrated enhanced markers of exhaustion, predominantly in the effector memory subpopulation. Similarly, splenic APC over-expressed inhibitory receptor ligands when compared to peripheral blood. Finally, when peripheral blood CD8+ T cells were compared before and after splenectomy, markers of exhaustion were reduced in splenic CD8+ T cells and APC. Our data in HCV-related cirrhosis suggest that CD8+ T cells in the spleen manifest a significantly higher exhaustion compared to peripheral blood and may thus contribute to the failure to control HCV. Counteracting this process may contribute to inducing an effective immune response to HCV.

Stenotrophomonas maltophilia is an important nosocomial bacterial pathogen, as is Pseudomonas aeruginosa. Differentiation of these bacteria as bacteremic agents is critical in the clinical setting and to define a therapeutic strategy; however, the associated factors and prognosis for S. maltophilia bacteremia have not been fully evaluated to adequately characterize these factors. We first conducted a matched case-control study to clarify these questions. A total of 30 case patients with S. maltophilia bacteremia were compared with 30 control patients with P. aeruginosa bacteremia between January 2005 and August 2014, according to matching criteria based on underlying disease, age, and gender. The 30-day mortality rate for the case patients (53.3%) was significantly higher than that of the control group (30.0%) (P = 0.047, using the log-rank test). Conditional logistic regression analysis showed that the predisposing factors specific for the detection of S. maltophilia bacteremia were indwelling artificial products other than a central venous catheter, ICU stay, and previous use of anti-MRSA drugs. The high severity of illness was associated with mortality in both case and control patients. Interestingly, inappropriate antimicrobial treatment was an additional independent risk factor for mortality in only the case patients with S. maltophilia bacteremia (odds ratio = 13.64, P = 0.048). Monotherapy with fluoroquinolones inactive against the S. maltophilia isolates was mainly responsible for the inappropriate treatment. These results suggest that more precise prediction and more appropriate treatment might improve the prognosis of patients with S. maltophilia bacteremia.

Aim. We analyzed the pretreatment natural killer (NK) cell functions with the aim of predicting the sustained virological response (SVR) or the interleukin (IL) 28B polymorphism that is strongly associated with the treatment response. Methods. The peripheral NK cells from chronic hepatitis patients with HCV genotype 1 and high virus titers were activated using a Toll-like receptor (TLR) 4 ligand and IFN-α. The cell surface markers were evaluated using a flow cytometric analysis, and IFN-γ production was evaluated using an enzyme-linked immunosorbent assay (ELISA). The genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on the DNA collected from each patient. Results. The production of IFN-γ was significantly higher in the SVR patients compared with the no-response (NR) patients, whereas the cell surface markers were similar between the SVR and the NR patients. There were no significant differences found in the IL28B genotype distribution associated with the production of IFN-γ. Conclusion. Differences in the NK cell functions were observed between the SVR patients and the NR patients, suggesting that NK cells play a potential role in the treatment response independent of the IL28B genotype.

Primary biliary cirrhosis (PBC) is a female-predominant organ-specific autoimmune disease characterized by destruction of intrahepatic small bile duct biliary epithelial cells (BECs) (1). The serological hallmark of PBC is the presence of anti-mitochondrial auto-antibodies (AMA) directed against the pyruvate dehydrogenase E2 complex (PDC-E2) located in the inner membrane of mitochondria (2–4). High frequency of CD4+ and CD8+ T cell infiltrates have been noted within the portal tracts of PBC liver, which strongly suggests that these cells are involved in the pathogenesis of PBC (5). Indeed PDC-E2 specific autoreactive CD4+ T and CD8+ T cells have been identified both in peripheral blood and, at much higher levels, in liver of PBC patients (6–8). The dominant CD4+ and CD8+ T cell epitopes on PDC-E2 has been mapped (6–8). While both CD4+ and CD8+ T cells are present within portal tract infiltrates, there is a growing body of data that suggests a more direct role of cytotoxic CD8+ T cells in biliary destruction (9–11). The study of effector pathways is a particularly challenging problem in human autoimmunity. For one thing, the majority of effector pathways are likely to be mediated by non-specific bystander cells recruited during inflammation. For another, it has been difficult to identify subpopulations of cells by phenotype and thence link such data to functionality. Our laboratory has focused attention on effector T cell populations using a variety of technologies and has highlighted the important role of T cells in this and similar pathways. In this study we took advantage of newer reagents including cell surface markers that are associated with CD8high effector memory T cells (TEM), organ and tissue specific homing and alterations in susceptibility to apoptosis. Indeed, we report that patients with PBC not only have an increased frequency of CD45ROhighCD57+CD8high T cells compared to controls, but also that such cells have increased α4β7 expression with concurrently increased expression of CCR5 and decreased expression of CCR7 and CD28 compared to other CD8high T cells. Further, this T cell subset has increased production of granzyme A, granzyme B and perforin compared with other CD8high T cells and interestingly have decreased stimulation-induced apoptosis. Furthermore, IFN-γ and IL-5 produced by CD8+CD57+ T lymphocytes upon in vitro TCR stimulation are increased in PBC patients. Histologically, CD8+CD57+ T cells accumulate around the portal area in the liver of PBC patients. Moreover, purified CD8+CD57+ T cells from PBC patients specifically respond to the MHC class I restricted epitope of PDC-E2. These data have implications for understanding CD8 effector pathways in this autoimmune disease. We submit that CD45ROhighCD57+CD8high T cells are a subset of cytotoxic memory cells which play a critical role in the chronic and progressive destruction of BECs in PBC.