Anti-eosinophil peroxidase antibodies detected in patients with primary biliary cirrhosis.

OBJECTIVE:: The possible involvement of eosinophils in primary biliary cirrhosis (PBC) has been suggested for many years. Activated eosinophils release basic granule proteins and are thought to be involved in the tissue damage of PBC. Eosinophil peroxidase (EPO) is one of the eosinophilic granule proteins and is toxic to epithelial cells. In this study, we examined whether autoantibodies to EPO are present in sera of patients with PBC and we evaluated the relationship between the presence of anti-EPO antibodies and the clinical features of PBC. METHODS:: Sera obtained from 61 patients with PBC, 31 patients with autoimmune hepatitis (AIH), 87 patients with chronic viral hepatitis (CVH), 27 patients with bronchial asthma, and 20 healthy controls were examined. Enzyme-linked immunosorbent assay (ELISA) and Western blot methods were used for detection of anti-EPO antibodies. RESULTS:: The mean OD value of anti-EPO antibodies, as determined by ELISA, was significantly (p<0.01) higher in patients with PBC (0.197+/-0.121) than in patients with AIH (0.124+/-0.077), CVH (0.090+/-0.038) or bronchial asthma (0.073+/-0.025) and in healthy controls (0.072+/-0.029). The results of ELISA showed that 32 (52.5%) of the 61 patients with PBC, 9 (29.0%) of the 31 patients with AIH, 7 (8.0%) of the 87 patients with CVH, and 1 (3.7%) of the 27 patients with bronchial asthma were positive for anti-EPO antibodies. In addition, PBC patients who were positive for anti-EPO antibodies had a significantly smaller number of peripheral eosinophils than did patients who were negative for anti-EPO antibodies (99.2+/-54.4cells/mul versus 176.9+/-117.5cells/mul, p<0.01). However, there was no correlation between the titers of anti-EPO antibodies and those of AMA or AMA-M2, ANA or serum levels of IgM. CONCLUSIONS:: This is the first report of the detection of anti-EPO antibodies in patients with PBC. Further study is needed to clarify the role of anti-EPO antibodies in the pathogenesis of PBC.     

A New Ultrasonographic “Fluttering Sign” for Hepatic Hemangioma

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.     

Potential Function of Granulysin,Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9⁺Vδ2⁺ T cells, CD4⁺ T cells and CD8⁺ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry.Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8⁺ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed.Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.     

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014–2015 surveillance studies. Although the rate of detection of extended-spectrum β-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014–2015, the incidence decreased to 8.7% in 2018–2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 μg/mL). By contrast, relatively low geometric mean MICs (0.397 μg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018–2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014–2015, and 38.9% in 2018–2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.     

Characteristics and Prognosis of Colorectal Cancer Associated With Rheumatic Disease

It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression.Key words: Colorectal cancer, Rheumatic disease, Host immunity, PrognosisIt is well known that host immunity plays an important role in defenses against the development and progression of cancer. The degree of lymphocyte infiltration into tumors has been reported to correlate with improvements of patient survival.¹ In carcinogen-induced mouse models of cancer, primary tumor susceptibility has been found to be enhanced in immunocompromised mice; conversely, the capacity for such tumors to grow after transplantation into wild-type mice is reduced.^2,3 Although cancer cells originate from autologous normal tissue, the immune system can recognize even minimal cellular alterations, distinguish cancerous from normal cells, and elicit an immune response.In autoimmune diseases represented by rheumatic disease (RD), the immune system loses the ability to distinguish nonself from self, eliciting an immune response against self-antigens; in this process, there is a possibility that immune defenses against non-normal cells are lost or impaired, facilitating the development and progression of cancer. In addition, the development of RD associated with cancer has been reported, and as its development is dependent on the production of substances such as hormones, peptides, autocrine and paracrine mediators, and antibodies or the stimulation of cytotoxic lymphocytes, the condition is known as paraneoplastic rheumatic syndrome. In such cases, RD tends to be less responsive to therapy than its nonparaneoplastic equivalents, and instead, treatment of the underlying cancer usually results in regression of RD.^4,5 Thus, it is postulated that RD and cancer are closely associated. However, only a few reports on the incidence and risk of cancer among patients with RD exist,^6,7 and the characteristics and prognosis of colorectal cancer (CRC) in these patients remain to be elucidated.In the present study, we investigated the development of CRC in the background of an immunologic disorder caused by RD, with the hypothesis that patients with CRC and autoimmune diseases such as RD will have a poorer prognosis than those without RD, as a result of depressed antitumor immunity caused by immune system incompetence. Thus, we aimed to clarify the features and prognosis of CRC-associated RD, and for this purpose, we compared the clinicopathologic features of patients with CRC with or without underlying RD.