Anti-type II collagen antibody accelerates arthritis via CXCR2-expressing cells in IL-1 receptor antagonist-deficient mice

Arthritis can be induced in mice by the injection of anti-type II collagen (anti-CII) Ab and LPS. To elucidate the role of IL-1 receptor antagonist (IL-1ra) in Ab-induced arthritis, WT and IL-1ra(-/-) mice were administered anti-CII Ab and LPS. These IL-1ra(-/-) mice developed severe arthritis even at low doses of anti-CII Ab and LPS, while WT mice did not. The cells that invaded the arthritic joints were mainly Gr-1(+) neutrophils, and the number of the cells in the joints remained high over 4 weeks in the IL-1ra(-/-) mice. KC, a ligand for CXCR2, is found in higher levels in the arthritic paws of IL-1ra(-/-) mice compared with the WT, and most of the cells that infiltrated into the joints of the IL-1ra(-/-) mice were CXCR2-expressing neutrophils. Administration of anti-CXCR2 Ab completely inhibited arthritis development. The anti-CXCR2 Ab decreased the number of neutrophils in the blood and also inhibited the migration of neutrophils to KC. These results suggested that the high susceptibility of IL-1ra(-/-) mice to anti-CII Ab-induced arthritis was due to the higher expression of chemotactic factors like KC and the sustained infiltration of CXCR2-expressing neutrophils into the joints.     

Frequency and clinical features of suicide attempts in elderly patients in Japan

The objective of this study was to investigate the clinical features of suicide attempts in elderly patients (≥65 years) in Japan. We enrolled 546 patients who attempted suicide and were hospitalized for inpatient treatment. Characteristics were compared between the elderly and non‐elderly patients. Compared with the non‐elderly group, the incidence of mood disorders was significantly higher and the average length of stay in the intensive care unit and the duration of hospitalization were significantly longer in the elderly group. Elderly patients hospitalized for attempted suicide were more likely to have mood disorders than the non‐elderly.     

Essential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages

Mycobacterium leprae (M. leprae), the causative agent of leprosy, parasitizes within the foamy or enlarged phagosome of macrophages where rich lipids accumulate. Although the mechanisms for lipid accumulation in the phagosome have been clarified, it is still unclear how such large amounts of lipids escape degradation. To further explore underlying mechanisms involved in lipid catabolism in M. leprae-infected host cells, we examined the expression of hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization and lipolysis, in human macrophage THP-1 cells. We found that infection by live M. leprae significantly suppressed HSL expression levels. This suppression was not observed with dead M. leprae or latex beads. Macrophage activation by peptidoglycan (PGN), the ligand for toll-like receptor 2 (TLR2), increased HSL expression; however, live M. leprae suppressed this increase. HSL expression was abolished in the slit-skin smear specimens from patients with lepromatous and borderline leprosy. In addition, the recovery of HSL expression was observed in patients who experienced a lepra reaction, which is a cell-mediated, delayed-type hypersensitivity immune response, or in patients who were successfully treated with multi-drug therapy. These results suggest that M. leprae suppresses lipid degradation through inhibition of HSL expression, and that the monitoring of HSL mRNA levels in slit-skin smear specimens may be a useful indicator of patient prognosis.     

Retention and viral suppression of newly diagnosed and known HIV positive pregnant women on Option B+ in Western Kenya

Kenya introduced universal antiretroviral treatment (ART) for pregnant and breastfeeding women living with HIV (Option B+) in 2014. A retrospective study was conducted to review consecutive records for HIV positive pregnant women presenting for antenatal care (ANC) at five clinics in western Kenya. Known positive women (KP :HIV diagnosis prior to current pregnancy) were compared to newly positive (NP) women regarding virologic suppression and retention in care. Among 165 women included, 71 (43%) NP and 94 (57%) KP, NP were younger (24.5 years (SD 4.6) vs. 28.1 years (SD 5.6) compared to KP (p?<?.001). Almost all NP (97%) were initiated on Option B+ while over half of KP (59%) started ART for clinical/immunological criteria (p?<?.0001). KPs were more likely than NPs to have a VL performed following Kenyan guidelines (64% vs. 31%; p?<?.001). Among those tested, virologic suppression was high in both groups (92% KP vs. 100% NP; p?=?.31). More KPs (82%) vs. NPs (66%) remained active in care at 15–18 months of follow-up (p?=?.02). Women newly diagnosed with HIV during pregnancy show poorer uptake of VL testing and worse retention in care than those diagnosed prior to pregnancy.     

Development of an immunochromatographic strip for simple detection of penicillin-binding protein 2'

Infections with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CNS) are a serious problem in hospitals because these bacteria produce penicillin-binding protein 2' (PBP2' or PBP2a), which shows low affinity to β-lactam antibiotics. Furthermore, the bacteria show resistance to a variety of antibiotics. Identification of these pathogens has been carried out mainly by the oxacillin susceptibility test, which takes several days to produce a reliable result. We developed a simple immunochromatographic test that enabled the detection of PBP2' within about 20 min. Anti-PBP2' monoclonal antibodies were produced by a hybridoma of recombinant PBP2' (rPBP2')-immunized mouse spleen cells and myeloma cells. The monoclonal antibodies reacted only with PBP2' of whole-cell extracts and showed no detectable cross-reactivity with extracts from other bacterial species tested so far. One of the monoclonal antibodies was conjugated with gold colloid particles, which react with PBP2', and another antibody was immobilized on a nitrocellulose membrane, which captures the PBP2'-gold colloid particle complex on a nitrocellulose strip. This strip was able to detect 1.0 ng of rPBP2' or 2.8 × 10(5) to 1.7 × 10(7) CFU of MRSA cells. The cross-reactivity test using 15 bacterial species and a Candida albicans strain showed no detectable false-positive results. The accuracy of this method in the detection of MRSA and MR-CNS appeared to be 100%, compared with the results obtained by PCR amplification of the PBP2' gene, mecA. This newly developed immunochromatographic test can be used for simple and accurate detection of PBP2'-producing cells in clinical laboratories.     

Anti–interleukin-6 autoantibodies in rheumatic diseases

Objective. To investigate the presence and the roles of anti–interleukin-6 (anti–IL-6) autoantibodies in rheumatic diseases, and to further elucidate clinical and pathophysiologic significance of anticytokine autoantibodies. Methods. Anti–IL-6 IgG autoantibodies were measured by the ¹²⁵I–IL-6 binding activity of IgG, which was isolated from serum by protein A–Sepharose. Results. Nine of 52 sera (17.3%) from patients with systemic sclerosis (SSc) contained anti–IL-6 antibodies, whereas only 1.9% of sera from normal subjects and 0–5% of sera from patients with other rheumatic diseases were positive for the antibodies. Moreover, anti–IL-6 autoantibodies were found predominantly among patients with the limited form of SSc (42.9%), compared with those with the diffuse form (7.9%). Conclusion. Anti–IL-6 IgG autoantibodies were detected in patients with SSc, particularly those with the limited form of the disease, at a significantly increased frequency compared with normal subjects and patients with other rheumatic diseases. These results suggest that the development of anti–IL-6 autoantibodies and IL-6 may have a role in the pathophysiology of SSc.