Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.

Background Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis. Methods Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019). Results The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment. Conclusions Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.

To investigate the role of B cells in experimental, superantigen-mediated Staphylococcus aureus arthritis and sepsis, we used gene-targeted B-cell-deficient mice. The mice were inoculated intravenously with a toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus strain. The B-cell-deficient and thus agamma-globulinemic mice showed striking similarities to the wild-type control animals with respect to the development of arthritis, the mortality rate, and the rate of bacterial clearance. Surprisingly, we found that the levels of gamma interferon in serum were significantly lower (P < 0.0001) in B-cell-deficient mice than in the controls, possibly due to impaired superantigen presentation and a diminished expression of costimulatory molecules. In contrast, the levels of interleukin-4 (IL-4), IL-6, and IL-10 in serum were equal in both groups. Our findings demonstrate that neither mature B cells nor their products significantly contribute to the course of S. aureus-induced septic arthritis.We have previously described a murine model of hematogenously induced Staphylococcus aureus arthritis and sepsis (7,8). Using this model, approximately 80 to 90% of mice inoculated with S. aureus LS-1 develop clinical arthritis. Immunohistochemical analysis of arthritic joints demonstrated the presence of phagocytes and T cells, predominantly of the CD4 phenotype (4). The infected mice displayed increased levels of inflammatory cytokines, such as tumor necrosis factor and interleukin-6 (IL-6) in serum (7). We have also shown that toxic shock syndrome toxin 1 (TSST-1), a superantigen produced by S. aureus LS-1, contributes to the arthritogenicity of S. aureus (3,5). A series of studies using this model suggested that S. aureus arthritis is a T-cell-dependent and superantigen mediated disease.As to the role of B cells in S. aureus arthritis, we have found that a striking feature in this model is the occurrence of polyclonal B-cell activation with highly increased levels of immunoglobulins and autoantibodies in serum (7). Using X-linked immunodeficiency (xid) mice to investigate the contribution of the B1 subset of B cells to the development of septic arthritis, it was found that this defect provided resistance (21). Since the B1 subset is considered to be of importance in the production of autoantibodies, it was hypothesized that the outcome of the experiment might have been due to this fact.The aim of this study was to investigate if mature B cells, irrespective of their B1 or B2 phenotype, and their products including cytokines, autoantibodies, and antibodies to bacterial constituents would affect the outcome of S. aureus-induced arthritis and sepsis. We report here that a complete absence of mature B cells has no impact on the outcome of these very severe and life-threatening conditions. MATERIALS AND METHODSMice. Gene-targeted B-cell-deficient MT mice (C57BL/6 ϫ 129) (11) were backcrossed to B10.Q (H-2 q ) mice for eight generations and then further intercrossed for two generations to provide homozygous B10.Q mice lacking fu...

The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved significantly since the introduction of immunochemotherapy (rituximab [R] with cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP]). However, few outcome data are available for very elderly patients (≥ 80 years). Therefore, we compared all patients with DLBCL aged ≥ 80 years diagnosed in the Gothenburg area during two time periods (2006-2009, "post-R" and 1997-2000, "pre-R"). Forty and 30 patients were identified, corresponding to 23.5% and 20.5%, respectively, of the entire population with DLBCL. Estimated 3-year progression-free (PFS) and overall (OS) survival was better post-R than pre-R: 41% vs. 17% (p = 0.015) and 41% vs. 17% (p = 0.01), respectively. Fifty-three percent of post-R patients were treated with curative intent with a moderately reduced R-CHOP regimen (median relative dose intensity: 0.86). At a median follow-up of 29 months, the 3-year PFS and OS were 70% (p = 0.018) and 76% (p = 0.0089), respectively. In conclusion, moderately reduced R-CHOP is tolerable and effective for a considerable number of very elderly patients with DLBCL and high age by itself should not be a reason for excluding a patient with DLBCL from such treatment.