Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus

BACKGROUND: An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth. METHODS: Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records. RESULTS: Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE. CONCLUSION: Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE

Long-term exposure to transportation noise and risk of incident stroke:A pooled study of nine scandinavian cohorts

BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through link-age to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle con-founders, and air pollution. RESULTS: During follow-up (median = 19:5 y), 11,056 stroke cases were identified. Road traffic noise (Lden ) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for indi-vidual-and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2:5 lm (PM2:5 ) and NO2 ]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR = 1:12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR = 0:94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise. https://doi.org/10.1289/EHP8949

The IL-23 axis and innate immunity in the airways

The Interleukin-23 (IL-23) axis is a communication system that integrates innate and adaptive immunity. When triggered by microbial stimuli, antigen presenting cells can secrete the cytokine IL-23, leading to the production of IL-17 and IL-22. These cytokines facilitate the recruitment of neutrophils that can eliminate microbes, but may also cause epithelial damage through extensive inflammation. At the same time, the IL-23 axis protects the epithelium through the production of antimicrobial peptides. The protective role of the IL-23 axis for local epithelial defence led us to ask whether inflammatory cells of the airway epithelium can produce IL-22, a cytokine associated with the IL-23 axis. We showed that airway macrophages responded to IL-23 and a bacterial stimulus with the secretion of IL-22. This constitutes a local and accessible source of IL-22 during activation of the innate arm of pulmonary host defence. The IL-23 axis leads to neutrophil recruitment which risks damaging epithelial tissue. Therefore, a strict regulation of the production of these cytokines is necessary. We showed that IL-17 exerts a negative feedback effect on IL-23, thus decreasing its own production. Further, the IL-17 receptor was present on macrophages demonstrating a prerequisite to this response. The airway epithelium is protected by antimicrobial peptides functioning as innate antibiotics, several of which are regulated by the IL-23 axis. We demonstrated the expression of two antimicrobial peptides, calprotectin and LL-37, in healthy human airways. Of these, only LL-37 was induced by the gram-negative bacterial stimulus endotoxin in this setting. This demonstrates the involvement of LL-37 in the innate immune response against gramnegative bacteria. Finally, we quantified cytokines associated with the IL-23 axis in smokers with and without chronic obstructive pulmonary disease. Airway IL-17 did not differ significantly between the groups, but plasma IL-22 was increased in smokers, demonstrating a smoking induced systemic effect on the IL-23 axis. Neutrophils in the airways displayed signs of activation and could be further activated by TNFα, indicating that the local microenvironment can affect neutrophil activation

B Cell Therapy in Systemic Lupus Erythematosus: From Rationale to Clinical Practice

B cell hyperactivity and breach of tolerance constitute hallmarks of systemic lupus erythematosus (SLE). The heterogeneity of disease manifestations and relatively rare prevalence of SLE have posed difficulties in trial design and contributed to a slow pace for drug development. The anti-BAFF monoclonal antibody belimumab is still the sole targeted therapy licensed for SLE, lending credence to the widely accepted notion that B cells play central roles in lupus pathogenesis. However, more therapeutic agents directed toward B cells or B cell-related pathways are used off-label or have been trialed in SLE. The anti-CD20 monoclonal antibody rituximab has been used to treat refractory SLE during the last two decades, and the anti-type I IFN receptor anifrolumab is currently awaiting approval after one phase III clinical trial which met its primary endpoint and one phase III trial which met key secondary endpoints. While the latter does not directly affect the maturation and antibody production activity of B cells, it is expected to affect the contribution of B cells in proinflammatory cytokine excretion. The proteasome inhibitor bortezomib, primarily directed toward the plasma cells, has been used in few severe cases as an escape regimen. Collectively, current clinical experience and primary results of ongoing clinical trials prophesy that B cell therapies of selective targets will have an established place in the future personalized therapeutic management of lupus patients.Funding Agencies|Swedish Rheumatism Association; King Gustaf Vs 80-year Anniversary foundation Professor Nanna Svartz Foundation; Ulla and Roland Gustafsson Foundation; Region Stockholm; Karolinska InstitutetKarolinska Institutet; Gothenburg Society of Medicine; Region Ostergotland (ALF); King Gustaf Vs 80-year Anniversary foundation; King Gustaf V and Queen Victorias Freemasons foundation</p

Additional file 1: of Research interest and activity among medical students in Gothenburg, Sweden, a cross-sectional study

English version of the questionnaire used in the study. (DOCX 109 kb

Additional file 3: of Research interest and activity among medical students in Gothenburg, Sweden, a cross-sectional study

Data from Statistics Sweden (SCB). (PDF 6 kb

HIV/AIDS awareness and risk behavior among students in Semey, Kazakhstan: a cross-sectional survey

Abstract Background Until recently, young people in Kazakhstan have been only moderately affected by the global HIV epidemic. Today, however, the HIV epidemic in Central Asia is one of the most rapidly increasing epidemics in the world. It is mainly concentrated to vulnerable groups such as intravenous drug users, sex workers, the purchasers of sexual services and the financially marginalized. Young, sexually active people may however be the gateway for the epidemic to the general population, and knowledge about their attitudes and behavior is therefore important in planning preventive measures. Methods To gather information about young students and their attitudes and knowledge about HIV/AIDS, we collected 600 structured questionnaires and made 23 semi-structured interviews among three groups of students. Response rate was 99%. Results Almost 99% of the respondents had heard of HIV/AIDS, and 89% could identify ways to protect oneself against sexually transmitted HIV/AIDS. The main routes of transmission, sexual contact without condom and intravenous drug use, were both identified by 97% of the students. Twenty-five percent of the female students and 75% of the male students had had one or more sexual partners. More than 30% of the young men had purchased sex, and homosexuality was widely stigmatized. Conclusion Risks for the spread of HIV/AIDS among young people in Kazakhstan include prostitution as well as stigmatization of the HIV positive and of homosexuals. Protective factors are good knowledge about risks and protection, and opportunities to talk and gather information about sexuality and HIV/AIDS.</p