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.

BackgroundThe proportion of physicians undertaking doctoral studies is decreasing. Early recruitment of medical students could counteract this trend. This follow-up survey investigated research interest and activity among medical students at the Sahlgrenska Academy, Gothenburg, Sweden.MethodsA questionnaire was administered to all medical students at the Sahlgrenska Academy, as a follow-up to a 2006 survey. The Mann-Whitney U test was used for ordinal variables and the Fisher exact test for categorical variables. Data from Statistics Sweden was used to analyse the number of PhDs awarded to individuals who earned a medical degree in 2000–2012.ResultsOf the students, 16 % were already conducting and another 36 % wanted to conduct research during their studies. The interest was at the same level compared to 2006. The main reasons for conducting research consisted of an interest in scientific problems or the research topic, a wish for personal development or intellectual stimulation. Students engaged in research reported lack of time, increased workload and less time to study as hindering factors.ConclusionsRecruitment could be improved by offering improved and regular information, clarifying career paths, broadly announcing available projects, and creating new and expanding existing research programmes. The potential for recruitment of Gothenburg medical students to research is substantial, but students are hampered by lack of time, lack of supervisors and lack of information.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-016-0749-3) contains supplementary material, which is available to authorized users.

There is little information on mucins versus potential regulatory factors in the peripheral airway lumen of long-term smokers with (LTS+) and without (LTS−) chronic obstructive pulmonary disease (COPD). We explored these matters in bronchoalveolar lavage (BAL) samples from two study materials, both including LTS+ and LTS− with a very similar historic exposure to tobacco smoke, and healthy non-smokers (HNSs; n=4–20/group). Utilizing slot blot and immunodetection of processed (filtered and centrifuged), as well as unprocessed BAL samples from one of the materials, we compared the quantity and fraction of large complexes of mucins. All LTS displayed an enhanced (median) level of MUC5AC compared with HNS. LTS− displayed a higher level of large MUC5AC complexes than HNS while LTS+ displayed a similar trend. In all LTS, total MUC5AC correlated with blood leukocytes, BAL neutrophil elastase and net gelatinase activity. Large mucin complexes accounted for most MUC5B, without clear group differences. In all LTS, total MUC5B correlated with total MUC5AC and local bacteria. In the same groups, large MUC5B complexes correlated with serum cotinine. MUC1 was increased and correlated with BAL leukocytes in all LTS whereas MUC2 was very low and without clear group differences. Thus, the main part of MUC5AC and MUC5B is present as large complexes in the peripheral airway lumen and historic as well as current exposure to tobacco smoke emerge as potential regulatory factors, regardless of COPD per se. Bacteria, leukocytes and proteinases also constitute potential regulatory factors, of interest for future therapeutic strategies.

There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as neutrophils extravasate, and whether surface density of CD11b and CD62L differs between long-term tobacco smokers (LTS) with and without COPD compared with healthy never-smokers (HNS). Unstimulated blood neutrophils from LTS with (<i>n</i> = 5) and without (<i>n</i> = 9) COPD displayed lower surface density of CD62L compared with HNS (<i>n</i> = 8). In addition, surface density of CD11b was higher in bronchoalveolar lavage (BAL) neutrophils from LTS without COPD compared with those with COPD and HNS. Moreover, in BAL neutrophils from all study groups, CD62L was lower compared with matched blood neutrophils. In addition, BAL neutrophils responded with a further decrease in CD62L to ex vivo TNF stimulation. Thus, neutrophils in the airway lumen display a higher state of priming than systemic neutrophils and bear the potential to be further primed by local cytokines even with no smoking or the presence of COPD, findings that may represent a universal host defense mechanism against local bacteria. Moreover, systemic neutrophils are primed in LTS regardless of COPD. Further studies in larger materials are warranted to determine whether the priming of neutrophils is protective against COPD or merely preceding it.