Background: Accumulating evidence supports a major role of B cells in multiple sclerosis (MS) pathogenesis. How B cells are recruited to the CNS is incompletely understood. Our objective was to study B-cell chemokine concentrations in MS, their relationship with disease activity, and how treatment with methylprednisolone and natalizumab affected the concentration in CSF.

Summary: Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex‐matched and age‐matched healthy individuals, and related the patient responses to disease activity, as indicated by magnetic resonance imaging. The MBP induced a dose‐dependent release of interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α) and interleukin‐10 (IL‐10) by patient‐derived MNCs. The patients’ cells produced higher amounts of IFN‐γ and TNF‐α, and lower amounts of IL‐10, than cells from healthy controls (P < 0·03 to P < 0·04). Five patients with MS and no controls, displayed MBP‐induced CD4⁺ T‐cell proliferation. These high‐responders exhibited enhanced production of IL‐17, IFN‐γ, IL‐5 and IL‐4 upon challenge with MBP, as compared with the remaining patients and the healthy controls (P < 0·002 to P < 0·01). A strong correlation was found between the MBP‐induced CD4⁺ T‐cell proliferation and production of IL‐17, IFN‐γ, IL‐5 and IL‐4 (P < 0·0001 to P < 0·01) within the patient group, and the production of IL‐17 and IL‐5 correlated with the number of active plaques on magnetic resonance images (P = 0·04 and P = 0·007). These data suggest that autoantigen‐driven CD4⁺ T‐cell proliferation and release of IL‐17 and IL‐5 may be associated with disease activity. Larger studies are needed to confirm this.

Background: microRNAs (miRNAs) regulate the expression of the genome at the post-transcriptional level. They play a role in autoimmunity and inflammation, and show potential for use as therapeutic targets in many diseases. With the recent detection of miRNAs in body fluids, the possibility for using miRNAs as diagnostic biomarkers has emerged. Objective: We assessed whether miRNAs contribute to the altered immune activation state in relapsing–remitting multiple sclerosis (RRMS) patients and investigated the possible use of miRNAs as diagnostic biomarkers in multiple sclerosis (MS). Methods: We performed global miRNA expression profiling analysis in peripheral blood mononuclear cells (PBMCs) and selected miRNAs were measured in plasma. We detected expression of miRNAs by real-time qPCR and compared results with cytokines related to inflammation and disease activity. Selected miRNAs were analyzed in PBMC subpopulations, after isolating them by magnetic bead separation. Results: We found that among validated miRNAs, let-7d correlated with the pro-inflammatory cytokine interleukin-1B. The miR-145 was 3-fold up-regulated in MS patients; its possible use as a diagnostic biomarker in PBMCs, plasma and serum was confirmed by ROC-curve analysis (Area under the curve (AUC) 0.785, p = 0.0004; 0.785, p = 0.004; 0.981, P < 0.0001, respectively). Conclusions: RRMS patients in remission had altered expression of miRNAs. We validated miR-145 as a potential diagnostic biomarker for the diagnosis of MS in blood, plasma and serum.

Vitamin D deficiency has increased in the last few decades owing to changing lifestyles and dietary habits.¹ Vitamin D is an essential hormone for bone mineralization² that begins in utero and continues throughout childhood until early adulthood, when peak bone mass is reached, which is an important determinant for osteoporosis later in life.^3,4 A decreased bone mineral status has been associated with risk of fractures already in childhood.⁵ Furthermore, severe vitamin D deficiency in childhood can lead to craniotabes and rickets,⁶ but studies examining the effect of maternal gestational vitamin D status on offspring anthropometrics and bone mineralization have shown contradictory results.

Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce.

Preoperative localization of the diseased parathyroid gland(s) in primary hyperparathyroidism allows for minimally invasive surgery. This study was designed to establish the optimal first-line preoperative imaging modality. Ninety-one patients were studied consecutively in a prospective head-to-head comparison of dual isotope (Tc-MIBI vs I) subtraction parathyroid scintigraphy (PS), dual-phase PS, 4-dimensional (4D) CT, and ultrasonography (US). Surgery, histological confirmation, and postoperative normalization of Ca and parathyroid hormone were the reference standard. Ninety-seven hyperfunctioning parathyroid glands (HPGs) were identified by the reference standard. Sensitivity and specificity for subtraction PS, dual-phase PS, 4D-CT, and US were 93%, 65%, 58%, and 57% as well as 99%, 99.6%, 86%, and 95%, respectively. Interrater agreement was excellent for subtraction PS (κ = 0.96) while only fair for 4D-CT (κ = 0.34). Pinhole imaging and subtraction of delayed images (the latter especially in case of a nodular thyroid gland) increased the sensitivity of subtraction PS. SPECT/low-dose CT did not increase sensitivity but aided in the exact localization of the HPGs. Of 7 negative subtraction PS studies, 4D-CT and US were able to locate 3 and 1 additional HPGs, respectively. Dual isotope pinhole subtraction PS has higher diagnostic accuracy compared with dual-phase PS, 4D-CT, and US as a first-line imaging study in primary hyperparathyroidism. In case of a negative scintigraphy or suspicion of multiglandular disease, 4D-CT and/or US is recommended as a second-line modality. However, diagnostic algorithms should be adapted in accordance with local availability and expertise.