Background and purposeThe aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to... Show moreBackground and purposeThe aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response.MethodsPatients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E-headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS-D and CES-D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti-CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables.ResultsIn total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti-CGRP medication was positively associated with a reduction in the HADS-D (β = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES-D (β = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09).ConclusionAnti-CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab. Show less
Lerkvaleekul, B.; Veldkamp, S.R.; Wal, M.M. van der; Schatorje, E.J.H.; Kamphuis, S.S.M.; Berg, J.M. van den; ... ; Wijk, F. van 2021
Objective JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a... Show moreObjective JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM. Methods Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up. The expression levels of five type I IFN-stimulated genes, MX1, IFI44, IFI44L, LY6E and IFIT3, were measured by RT-qPCR to determine the IFN signature and calculate an IFN score. IFN-inducible plasma proteins CXCL10 and galectin-9 were measured by multiplex immunoassay. Results Siglec-1 and IFN score were increased in JDM patients compared with controls and correlated with clinical disease activity. Stratification of patients by Siglec-1 expression at diagnosis identified those with high Siglec-1 expression as having a higher risk of requiring treatment intensification within the first 3 months after diagnosis (55% vs 0% of patients, P = 0.01). Siglec-1 expression strongly correlated with plasma levels of previously validated biomarkers CXCL10 (r(s) = 0.81, P < 0.0001) and galectin-9 (r(s) = 0.83, P < 0.0001), and was superior to the IFN score in predicting treatment response (area under the curve 0.87 vs 0.53, P = 0.01). Conclusion Siglec-1 on monocytes is a novel IFN-inducible biomarker in JDM that correlates with clinical disease activity and identifies patients at risk for a suboptimal treatment response. Further studies are required to validate these findings and their clinical potential. Show less
Variants in the Melanocortin 1 Receptor (MC1R) gene have been associated with an increased risk of melanoma, but the role in nevus count is unclear. We investigated if specificMC1Rgene variants or... Show moreVariants in the Melanocortin 1 Receptor (MC1R) gene have been associated with an increased risk of melanoma, but the role in nevus count is unclear. We investigated if specificMC1Rgene variants or the number ofMC1Rgene variants and phenotypical features were associated with nevus count. A total of 494 participants of the 'Leiden skin cancer study' were included and the MC1R gene coding sequence was analysed by single-strand conformation polymorphism analysis followed by sequencing of unknown variants. The association betweenMC1Rgene variants and nevus count and the association between age, gender and phenotypical features and nevus count were studied using the Chi-square test. Study of nine frequently occurringMC1Rgene variants in participants without skin cancer (n = 203) showed that the 'r' Val60Leu variant was significantly associated with high nevus count (>50 nevi) (P = 0.017). This association was very strong among women (P < 0.001), but not present among men. Having one or twoMC1Rvariants in general did not show a significant difference in the nevus count. Hair colour, skin type, eye colour and age were not significantly associated with nevus count, whereas gender showed a significant association (P = 0.008), with the highest nevus counts in female. The Val60Leu variant of the MC1R gene could be a promising candidate as an independent predictor of high nevus count, particularly in women. This information about the genetic makeup could promote personalized follow-up strategies and might help to prevent skin cancer in the future. Show less
Dharma, S.; Hapsari, R.; Siswanto, B.B.; Laarse, A. van der; Jukema, J.W. 2015
