Peptides from the variable region of specific antibodies are shared among lung cancer patients

Late diagnosis of lung cancer is still the main reason for high mortality rates in lung cancer. Lung cancer is a heterogeneous disease which induces an immune response to different tumor antigens. Several methods for searching autoantibodies have been described that are based on known purified antigen panels. The aim of our study is to find evidence that parts of the antigen-binding-domain of antibodies are shared among lung cancer patients. This was investigated by a novel approach based on sequencing antigen-binding- fragments (Fab) of immunoglobulins using proteomic techniques without the need of previously known antigen panels. From serum of 93 participants of the NELSON trial IgG was isolated and subsequently digested into Fab and Fc. Fab was purified from the digested mixture by SDS-PAGE. The Fab containing gel-bands were excised, tryptic digested and measured on a nano-LC-Orbitrap-Mass- spectrometry system. Multivariate analysis of the mass spectrometry data by linear canonical discriminant analysis combined with stepwise logistic regression resulted in a 12-antibody-peptide model which was able to distinguish lung cancer patients from controls in a high risk population with a sensitivity of 84% and specificity of 90%. With our Fab-purification combined Orbitrap-mass-spectrometry approach, we found peptides from the variable-parts of antibodies which are shared among lung cancer patients

Ischemic patterns assessed by positron emission tomography predict adverse outcome in patients with idiopathic dilated cardiomyopathy

Although patients with idiopathic dilated cardiomyopathy (DCM) have no coronary artery disease, regional impairment of myocardial perfusion combined with preserved metabolism has been found using positron emission tomography (PET). Our aim was to assess the prognostic relevance of PET-mismatch between stress myocardial perfusion and glucose uptake on clinical outcome in DCM. In 24 patients with DCM who underwent both myocardial perfusion and metabolism PET scanning, "mismatch" was assessed and the association with clinical outcome (hospitalization, mortality, and heart transplantation) was investigated. Mismatch was found in 16 patients (66.7%). Univariate analysis showed that the presence of mismatch was associated with adverse outcome (P = 0.03). After adjustment for sex and age, the association remained significant with an adjusted relative risk of 10.4 (95% CI 1.1-103; P = 0.04) for death, heart transplant, or hospitalization. Univariate analysis also showed that a higher extent of mismatch was significantly associated with adverse outcome (P = 0.02). After adjusting for sex and age, the association remained significant with an adjusted relative risk of 6.5 [95% CI 1.2-36; P = 0.03] for death, heart transplantation, or hospitalization. PET stress perfusion-metabolism mismatch, indicative for ischemia, is frequently found in DCM patients and related to a poorer outcome

Coeliac disease and rheumatoid arthritis: similar mechanisms, different antigens

Rheumatoid arthritis (RA) and coeliac disease are inflammatory diseases that both have a strong association with class II HLAs: individuals carrying HLA-DQ2.5 and/or HLA-DQ8 alleles have an increased risk of developing coeliac disease, whereas those carrying HLA-DR shared epitope alleles exhibit an increased risk of developing RA. Although the molecular basis of the association with specific HLA molecules in RA remains poorly defined, an immune response against post-translationally modified protein antigens is a hallmark of each disease. In RA, understanding of the pathogenetic role of B-cell responses to citrullinated antigens, including vimentin, fibrinogen and α-enolase, is rapidly growing. Moreover, insight into the role of HLAs in the pathogenesis of coeliac disease has been considerably advanced by the identification of T-cell responses to deamidated gluten antigens presented in conjunction with predisposing HLA-DQ2.5 molecules. This article briefly reviews these advances and draws parallels between the immune mechanisms leading to RA and coeliac disease, which point to a crucial role for T-cell–B-cell cooperation in the development of full-blown disease. Finally, the ways in which these novel insights are being exploited therapeutically to re-establish tolerance in patients with RA and coeliac disease are described

Drainage or lavage as a salvage manoeuvre after intrathecal drug errors:A systematic review with therapeutic recommendations

Study Objective: Cerebrospinal fluid (CSF) drainage and lavage are reported to reduce drug exposure after inadvertant intrathecal drug administration errors. This reviews aims to provide recommendations for this salvage technique, with regard to methodology, effectiveness and adverse events. Design: Systematic review. A search in the databases of Embase, Medline, Web of Science, Cochrane Central Register of Randomized Trials and Google Scholar was performed in 2022. Study eligibility criteria: All reports of individual patient data with CSF drainage or lavage with a percutaneous lumbar access for an intrathecal drug error were included. Measurements: The primary outcome is the description and count of CSF drainage or lavage, such as times and volume of drainage, volume of replacement and type of replacement fluid. Secondary outcomes are the effects, adverse events and overall outcome. Main results: 58 cases were found, of which 24 were paediatric cases. There was a large variance in methodology, with regard to volume t and type of replacement fluid. In 45% of the cases the intrathecal drug removal continued. The effects were specifically reported in 27 cases, all demonstrated drug removal based on drug concentrations in the CSF (n = 20) and clinical signs (n = 7). Adverse effects were sought for in 17 cases and found intracranial haemorrhage in 3 cases. No interventions were required for these adverse events and the only reported long-term sequelae in these three patients was short-term memory impairment up to 6 months after the event (n = 1). The overall outcome depended largely on the causative agent. Conclusions: This review shows that CSF drainage or lavage leads to intrathecal drug removal, but it is unsure if this intervention leads to improved overall patient outcome. Based on aggregated data from case reports, we provide recommendations that may guide clinicians. The risk-benefit ratio should be weighed on a case-to-case basis.</p