Disease-Modifying Treatments for Multiple Sclerosis Affect Measures of Cellular Immune Responses to EBNA-1 Peptides.

BACKGROUND AND OBJECTIVES: Epstein-Barr virus (EBV) has been strongly implicated in the pathogenesis of multiple sclerosis (MS). Despite this, there are no routinely used tests to measure cellular response to EBV. In this study, we analyzed the cellular response to EBV nuclear antigen-1 (EBNA-1) in people with MS (pwMS) using a whole blood assay. METHODS: This cross-sectional study took place in a dedicated MS clinic in a university hospital. We recruited healthy controls, people with epilepsy (PWE), and pwMS taking a range of disease-modifying treatments (DMTs) including natalizumab, anti-CD20 monoclonal antibodies (mAbs), dimethyl fumarate (DMF), and also treatment naïve. Whole blood samples were stimulated with commercially available PepTivator EBNA1 peptides and a control virus-cytomegalovirus (CMV) peptide. We recorded the cellular response to stimulation with both interferon gamma (IFN-γ) and interleukin-2 (IL-2). We also compared the cellular responses to EBNA1 with IgG responses to EBNA1, viral capsid antigen (VCA), and EBV viral load. RESULTS: We recruited 86 pwMS, with relapsing remitting MS, in this group, and we observed a higher level of cellular response recorded with IFN-γ (0.79 IU/mL ± 1.36) vs healthy controls (0.29 IU/mL ± 0.90, p = 0.0048) and PWE (0.17 IU/mL ± 0.33, p = 0.0088). Treatment with either anti-CD20 mAbs (0.28 IU/mL ± 0.57) or DMF (0.07 IU/mL ± 0.15) resulted in a cellular response equivalent to control levels or in PWE (p = 0.26). The results of recording IL-2 response were concordant with IFN-γ: with suppression also seen with anti-CD20 mAbs and DMF. By contrast, we did not record any differential effect of DMTs on the levels of IgG to either EBNA-1 or VCA. Nor did we observe differences in cellular response to cytomegalovirus between groups. DISCUSSION: This study demonstrates how testing and recording the cellular response to EBNA-1 in pwMS may be beneficial. EBNA-1 stimulation of whole blood samples produced higher levels of IFN-γ and IL-2 in pwMS compared with controls and PWE. In addition, we show a differential effect of currently available DMTs on this response. The functional assay deployed uses whole blood samples with minimal preprocessing suggesting that employment as a treatment response measure in clinical trials targeting EBV may be possible.

Case report: Dueling etiologies: Longitudinally extensive spinal cord lesion mimicking spinal cord infarct with simultaneous positive Lyme serology and amphiphysin antibody.

Background: Longitudinally extensive spinal cord lesions are challenging diagnostic entities as they are uncommon, but various etiologies can cause them. Case report: We report a case of a 55-year-old man with a past medical history of hypertension. He is an ex-smoker. He presented with chest pain, followed by right lower limb weakness, preceded by 2 weeks of constipation and voiding dysfunction. The examination revealed right lower limb mild flaccid paresis, absent reflexes, reduced anal tone, and urinary retention. His symptoms deteriorated over 24 h, and he developed severe flaccid paraparesis with impaired pinprick sensation below the T4 level. MRI spine showed an abnormal, non-enhancing signal in the anterior aspect of the spinal cord extending from the T4 level to the conus without associated edema. He was commenced on intravenous steroids and had significant improvement after one dose. The imaging was felt to be consistent with spinal cord infarction, and aspirin was started. The cerebrospinal fluid analysis showed elevated protein (0.8 mg/ml). Investigations for stroke and autoimmune pathologies were negative. The Lyme immunoblot confirmed intrathecal production of IgG to Borrelia antigens. The patient was started on ceftriaxone. The paraneoplastic screen identified amphiphysin antibodies. CT-TAP and PET-CT did not identify occult malignancy. The patient had a significant improvement over 2 months, strength was almost fully recovered, and autonomic functions returned to normal. Conclusion: We describe an unusual steroid-responsive, longitudinally extensive spinal cord lesion with radiological features of spinal cord infarct and a simultaneous finding of intrathecal Lyme antibodies and serum amphiphysin antibodies.

CVD Risk Factors in the Ukrainian Roma and Meta-Analysis of Their Prevalence in Roma Populations Worldwide.

The Roma population suffers from severe poverty, social exclusion, and some of the worst health conditions in the industrialized world. Herein, we report on cardiovascular disease (CVD) risk factors in the Ukrainian Roma and present a meta-analysis of the prevalence of CVD risk factors in 16 Roma populations worldwide. The meta-analyses of CVD risk factors in Roma (n = 16,552) vs. non-Roma majority population of the same country (n = 127,874) included publicly available data. Ukrainian field survey included 339 adults of both sexes and outcomes of interest were hypertension, body mass index (BMI), smoking, education, and employment status. Furthermore, 35.7% of the Ukrainian Roma were hypertensive, 69.3% unemployed, and 48.4% never went to school. Ukrainian Roma women were more likely to be underweight and more prone to be hypertensive, with odds of hypertension increasing with age, BMI, and positive smoking status. Meta-analyses showed that, in comparison with non-Roma worldwide, the Roma bear significantly higher risk factor loads related to smoking (OR = 2.850), diabetes (OR = 1.433), abdominal obesity (OR = 1.276), and metabolic syndrome (OR = 1.975), with lower loads for hypertension (OR = 0.607) and BMI ≥ 25 kg/m2 (OR = 0.872). To conclude, the CVD risk factors which are more common in Roma than in the majority population may reflect their poor health-related behaviors and inadequate access to health education.