Background Optic neuritis (ON) can occur as an isolated episode or will develop to multiple sclerosis (MS) a chronic autoimmune disease. What predicts ON progression to MS remains poorly understood. Methods We characterised the antibody epitope repertoire in three independent clinical cohorts (discovery ( n = 62), validation ( n = 20) and external cohort ( n = 421)) using mimotope variation analysis (MVA), a next generation phage display technology to identify epitopes that associate with prognosis of ON. Findings We observed distinct epitope profiles for ON, MS and the controls, whereas epitope repertoires of sera and CSF were highly similar. Two unique and highly immunogenic epitopes A and B were detected in subjects with ON progressing to MS. These epitopes A and B were strongly associated with herpesviral antigens (VCA p18 of Epstein-Barr virus (EBV); gB of Cytomegalovirus (CMV)). ROC addressed 75% of MS subjects with ON onset correctly (at 75% sensitivity and 74.22% specificity) based on the two-epitope biomarker analysis. Interpretation This is the first report on epitope diagnostics for MS employing the unbiased strategy of MVA for identification of novel immunological features of disease. Funding The Estonian Ministry of Education, The Estonian Research Council (PRG573, PRG805 and PSG691), H2020-MSCA-RISE-2016 (SZTEST), H2020-NMBP-2017 (PANBIORA), Helsinki University Hospital, Mary and Georg C. Ehrnrooth, Finnish Eye, Sigrid Jusélius and Magnus Ehrnrooth Foundations.
. Purpose: To analyse the frequency of neuromyelitis optica (NMO) among consecutive optic neuritis (ON) patients in Southern Finland and the feasibility of Aquaporin‐4 (AQP4) autoantibody assay in the diagnosis of NMO. Methods: Consecutive patients with symptoms suggestive of acute ON and managed in the Helsinki University Central Hospital were evaluated critically screened for AQP4 autoantibody during a 47.5‐month period. The antibodies were determined using radioimmunoprecipitation method. AQP4 index >15 was considered positive, 10–15 borderline and <10 normal. Brain magnetic resonance imaging (MRI) was performed for all patients. Results: Of the 300 patients with suspected ON, 191 were eventually diagnosed as ON, and 66 (35%) of them had a previous diagnosis or were diagnosed with multiple sclerosis (MS). Of the 125 patients without MS diagnosis, 62 (50%) had demyelinative lesions in MRI, which is a risk factor for developing MS. Two patients (1.1%; 95% CI 0.3–4.5) fulfilled the criteria of NMO. Positive AQP4 antibodies were found in three patients (1.6% 95% CI 0.3–4.5), one of them had NMO, one had MS and one became diagnosed with MS a month later. Borderline autoantibody levels were found in 10 patients, 7 of whom had MS. Conclusions: NMO is rare among ON patients in the population of Southern Finland. In this small cohort, the sensitivity and positive predictive values of the AQP4 autoantibody index for NMO were low, 1/2 and 1/3 respectively, and do not support initiating routine screening.
Purpose To evaluate the clinical features, diagnostic challenges, management, and prognosis of sebaceous carcinoma (SC) of the eyelids and periocular region in a Nordic country. Methods Patients were identified from the Finnish Cancer Registry and the Helsinki University Hospital databases during the 21‐year period 1998–2018. Age, sex, location, clinical and histopathologic diagnosis, treatment and outcome were registered. Results Sebaceous carcinoma (SC) was diagnosed in 32 patients. The incidence was 0.6 per million. Median age at the time of histopathologic diagnosis was 74 years, and 72% of patients were women. Diagnostic delay was often long, median 12 months. The most common cause for delay was misdiagnosis (72%): a chalazion in 34% and a benign tumour in 22%. The most common location was the upper eyelid (53%) and tumour type a solitary nodule (94%). The SC was not correctly diagnosed in 12 (40%) of 30 preoperative biopsies. The treatment for 31 (97%) patients was complete surgical removal with reconstruction. Conjunctival intraepithelial growth was found in 50%. The leading postoperative problem was ocular irritation (30%). During a median follow‐up of 58 months, two patients (6%) experienced a local recurrence and one patient died from metastatic SC. Conclusions The estimated incidence of SC in Finland was somewhat higher than in other Western countries. The diagnosis was often markedly delayed. Especially differentiation from chalazion continues to be essential. To improve outcomes, it is essential to inform the pathologist about the possibility of SC in eyelid biopsies and specimens and ideally submit them to an ophthalmic pathology service.
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