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Different immunological status and pathophysiologies exist between NMO and MS, and IL-6 may play important roles in the pathogenesis of NMO.

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Background: The discovery and development of novel biomarkers that could facilitate early diagnosis and thus prevent the progression of atherosclerosis-related diabetes mellitus (DM), cerebral infarction (CI), and cardiovascular disease (CVD) has garnered much research interest. Notably, recent reports have described a number of highly sensitive antibody markers. In this study, we aimed to identify additional antibody markers that would facilitate screening. Methods:The amplified luminescent proximity homogeneous assay (AlphaLISA) method, which incorporates glutathione-or streptavidin-donor beads and anti-human-IgG-acceptor beads, was used to evaluate serum antibody levels in serum samples. The protein array method was used for the initial screening, and peptide arrays were used to identify epitope sites. Results:The protein array identified SH3 domain-binding protein 5 (SH3BP5) as a target antigen of serum IgG antibodies in the sera of patients with atherosclerosis. We prepared recombinant glutathione S-transferase (GST)-fused SH3BP5 protein. Peptide arrays revealed that the epitope site recognized by serum antibodies is located within amino acids 161-174 of SH3BP5. AlphaLISA revealed significantly higher serum antibody levels against both the SH3BP5 protein and peptide in patients with DM, acute-phase CI, transient ischemic attack, CVD or chronic kidney disease (CKD), than in healthy donors. Furthermore, areas under the receiver operating characteristic curves of these antibodies were higher in patients with CKD and DM than in other patients. Spearman correlation analysis revealed associations between the serum antibody levels against SH3BP5 peptide and artery stenosis, hypertension, and smoking. Conclusions:The serum anti-SH3BP5 antibody marker appears to be useful for estimating the progress of atherosclerosis and may discriminate atherosclerosis associated with hypertension and/or habitual smoking.

and the OPDM_LRP12 Study Group IMPORTANCE Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown.OBJECTIVE To identify and characterize the clinicopathologic features of patients with OPDM_LRP12. DESIGN, SETTING, AND PARTICIPANTSThis case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot.MAIN OUTCOMES AND MEASURES Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics.RESULTS Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r 2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients. CONCLUSIONS AND RELEVANCEThis study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.