Relationship between stigma and infertility-related stress among couples undergoing AID: The mediating role of communication patterns.

Infertility can be stressful for infertile couples. This study aims to examine the intra-dyadic associations between stigma, communication patterns, and infertility-related stress in couples undergoing artificial insemination by donor semen (AID). This cross-sectional study was conducted from January to April 2021. Two hundred and three couples undergoing AID were recruited from a reproductive centre in China. All of the couples completed a two-item stigma questionnaire, Communication Pattern Questionnaire, and Fertility Problem Inventory. The actor-partner interdependence mediation analysis was performed using AMOS 23.0. The analysis demonstrated significant actor-actor effects for couples undergoing AID. More specifically, higher levels of stigma among wives and husbands were associated with more negative communication patterns, thereby increasing their own infertility-related stress. Simultaneously, there was a significant partner-actor effect among infertile wives, demonstrating that the husband's stigma can affect his wife's infertility-related stress by influencing her communication patterns. Couples undergoing AID experience increased infertility-related stress when they have high levels of stigma and negative communication patterns, and husbands' stigma is correlated to wives' communication patterns. Therefore, dyadic interventions aiming to improving stigma and enhancing positive communication may be conducive to reducing infertility-related stress.

The change of intimate relationship between people with Alzheimer's disease and their adult child caregivers: An interpretative phenomenological analysis.

This study aims to explore the change of intimate relationship between people with Alzheimer's disease and their adult child caregivers as the disease progresses. Twelve adult child caregivers were recruited through purposive sampling. Explanatory phenomenological analysis was conducted to analyse data collected by semi-structured in-depth interviews. This study found a dynamically changing relationship between adult child caregivers and their parents with Alzheimer's disease during care giving that evolved with the progress of the disease. The relationship was the most intimate in the middle stage of the disease for most caregivers and a new reciprocal relationship developed due to caregiving. Caregivers experienced different degrees of self-growth when providing care, though caregiver burdens were common. The positive experience and perception of caregivers were important for improving the quality of life for adult child caregivers of people with Alzheimer's disease.

Responsiveness to Tocilizumab in Anti-Acetylcholine Receptor-Positive Generalized Myasthenia Gravis.

Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy and safety in patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG). We performed a prospective, open-label, single-arm study in patients with gMG in a 48-week follow-up. All patients were AChR+ and were given tocilizumab by intravenous infusion at a dose of 8 mg/kg at intervals of 4 weeks. The primary endpoint was mean change from baseline in quantitative MG (QMG) score at week 12. The secondary endpoints were mean changes from baseline in MG activities of daily living (MG-ADL) score, AChR-ab titers, and the dosage of oral prednisone at week 12. At week 48, QMG, MG-ADL, and the use of prednisone were also evaluated. Fourteen gMG patients were enrolled and all of them completed the study. Tocilizumab treatment started 8 (4-192) months after the onset of gMG. During tocilizumab treatment, the QMG score was significantly decreased from 15.5 (interqualile range, 9-26) at baseline to 4 (0-9) at week 12 (p < 0.001). The change of ADL was decreased from 14.5(11-19) at baseline to 4 (0-19) at week 12 (p < 0.001) and the change of AChR-ab titers from 15 (7.5-19) at baseline to 6.8 (11.6-4.3) at week 12 (p < 0.001). The dosage of prednisone decreased from baseline 60 (20-65) mg/d to 30 (30-50) mg/d at week 12 (p < 0.001). By the end of the study, the QMG score was 2 (0-7) and MG-ADL score was 1.5 (0-6). 12 (85.7%) patients achieved minimal manifestations. 4 (28.6%) patients were able to discontinue prednisone. No patients experienced exacerbation at the end of the study. No serious adverse events were observed during follow-up. Tocilizumab treatment was associated with a good clinical response and safety over a 48-week observation period, as evidenced by significant improvements in QMG and MG-ADL.

Bruton's tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well as astrocyte-microglia interaction, which both contribute to evolution of NMOSD lesions. MAIN BODY: Through transcriptomic and flow cytometry analyses, we found that Bruton's tyrosine kinase (BTK), a crucial protein of B-cell receptor was upregulated both in the blood and cerebrospinal fluid of NMOSD patients. Blockade of BTK with zanubrutinib, a highly specific BTK inhibitor, mitigated the activation and maturation of B cells and reduced production of causal aquaporin-4 (AQP4) autoantibodies. In a mouse model of NMO, we found that both BTK and pBTK expression were significantly increased in microglia. Transmission electron microscope scan demonstrated that BTK inhibitor ameliorated demyelination, edema, and axonal injury in NMO mice. In the same mice colocalization of GFAP and Iba-1 immunofluorescence indicated a noticeable increase of astrocytes-microglia interaction, which was alleviated by zanubrutinib. The smart-seq analysis demonstrated that treatment with BTK inhibitor instigated microglial transcriptome changes including downregulation of chemokine-related genes and genes involved in the top 5 biological processes related to cell adhesion and migration, which are likely responsible for the reduced crosstalk of microglia and astrocytes. CONCLUSIONS: Our results show that BTK activity is enhanced both in B cells and microglia and BTK inhibition contributes to the amelioration of NMOSD pathology. These data collectively reveal the mechanism of action of BTK inhibition and corroborate BTK as a viable therapeutic target.

Experimental and theoretic mechanism of successive adsorption of oppositely charged Cu(II) and Cr(VI) onto amine-rich cellulose adsorbent.

A novel layer-by-layer adsorption was proposed and used for adsorption of Cu(II) and Cr(VI) on the pre-bleached sawdust cellulose coated with polyethylenimine (PSC-PEI). It was found that PSC-PEI loaded with Cu(II) cations was favorable for Cr(VI) anions adsorption. The maximum adsorption capacities estimated by Langmuir model for Cu(II) and Cr(VI) were 80.0 and 93.5 mg/g, respectively. The kinetic regression results, as fitted by the pseudo-second order model, revealed that the rate constant (k2) for Cr(VI) at 0.07 g/mg/min is significantly greater than that observed for Cu(II) at 0.02 g/mg/min, indicating that PSC-PEI exhibited a stronger affinity towards Cr(VI). The first-layer adsorption mechanism for Cu(II) involved the formation of copper-amine complex. Zeta potential and XPS results revealed that the second-layer adsorption of Cr(VI) mainly involved electrostatic attraction and redox reaction. The simulated results for dynamic column test showed good agreement between the theoretical values and the experimental values. The mass transfer mechanism indicated that Cu(II) adsorption was dependent on external mass transfer process, while the internal mass transfer is the rate-determining step for Cr(VI) adsorption. The saturated adsorbent was regenerated by washing with 5% NaOH and 5% H2SO4 solutions and the adsorption ability of more than 70% was sustained after three cycles of regeneration. This study demonstrated that the oppositely charged Cu(II) cations and Cr(VI) anions could be effectively removed by amine-rich cellulose adsorbent from wastewater through layer-by-layer adsorption.

Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a severe neurological inflammatory disease mainly caused by pathogenic aquaporin-4 antibodies (AQP4-IgG). The safety and efficacy of the neonatal Fc receptor antagonist batoclimab addition to conventional intravenous methylprednisolone pulse (IVMP) therapy in patients with NMOSD acute attacks was assessed. METHODS: In an open-label, dose-escalation phase 1b study, NMOSD patients with acute myelitis and/or optic neuritis received four doses of weekly subcutaneous injections of either 340 mg or 680 mg batoclimab with concurrent IVMP and were followed up for 27 weeks. The primary end-points were safety and tolerability. Secondary end-points included pharmacodynamics and efficacy, with key efficacy assessment at week 4. RESULTS: In total nine NMOSD patients were enrolled, including two and seven in the 340 and 680 mg groups. Five patients had acute myelitis, while the remaining four had unilateral optic neuritis. Batoclimab add-on therapy had an overall good safety profile without serious adverse events. In the 680 mg group, mean immunoglobulin G (IgG) reached its maximum reduction at the last dose (day 22). In the meantime, AQP4-IgG was undetectable in six of seven subjects whose baseline AQP4-IgG titers ranged from 1:32 to 1:320. Expanded Disability Status Scale score was reduced by 1.3 ± 0.4 at week 4 (2.7 ± 1.3) compared with baseline (4.0 ± 1.0). CONCLUSIONS: Batoclimab add-on therapy to IVMP is safe and tolerated in patients with NMOSD. Preliminary evidence suggests a beneficial neurological effect. A randomized controlled trial would be needed to prove the efficacy.

A real-world study of interleukin-6 receptor blockade in patients with neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease that can cause permanent neurological disabilities. However, the interleukin-6 (IL-6) signaling pathway is a promising therapeutic target for relapse prevention. Therefore, this study evaluated the long-term effectiveness of tocilizumab, a humanized anti-IL-6 receptor antibody, for NMOSD. We enrolled 65 patients with NMOSD who received regular intravenous administration of tocilizumab (8 mg/kg) between October 2017 and January 2022. Then, we retrospectively collected data on the clinical characteristics and baseline glial fibrillary acidic protein (GFAP) and neurofilament light chain levels. The primary outcome was the annualized relapse rate (ARR). Risk factors were assessed using a multivariable logistic regression model. During the median follow-up of 34.1 (interquartile range: 25.5-39.3) months, 23% (15/65) of patients relapsed during tocilizumab treatment, but the median ARR decreased from 1.9 (range 0.12-6.29) to 0.1 (range 0-1.43, p < 0.0001). A prolonged infusion interval (> 4 weeks, odds ratio [OR]: 10.7, 95% confidence interval [CI]: 1.6-71.4, p = 0.014) and a baseline plasma GFAP level of > 220 pg/mL (OR: 20.6, 95% CI 3.3-129.4, p = 0.001) were risk factors for future relapses. During treatment, the median Expanded Disability Status Scale score significantly decreased in aquaporin-4 antibody-positive and -negative patients, but the pain did not considerably improve. There were no severe safety concerns. Tocilizumab treatment significantly reduced the relapse rate in patients with NMOSD. However, prolonged infusion intervals and high baseline plasma GFAP levels may increase the relapse risk during tocilizumab therapy.

The SsAtg1 Activating Autophagy Is Required for Sclerotia Formation and Pathogenicity in Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a necrotrophic phytopathogenic fungus that produces sclerotia. Sclerotia are essential components of the survival and disease cycle of this devastating pathogen. In this study, we analyzed comparative transcriptomics of hyphae and sclerotia. A total of 1959 differentially expressed genes, 919 down-regulated and 1040 up-regulated, were identified. Transcriptomes data provide the possibility to precisely comprehend the sclerotia development. We further analyzed the differentially expressed genes (DEGs) in sclerotia to explore the molecular mechanism of sclerotia development, which include ribosome biogenesis and translation, melanin biosynthesis, autophagy and reactivate oxygen metabolism. Among these, the autophagy-related gene SsAtg1 was up-regulated in sclerotia. Atg1 homologs play critical roles in autophagy, a ubiquitous and evolutionarily highly conserved cellular mechanism for turnover of intracellular materials in eukaryotes. Therefore, we investigated the function of SsAtg1 to explore the function of the autophagy pathway in S. sclerotiorum. Deficiency of SsAtg1 inhibited autophagosome accumulation in the vacuoles of nitrogen-starved cells. Notably, ΔSsAtg1 was unable to form sclerotia and displayed defects in vegetative growth under conditions of nutrient restriction. Furthermore, the development and penetration of the compound appressoria in ΔSsAtg1 was abnormal. Pathogenicity analysis showed that SsAtg1 was required for full virulence of S. sclerotiorum. Taken together, these results indicate that SsAtg1 is a core autophagy-related gene that has vital functions in nutrient utilization, sclerotia development and pathogenicity in S. sclerotiorum.

Direct Electron Transfer from Upconversion Graphene Quantum Dots to TiO2 Enabling Infrared Light-Driven Overall Water Splitting.

Utilization of infrared light in photocatalytic water splitting is highly important yet challenging given its large proportion in sunlight. Although upconversion material may photogenerate electrons with sufficient energy, the electron transfer between upconversion material and semiconductor is inefficient limiting overall photocatalytic performance. In this work, a TiO2/graphene quantum dot (GQD) hybrid system has been designed with intimate interface, which enables highly efficient transfer of photogenerated electrons from GQDs to TiO2. The designed hybrid material with high photogenerated electron density displays photocatalytic activity under infrared light (20 mW cm-2) for overall water splitting (H2: 60.4 µmol gcat. -1 h-1 and O2: 30.0 µmol gcat. -1 h-1). With infrared light well harnessed, the system offers a solar-to-hydrogen (STH) efficiency of 0.80% in full solar spectrum. This work provides new insight into harnessing charge transfer between upconversion materials and semiconductor photocatalysts and opens a new avenue for designing photocatalysts toward working under infrared light.

A boronization-induced amorphous-crystalline interface on a Prussian blue analogue for efficient and stable seawater splitting.

A promising electrocatalyst with an amorphous-crystalline structure was designed through a NaBH4 reduction strategy. Such a surface-defective heterophase structure remarkably prevents the catalyst from corroding by hindering the transport of Cl-, resulting in efficient and stable overall seawater splitting.

The incidence and prevalence, diagnosis, and treatment of multiple sclerosis in China: a narrative review.

In 2018, the first list of rare diseases was published by the National Health Council of China, and multiple sclerosis (MS) was included in this list. Since then, the Chinese government and neurologists have made efforts to improve the clinical outcomes of patients with MS. During last few years, the incidence of MS in China was also investigated. The early and accurate diagnosis of MS was improved due to the application and promotion of magnetic resonance imaging and new diagnosis criteria. The market for and medical insurance access to disease-modifying therapies (DMTs) has been greatly accelerated, which has provided more treatment options and improved clinical outcomes for patients with MS, as well as reduced treatment cost. The pattern of MS in China is gradually changing, from delayed to early diagnosis, and from no treatment to treatment with DMTs during remission. This narrative review aimed to summarize an update to the status of MS in China, including incidence and prevalence, diagnosis, and available treatments. This would help to better understand the diagnosis and treatment gap between mainland China and other Asian regions, demonstrating the necessity of accurate diagnosis and optimized treatment of MS in China.

Highly Foldable, Super-Sensitive, and Transparent Nanocellulose/Ceramic/Polymer Cover Windows for Flexible OLED Displays.

Polymer cover windows are important components of flexible OLED displays but they easily generate wrinkles because of their weak folding resistance. Increasing the polymer thickness can improve the folding resistance but it decreases the touch sensitivity. Thus, fabricating highly foldable and supersensitive polymer cover windows is still challenging. Here, by incorporating cellulose nanocrystals (CNCs) and zirconia (ZrO2) into colorless polyimide (CPI), we developed a highly foldable and supersensitive hybrid cover window. Inspired by the theory of elasticity, we added rigid CNCs into CPI to improve the elastic modulus and hence the foldability. ZrO2 was introduced to improve dielectric properties, which leads to improved touch sensitivity. After these modifications, the elastic modulus of the cover windows was increased from 1432 to 2221 MPa, whereas its dielectric constant was increased from 2.95 to 3.46 (@1 × 106 Hz), resulting in significantly enhanced foldability and sensitivity. Meanwhile, because of the nano size of CNCs and ZrO2, the hybrid cover windows exhibit excellent optical properties with the transmittance of ∼88.1%@550 nm and haze of 2.39%. With improved and balanced mechanical, dielectric, and optical properties, these hybrid cover windows overcome current cover windows' defects and could be widely used in next-generation flexible displays.

Multiple intestinal hemangioma concurrent with low-grade appendiceal mucinous neoplasm presenting as intussusception-a case report and literature review.

BACKGROUND: Cases with intussusception caused by either intestinal hemangiomas or appendiceal mucinous neoplasms are extremely rare. CASE PRESENTATION: In this study, we reported a 47-year-old male presented with paroxysmal abdominal pain and postprandial bloating for 3 days. CT results indicated a high possibility of secondary intussusception in ascending colon. Histopathology indicated a mixed type of cavernous and capillary hemangioma, combined with low-grade appendiceal mucinous neoplasms (LAMNs) and intestinal obstruction. The patient underwent laparotomy and right hemicolectomy. Finally, the patient was followed up for 4 months with no disease progression. CONCLUSIONS: Rare studies reported the intestine hemangiomas coincided with appendix low-grade mucinous tumor. Its manifestations are not specific, which is a challenge in the preoperative diagnosis. For cases with intussusception that was not observed in time, it may lead to intestinal necrosis and diffuse peritonitis. Additionally, the ruptured mucinous tumor in the appendix may lead to pathogenesis of pseudomyxoma peritonei. Therefore, accurate diagnosis and appropriate surgery-based treatment contribute to the improvement of prognosis and severe outcomes among these patients.

Highly Soluble and Stable, High Release Rate Nanocellulose Codrug Delivery System of Curcumin and AuNPs for Dual Chemo-Photothermal Therapy.

As a natural antitumor drug, curcumin (CUR) has received increasing attention from researchers and patients due to its various medicinal properties. However, currently CUR is still restricted due to its low and stand-alone therapeutic effects that seriously limit its clinical application. Here, by using cellulose nanocrystals (CNCs) as a nanocarrier to load CUR and AuNPs simultaneously, we developed a hybrid nanoparticle as a codrug delivery system to enhance the low and stand-alone therapeutic effects of CUR. Aided with the encapsulation of ß-cyclodextrin (ßCD), both the solubility and the stability of CUR are greatly enhanced (solubility increased from 0.89 to 131.7 µg/mL). Owing to the unique rod-like morphology of CNCs, the system exhibits an outstanding loading capacity of 31.4 µg/mg. Under the heat effects of coloaded AuNPs, the system demonstrates a high release rate of 77.63%. Finally, with CNC as a bridge nanocarrier, all aforementioned functions were integrated into one hybrid nanoparticle. The all-in-one integration ensures CUR to have enhanced therapeutic effects and enables the delivery system to exhibit combined chemo-photothermal therapy outcomes. This work presents a significant step toward CUR's clinical application and provides a new strategy for effective and integrative treatment of tumor disease.

Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder.

Background: Interleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive. Objective: We investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis. Methods: Nineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS). Results: Improved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06-0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013). Conclusion: Early initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.

Longitudinal treatment responsiveness on plasma neurofilament light chain and glial fibrillary acidic protein levels in neuromyelitis optica spectrum disorder.

BACKGROUND: Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood. OBJECTIVE: To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD. METHODS: pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab (n = 29), rituximab (n = 23), oral prednisone (n = 16), and oral azathioprine or mycophenolate mofetil (n = 4). RESULTS: NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2-39.3) versus 11.5 (7.0-23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6-406.5) versus 68.7 (59.4-80.8) pg/mL; p < 0.001). Multivariable regression analyses indicated that baseline pNfL concentration was associated with age (p = 0.017), Expanded Disability Status Scale (EDSS) score (p = 0.002), and recent relapses (p < 0.001). Baseline pGFAP concentration was also associated with EDSS (p < 0.001) and recent relapses (p < 0.001). Compared with prednisone, tocilizumab and rituximab significantly reduced pNfL [tocilizumab, exp(ß), 0.65; 95% confidence interval (CI), 0.56-0.75; p < 0.001; rituximab, exp(ß), 0.79; 95% CI = 0.68-0.93; p = 0.005] and pGFAP levels [tocilizumab, exp(ß), 0.64; 95% CI, 0.51-0.80; p < 0.001; rituximab, exp(ß), 0.77; 95% CI, 0.61-0.98; p = 0.041] at the end of the study. The pNfL levels in the tocilizumab and rituximab groups were reduced to those of HCs [tocilizumab, 8.5 (7.06-17.90) pg/mL; p = 0.426; rituximab, 14.0 (9.94-21.80) pg/mL; p = 0.216]. However, the pGFAP levels did not decrease to those of HCs in NMOSD patients at the end of study [tocilizumab, 88.9 (63.4-131.8) pg/mL; p = 0.012; rituximab, 141.7 (90.8-192.7) pg/mL; p < 0.001]. CONCLUSION: pNfL and pGFAP may serve as biomarkers for NMOSD disease activity and treatment effects.

Flexible, transparent and tough silver nanowire/nanocellulose electrodes for flexible touch screen panels.

Flexible touch screen panel (f-TSP) has been emerging recently and metallic nanowire transparent conductive electrodes (TCEs) are its key components. However, most metallic nanowire (MNW) TCEs suffer from weak bonding strength between metal nanowire electrode layers and polymer substrates, which causes delamination of TCEs and produces serious declines in durability of f-TSPs. Here, we introduce AgS bonding and develop tough and strong electrode-substrate bonded MNW TCEs, which can enhance durability of f-TSPs significantly. We used silver nanowires (AgNWs) as metal conductive electrode and thiol-modified nanofibrillated cellulose (NFC-HS) nanopaper as substrates. Because of the existence of Ag from AgNWs and S from NFC-HS, strong AgS bonding was generated and tough TCEs were obtained. The TCEs exhibit excellent electrical stability, outstanding optical and electrical properties. The f-TSP devices integrated with the TCEs illustrate striking durability. This technique may provide a promising strategy to produce flexible and tough TCEs for next-generation high-durability f-TSPs.

B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease.

BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD. RESULTS: Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti-aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19- and CD19+ ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD. DISCUSSION: B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.

Optical Coherence Tomography Reveals Longitudinal Changes in Retinal Damage Under Different Treatments for Neuromyelitis Optica Spectrum Disorder.

Background: Progressive retinal neuroaxonal damage after acute optic neuritis may occur in neuromyelitis optica spectrum disorder (NMOSD). However, it is unclear if treatments used to prevent attacks influence neurodegeneration. Objectives: We aimed to investigate retinal damage in patients treated with disease-modifying drugs in a longitudinal study. Methods: We retrospectively included 50 patients with aquaporin 4-antibody-seropositive NMOSD. Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex (mGCC) thickness, total macular volume (TMV), and optic disc measures were acquired by spectral domain optical coherence tomography in patients treated with tocilizumab, rituximab, and azathioprine. Results: Longitudinally, in eyes with a history of ON (NMOSDON+), we observed annual thinning of mGCC [tocilizumab: -1.77 (-3.44, -0.09) µm, p = 0.041; rituximab: -2.03 (-3.58, -0.48) µm, p = 0.017; azathioprine: -1.79 (-2.22, -1.37) µm, p < 0.001], and pRNFL [tocilizumab: -2.07 (-0.75, -3.39) µm, p = 0.005; rituximab: -2.18 (-0.36, -4.00) µm, p = 0.023; azathioprine: -2.37 (-0.98, -3.75) µm, p = 0.003], reduced TMV [tocilizumab: -0.12 (-0.22, -0.01) mm3, p = 0.028; rituximab: -0.15 (-0.21, -0.08) mm3, p = 0.001; azathioprine: -0.12 (-0.20, -0.04) mm3, p = 0.006], and increased cup area [tocilizumab: 0.08 (-0.01, 0.16) mm2, p = 0.010; rituximab: 0.07 (0.01, 0.12) mm2, p = 0.019; azathioprine: 0.14 (0.02, 0.26) mm2, p = 0.023]. However, we detected no significant differences in annual changes in mGCC, pRNFL, TMV, and cup area between patients with tocilizumab, rituximab, and azathioprine in NMOSDON+ eyes. NMOSDON- eyes did not display mGCC or pRNFL thinning in patients treated with tocilizumab and rituximab. Intriguingly, we observed significant thinning of mGCC in patients treated with azathioprine compared with tocilizumab [-0.84 (-1.50, -0.18) µm vs. -0.19 (-0.87, 0.48) µm, p = 0.012] and rituximab [-0.84 (-1.50, -0.18) µm vs. -0.07 (-1.25, -2.51) µm, p = 0.015] in NMOSDON- eyes. Conclusions: This study demonstrated that retinal ganglion cell loss is independent of ON attacks in NMOSD. Tocilizumab and rituximab may delay mGCC thinning in NMOSDON- eyes compared with azathioprine.