Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases.

Objectives: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods: From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results: The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (ß: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases

Objectives To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

Effectiveness and safety of oral lactococci-based vaccine encoding triple common allergens to prevent airway allergy in mice.

Allergic airway disease is the most common chronic airway inflammatory disorder in developed countries. House dust mite, cockroach, and mold are the leading allergens in most tropical and subtropical countries, including Taiwan. As allergen avoidance is difficult for patients allergic to these perennial indoor allergens, allergen-specific immunotherapy (ASIT) is the only available allergen-specific and disease-modifying treatment. However, for patients sensitized to multiple allergens, ASIT using each corresponding allergen is cumbersome. In the present study, we developed a recombinant L. lactis vaccine against the three most common indoor aeroallergens and investigated its effectiveness for preventing respiratory allergy and safety in mice. Three recombinant clones of Der p 2 (mite), Per a 2 (roach), and Cla c 14 (mold) were constructed individually in pNZ8149 vector and then electroporated into host strain L.lactis NZ3900. BALB/c mice were fed with the triple vaccine 5 times per week for 4 weeks prior to sensitization. The effectiveness and safety profile were then determined. Oral administration of the triple vaccine significantly alleviated allergen-induced airway hyper-responsiveness in the vaccinated mice. The allergen-specific IgG2a was upregulated. IL-4 and IL-13 mRNA expressions as well as inflammatory cell infiltration in the lungs decreased significantly in the vaccinated groups. No body weight loss or abnormal findings in the liver and kidneys were found in any of the groups of mice. This is the first report to describe a triple-aeroallergen vaccine using a food-grade lactococcal expression system. We developed a convenient oral delivery system and intend to extend this research to develop a vaccination that can be self-administered at home by patients.

Single-Layer Inverted Internal Limiting Membrane Flap Versus Conventional Peel for Small- or Medium-Sized Full-Thickness Macular Holes.

PURPOSE: To analyze the outcomes of using an internal limiting membrane (ILM) flap and the conventional ILM peel technique for small- or medium-sized full-thickness macular hole (FTMH) repair. DESIGN: Retrospective, interventional case series. METHODS: Eyes with an FTMH ≤400 µm that underwent vitrectomy with a single-layer inverted ILM flap (flap group, 55 eyes) or an ILM peel (peel group, 62 eyes) were enrolled. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Primary hole closure was achieved in 54 (98%) and 60 (97%) eyes in the flap and peel groups, respectively. The preoperative and postoperative 12-month BCVA values were comparable between the groups but were significantly better in the flap than in the peel group at 1 month (mean ± SD logMAR: 0.83 ± 0.43 vs 1.14 ± 0.50; P = .001), 3 months (0.58 ± 0.33 vs 0.82 ± 0.43; P = .002), and 6 months (0.56 ± 0.32 vs. 0.72 ± 0.48; P = .028). In the flap group, foveal gliosis was less common than in the peel group at 1 month (P = .030), and restored external limiting membrane and interdigitation zone was more common at 3 months (P = .046 and P < .001, respectively). CONCLUSIONS: The single-layer ILM flap and conventional ILM peel techniques both closed FTMHs and improved vision. ILM flaps were associated with better visual outcomes up to 6 months postoperatively and should be considered in FTMHs ≤400 µm.

APLAR recommendations on the practice of telemedicine in rheumatology.

INTRODUCTION: The COVID-19 pandemic led to rapid and widespread adoption of telemedicine in rheumatology care. The Asia Pacific League of Associations for Rheumatology (APLAR) working group was tasked with developing evidence-based recommendations for rheumatology practice to guide maintenance of the highest possible standards of clinical care and to enable broad patient reach. MATERIALS AND METHODS: A systematic review of English-language articles related to telehealth in rheumatology was conducted on MEDLINE/PubMed, Web Of Science and Scopus. The strength of the evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach as well as the Oxford Levels of Evidence. The recommendations were developed using a modified Delphi technique to establish consensus. RESULTS: Three overarching principles and 13 recommendations were developed based on identified literature and consensus agreement. The overarching principles address telemedicine frameworks, decision-making, and modality. Recommendations 1-4 address patient suitability, triage, and when telemedicine should be offered to patients. Recommendations 5-10 cover the procedure, including the means, data safety, fail-safe mechanisms, and treat-to-target approach. Recommendations 11-13 focus on training and education related to telerheumatology. CONCLUSION: These recommendations provide guidance for the approach and use of telemedicine in rheumatology care to guide highest possible standards of clinical care and to enable equitable patient reach. However, since evidence in telemedicine care in rheumatology is limited and emerging, most recommendations will need further consideration when more data are available.