Background This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). Methods We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. Results All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P <  0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P <  0.01). Conclusions In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.

Objective To investigate the serum total antibody (immunoglobulin M and immunoglobulin G) titre against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain following BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination in Japanese rheumatic disease patients undergoing immunosuppressive therapy. Methods The serum antibody titre against SARS-CoV-2 spike protein was analysed in 123 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers who had received 2 doses of the BNT162b2 mRNA vaccine with at least 14 days elapsing since the second dose. Results The antibody titre in rheumatic disease patients was significantly lower than that in healthy subjects (p<0.0001). The antibody titres of the 41 patients who received biologics or Janus kinase inhibitors and the 47 patients who received conventional immunosuppressive agents were significantly lower than those of the 35 patients who did not receive immunosuppressive agents (p<0.0001 and p<0.0001, respectively). In addition, the mean antibody titre of the 43 patients on methotrexate was significantly lower than that of the 80 patients not on methotrexate (p=0.0017). Conclusion Immunogenicity to the BNT162b2 mRNA COVID-19 vaccine in rheumatic disease patients was found to be reduced under immunosuppressive treatment. In particular, methotrexate seems to be associated with a decreased antibody response.

Background Antineutrophil cytoplasmic antibodies (ANCA) and Anti-glomerular basement membrane (GBM) antibodies often induce rapidly progressive glomerulonephritis (RPGN). Some reports have demonstrated RPGN with the sequential appearance of ANCA then anti-GBM antibodies, suggesting that ANCA may induce the development of anti-GBM antibodies. Whereas, many reports have shown that the development of ANCA is associated with various infectious diseases, such as non-tuberculous mycobacterial infection. Case presentation A 65-year-old woman with pulmonary non-tuberculous mycobacterial (NTM) infection was monitored without treatment. One year later, serum myeloperoxidase (MPO)- ANCA were elevated (14.1 U/mL (normal value < 3.0 U/ml)). A high fever and RPGN appeared 1 year later, and serum MPO-ANCAs were 94.1 U/mL. Anti-GBM antibodies were also detected. A renal biopsy revealed crescentic glomerulonephritis with linear deposits of IgG and C3c along the GBM and interstitial inflammation with endarteritis of arterioles. The diagnosis was RPGN associated with anti-GBM nephritis and ANCA-associated vasculitis. Conclusion This report shows that preceding NTM infection may have induced ANCA and anti-GBM antibodies and caused the development of RPGN.

We investigated the effect of hydroxychloroquine (HCQ) as an add-on treatment to immunosuppressants on the expression of proinflammatory cytokines in patients with systemic lupus erythematosus. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and interleukin 1 receptor antagonist (IL-1ra) were measured immediately before and 3 months after treatment with oral HCQ. Among the 51 patients enrolled in the study, HCQ treatment led to significantly reduced serum levels of TNF-α, IL-6, IL-8, VEGF-A, IL-1ra, and IL-2 (p < 0.0001; p = 0.0006; p = 0.0460, p = 0.0177; p < 0.0001; p = 0.0282, respectively) and to decreased (but not significantly) levels of MIP-1α (p = 0.0746). No significant changes were observed in the serum MCP-1 levels before and after HCQ administration (p = 0.1402). Our results suggest that an add-on HCQ treatment modulates the expression of proinflammatory cytokines even in systemic lupus erythematosus patients with low disease activity.

Background:HCQ for SLE in Japan has been administered in many cases after approval. Therefore, the effect of additional administration of HCQ on low disease activity of SLE was considered to be clearer.Objectives:To clarify the effect of HCQ treatment on the control of disease activity in SLE patients.Methods:All SLE patients with low disease activity (LDA) enrolled in this study started additional HCQ treatment from January 2016. All patients with LDA enrolled in this study started HCQ treatment and had been receiving oral HCQ continuously for at least 3 months without using other immunosuppressive treatments or glucocorticoids. Disease activity was evaluated by SLEDAI, CLASI, and LLDAS, and serum complement values, anti-DNA antibodies, and pro-inflammatory cytokines were analyzed as immunological biomarkers before and after HCQ treatment.Results:52 of 100 patients were enrolled in this study (M:F; 4:48, average age; 40.6±13.4). 24 lupus nephritis patients were in sustained remission. 29 patients (56%) achieved LLDAS and 3 patients (6%) achieved clinical remission (CR) before HCQ administration.Of the 20 patients (38%) who did not achieve LLDAS before HCQ administration, the LLDAS achievement rates at 3, 6, and 12 months after additional HCQ were 47%, 59%, and 81% (including 12.5% of CR achievement rates), respectively.Serum levels of MRP8, MRP14, TNF-α, IL-6, VEGF-A, IL-1ra, MIP-1a and IL-2 decreased significantly 3 months after additional HCQ treatment. In addition, serum levels of MRP8, MRP14, TNF-α, IL-6 and IL-2 also decreased significantly 3 months after additional HCQ treatment despite achieving LLDAS or CR. The expressions of IFN-α didn’t decrease significantly in 9 cases that could be detected.The magnitude of the changes in serum MRP8, MRP14, IL-8 and Il-1ra levels in patients with a history of LN was significantly higher than in those without a history of LN. The magnitude of the reduction in serum MCP-1 levels in patients not achieving LLDAS with a history of LN was significantly higher than in those without a history of LN(p=0.046).The change of CLASI activity score was correlated with the change in serum levels of MRP14 and MCP-1 with univariate analysis (MRP14: r=-0.41, p=0.017, MCP-1: r=-0.58, p=0.0006). The change of serum C3 levels had a negative correlation with MCP-1(r=-0.33, p=0.022).The magnitude of the change in serum levels of MRP14, TNF-α, IL-8, MCP-1, MIP-1a and IL-1ra in patients achieving LLDAS were correlated with the change of CLASI activity score with univariate analysis (MRP14: r=-0.49, p=0.041, TNFα: r=0.74, p=0.0038, IL-1ra: r=0.66, p=0.038, MIP-1a: r=0.63, p=0.037, Figure 1). Moreover, the change of serum C3 and C4 levels in them had a negative correlation with the change of serum MCP-1 levels (Figure 2).Figure 1.Correlation between change of CLASI activity scores and serum MCP-1 levels in SLE patients with LLDAS (IL-8: r=0.77,p=,0.0007, MCP-1: r=0.80,p=,0.0001).Figure 2.Correlation between change of serum C3 and C4 levels and serum MCP-1 levels in SLE patients with LLDAS (C3: r=-0.40, p=0.028, C4: r=-0.37, p=0.047).Conclusion:Additional administration of HCQ is useful for cytokine control even in LLDAS-achieved cases, and particularly contributes to the improvement of skin lesion.In addition, regulation of IL-8 and MCP-1 is important for control of renal lesions of SLE, and more control of the activity of SLEThe effect of HCQ on IL-8 and MCP-1 is related to the control of renal lesions in SLE, so that disease activity of more SLE patients might be more controlled disease activity.References:[1]R Wakiya, et al. Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus. Lupus. 2019;28:826-833Disclosure of Interests:None declared