Efficacy and safety of belimumab combined with the standard regimen in treating children with lupus nephritis.

The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively. CONCLUSION: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low. WHAT IS KNOWN: • Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear. WHAT IS NEW: • This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events.

Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study in the Chinese Population.

Introduction: Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) is associated with a poor prognosis and high mortality; however, few studies about cardiac involvement in EGPA in the Chinese population are available. We conducted this study to determine the clinical characteristics and overall outcomes of Chinese EGPA patients with cardiac involvement. Materials and Methods: We retrospectively collected the clinical data of 83 patients diagnosed with EGPA and analyzed the differences between the patients with and without cardiac involvement. Results: The prevalence of cardiac involvement in EGPA in this cohort was 27.7%. Compared with those without cardiac involvement, EGPA patients with cardiac involvement tended to have a younger age at onset (mean ± SD: 38.4 ± 10.5 vs. 42.1 ± 15.9 years, respectively, p = 0.039), higher eosinophil count (median [IQR]: 5810 [4020-11090] vs. 2880 [1530-6570] n/µL, respectively, p = 0.004), higher disease activity assessed using the Birmingham vasculitis activity score (BVAS) (median [IQR]: 20 [16-28] vs. 15 [12-18], respectively, p = 0.001), and poorer prognosis (Five Factor Score [FFS] ≥ 1: 100% vs. 38.3%, respectively, p = 0.001). In the cardiac involvement group, 43.5% of patients were asymptomatic, but cardiac abnormalities could be detected by cardiac examinations. With appropriate treatment, the overall outcomes of EGPA patients with cardiac involvement in our cohort were good, with only 3 (13.0%) patients dying in the acute phase and no patients dying during follow-up. Conclusions: Cardiac involvement in EGPA was associated with a younger age at onset, higher eosinophil count, higher disease activity, and a poorer prognosis. Comprehensive cardiac examinations and appropriate treatment are essential to improve the prognosis of those with cardiac involvement.

Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4-Related Disease.

OBJECTIVE: To determine the number and function of follicular helper T (Tfh) cell subsets in IgG4-related disease (IgG4-RD). METHODS: Mononuclear cells from the peripheral blood and involved tissue of patients with IgG4-RD were assessed for Tfh cells and their subsets, and levels of B cell lymphoma 6 (Bcl-6), B lymphocyte-induced maturation protein 1 (BLIMP-1), and interleukin-21 (IL-21) messenger RNA (mRNA). Immunohistochemical and immunofluorescence techniques were used to assess the involved tissue of patients to determine the location of IL-21, Bcl-6, and CD4+CXCR5+ Tfh cells. Furthermore, the ability of circulating Tfh (cTfh) cell subsets to induce B cell proliferation, apoptosis, and differentiation and to produce IgG4 was explored in cell cocultures in vitro. RESULTS: Frequencies of cTfh cells were significantly increased in the peripheral blood of patients with IgG4-RD, and even higher frequencies were observed in the involved tissue. Percentages of programmed cell death protein 1 in CD4+CXCR5+ICOS+ cTfh cells were positively correlated with the serum levels of IgG and IgG4, IgG4:IgG ratio, number of involved organs, and frequency of CD19+CD24-CD38high plasmablasts/plasma cells. Levels of BLIMP-1 and IL-21 mRNA in peripheral CD4+ T cells were increased in patients with IgG4-RD compared to healthy controls, and this was correlated with the levels of serum IgG4. Moreover, in the involved tissue, Bcl-6, IL-21, and Tfh cells were highly expressed. Compared to cTfh cells from healthy controls, cTfh cells from patients with IgG4-RD could facilitate B cell proliferation and inhibit B cell apoptosis more efficiently, and enhanced the differentiation of naive B cells into switched memory B cells and plasmablasts/plasma cells, with a resultant increase in the secretion of IgG4. Notably, the cTfh1 and cTfh2 cell subsets were the most effective at providing B cell help. CONCLUSION: Tfh cell subsets are expanded in IgG4-RD and may play pivotal roles in the pathogenesis of the disease.

Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4-related diseases: a preliminary randomized controlled trial.

AIM: In order to evaluate the efficacy and safety of high versus medium doses of glucocorticoid therapy in remission induction of immunoglobulin G4-related disease (IgG4-RD), we set up a randomized controlled study. METHOD: Newly diagnosed IgG4-RD patients were randomly assigned to two groups: high doses of prednisone (0.8-1.0 mg/kg/day) and medium doses (0.5-0.6 mg/kg/day). Patients were assessed at weeks 0, 4, 12 and 24. The primary outcome was the remission rate at week 24. The secondary endpoints included IgG4-RD responder index (IgG4-RD RI), IgG and IgG4 levels. RESULTS: Twenty cases in each group finished the study. At week 24, the total response rates were 95% and 80% in high and medium dose groups, respectively. There was no significant difference between the two groups. IgG4-RD RI reduced from 14.9 to 3.0 in the high dose group, while in the medium dose group it was from 13.1 to 3.2. At week 24, the average level of IgG4 reduced from 1576 to 324 mg/dL and from 1445 to 684 mg/dL in the two groups, respectively. Relapsed patients had higher baseline IgG4-RD RI. There was no severe adverse effect shown in both groups. CONCLUSION: The effect of remission induction was similar in high and medium glucocorticoid groups. However, patients with more organs involved and higher IgG4-RD RI score at baseline might get more benefit with high dose glucocorticoid for remission induction.

Circulating plasmablasts/plasma cells: a potential biomarker for IgG4-related disease.

BACKGROUND: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a multisystem fibroinflammatory disease. We previously reported that a circulating cell population expressing CD19+CD24-CD38hi was increased in patients with IgG4-RD. In this study, we aimed to document that this cell population represented circulating plasmablasts/plasma cells, to identify the detailed phenotype and gene expression profile of these IgG4-secreting plasmablasts/plasma cells, and to determine whether this B-cell lineage subset could be a biomarker in IgG4-related disease (IgG4-RD). METHODS: A total of 42 untreated patients with IgG4-RD were evaluated. Peripheral B-cell subsets, including CD19+CD24-CD38hi plasmablasts/plasma cells, CD19+CD24+CD38- memory B cells, CD19+CD24intCD38int naïve B cells, and CD19+CD24hiCD38hi regulatory B cells, were assessed and sorted by flow cytometry. Microarray analysis was used to measure gene expression of circulating B-cell lineage subsets. Further characterization of CD19+CD24-CD38hi plasmablasts/plasma cells was carried out by evaluating additional surface markers, including CD27, CD95, and human leukocyte antigen (HLA)-DR, by flow cytometric assay. In addition, various B-cell lineage subsets were cultured in vitro and IgG4 concentrations were measured by cytometric bead array. RESULTS: In untreated patients with IgG4-RD, the peripheral CD19+CD24-CD38hi plasmablast/plasma cell subset was increased and positively correlated with serum IgG4 levels, the number of involved organs, and the IgG4-related Disease Responder Index. It decreased after treatment with glucocorticoids. Characterization of the plasmablast/plasma cell population by gene expression profiling documented a typical plasmablast/plasma cell signature with higher expression of X-box binding protein 1 and IFN regulatory factor 4, but lower expression of paired box gene 5 and B-cell lymphoma 6 protein. In addition, CD27, CD95, and HLA-DR were highly expressed on CD19+CD24-CD38hi plasmablasts/plasma cells from patients with IgG4-RD. Furthermore, CD19+CD24-CD38hi plasmablasts/plasma cells secreted more IgG4 than other B-cell populations. CONCLUSIONS: Circulating CD19+CD24-CD38hi plasmablasts/plasma cells are elevated in active IgG4-RD and decreased after glucocorticoid treatment. This IgG4-secreting plasmablast/plasma cell population might be a potentially useful biomarker for diagnosis and assessing response to treatment.