BACKGROUND
B-cell dysregulation is central to the pathogenesis of childhood-onset systemic lupus erythematosus (cSLE), yet the B-cell immunophenotypes across disease states remain incompletely defined. This study aimed to investigate the mechanistic basis and clinical relevance of B-cell-mediated immune dysregulation in cSLE.
METHODS
Peripheral blood samples from 64 cSLE patients and 40 age- and sex-matched healthy controls (HCs) were analyzed using flow cytometry. The subsets were compared across disease states, including lupus low disease activity state (LLDAS), active disease, and clinical flare. Diagnostic performance was evaluated using logistic regression and receiver operating characteristic analyses.
RESULTS
Compared with HCs, patients with cSLE exhibited reduced unswitched memory B cells and expanded pathogenic subsets, including double-negative (DN) B cells, age-associated B cells (ABCs), short-lived plasma cells (SLPCs), and long-lived plasma cells (LLPCs) (all P < 0.05). LLPCs showed the strongest disease association [area under the curve (AUC) = 0.855] and a combined model further improved discrimination (AUC = 0.936). Active disease was characterized by expanded DN B cells, ABCs, SLPCs, and LLPCs (all P < 0.05). Clinical flare involved selective enrichment of ABCs, DN B cells, and plasma cells without further increase in total B cells. Of note, LLPCs remained elevated in LLDAS compared with HCs (P < 0.01). ABCs were negatively correlated with complement C3 levels (r = - 0.26, P = 0.04).
CONCLUSIONS
cSLE is characterized by distinct peripheral B-cell immunophenotypes across different clinical states, marked by expansion of ABCs and plasma-cell populations. Persistent LLPC enrichment during clinical quiescence suggests incomplete immunological restoration and may contribute to disease heterogeneity and relapse susceptibility.
Li-Yun Xu, Hui Chen, Yong-Zhen Li et al.· World Journal of Pediatrics· 0 citations
OBJECTIVES
Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a rare disorder caused by biallelic mutations in ACP5. This study systematically evaluates genetic landscape, clinical features, treatment, and transcriptomics in SPENCDI.
METHODS
Whole-exome sequencing was performed for genetic diagnosis of patients from multiple centers, and tartrate-resistant acid phosphatase (TRAP) activity was measured for novel variants. Previously reported cases were integrated with the current cohort for analysis of genotypes, clinical characteristics, laboratory findings, and treatment responses. Bulk and single-cell RNA sequencing investigated immune signaling alterations.
RESULTS
We identified 17 patients with ACP5 deficiency from Egypt and China, discovering five novel pathogenic variants (A260D, L257P, G32D, K190Nfs*22, and T305Nfs*12). Three novel missense variants were detected with loss of TRAP activity. Clinical manifestations involve multiple systems, with the skeletal system most frequently involved (32.31%), where skeletal dysplasia (94.32%) and short stature (81.82%) are the predominant features. Patients showed elevated inflammatory activity, with enrichment of the NF-κB, MAPK, and cell death pathways, as well as upregulation of type I interferon genes in monocytes. Enhanced IFN-γ signaling interactions between monocytes and Natural Killer cells were observed. Therapeutically, Prednisolone and Azathioprine were the most common effective drugs, while patients treated with the Janus kinase inhibitors Ruxolitinib or Upadacitinib achieved a partial response.
CONCLUSIONS
This study expanded the genetic and clinical spectrum of ACP5 deficiency. An upregulated interferon signature was revealed, and monocytes were identified as a major cellular source of inflammation. These results provide valuable insights for improving the diagnosis and treatment of SPENCDI.
Shiling Zhong, Shuangyue Ma, Yasmine El Chazli et al.· Arthritis & Rheumatology· 0 citations
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