Systemic autoinflammatory diseases (SAID) with inborn errors of cell death (IECD) are caused by overactivation of programmed cell death (PCD). However, the pathogenesis by which PCD leads to autoinflammation remains unclear. Here, we identified IECD patients carrying compound heterozygous RIPK1 variants K377E/R390G with autoinflammatory manifestations. Mechanistically, K377E and R390G mutations suppress NF-κB signaling and activate RIPK1 to promote cell death. CD8+ T cells of the patients displayed overactivated RIPK1 and excessive cell death, leading to an elevated CD4/CD8 ratio, which could also be detected in patients with cleavage-resistant mutation of RIPK1 or SHARPIN deficiency. We show that the increased cell death of CD8+ T cells promotes TNF and IFN-γ secretion to activate monocytes/macrophages, which triggers overproduction of proinflammatory cytokines. In addition, disruption of the communication between T cells and monocytes/macrophages through pharmacologic blockade of TNF and IFN attenuates proinflammatory cytokine production in macrophages and relieves all the symptoms in patients. This study further clarifies the mechanism for a group of IECD with SAID. Increased CD4/CD8 ratio and augmented RIPK1 activation in T cells provide potentially additional criteria for diagnosis of RIPK1-dependent IECD and a combination of TNF/JAK inhibitor could be an effective therapy for the diagnosed patients.

ObjectiveVasculo-Behçet’s syndrome (VBS) is a rare subtype of Behçet's syndrome (BS) characterized by vascular involvement, and its clinical profile in the pediatric population remains poorly characterized due to limited available data. This study aimed to describe the clinical characteristics, treatment strategies, and prognosis of pediatric VBS and to provide evidence for early identification and clinical management.MethodsA retrospective analysis was performed on the clinical data of 12 pediatric patients (≤18 years old) with VBS admitted to three centers from January 2013 to December 2023. Demographic data, clinical manifestations, laboratory results, treatment regimens, and follow-up outcomes were collected and analyzed.ResultsAmong the 12 patients, there were 5 boys and 7 girls, with a median age at onset of 9.5 years (range: 3–13 years). Arterial involvement was observed in 10/12 cases, mainly characterized by vascular wall thickening (6/12 cases) and luminal stenosis (5/12 cases), involving the pulmonary artery, aorta, and multiple other sites. Venous involvement was found in 5/12 cases, predominantly wall thickening with thrombosis (3/12 cases). Multisystem involvement was common, including the skin (10/12 cases), the gastrointestinal tract (9/12 cases), and the urinary system (6/12 cases). Inflammatory markers (CRP/ESR) were elevated in 11/12 cases. All patients received glucocorticoid therapy; 11/12 cases received it combined with immunosuppressants, 9/12 cases with biological agents, and 4/12 cases underwent surgical treatment. With a median follow-up of 2 years (range: 4 months–5 years), 8/12 cases achieved stable remission, 2/12 cases (both complicated by aneurysms) had multiple relapses, 1/12 case died of sudden cardiac death, and 1/12 case showed no improvement.ConclusionPediatric VBS is a rare and heterogeneous condition with frequent arterial involvement in this cohort. Vascular wall thickening may aid in the early recognition of this condition, while aneurysms may be associated with poorer outcomes.

OBJECTIVES:To explore the clinical features, diagnosis, treatment and prognosis of arterial involvement in paediatric Behçet's disease (BD) for clinical reference. METHODS:A retrospective cohort study analysed 76 paediatric BD patients (January 2013 - May 2024). Nineteen with arterial involvement were the experimental group, and 57 without vascular involvement were the control group. RESULTS:The experimental group mainly involved medium-sized (15/19, 78.95%), large-sized (13/19, 68.42%) or both (9/19, 47.37%) arteries, most commonly abdominal aorta (8/19, 42.11%), pulmonary artery (7/19, 36.84%) and femoral artery (7/19, 36.84%). Notably, we found a high prevalence of coronary artery involvement, exclusively manifesting as left main coronary artery dilation. Lesions were mainly wall thickening (9/19, 47.37%), lumen dilation (8/19, 42.11%) and stenosis (7/19, 36.84%). Compared with the control group, it had later onset age (11.0 vs. 7.0 years), shorter disease duration (6.0 vs. 24.0 months), and higher incidences of fever, multi-organ involvement (neurological, renal, cardiac), and elevated inflammatory markers including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). It also had more intensive treatment and surgery but had significantly higher rates of cerebrovascular accidents (15.79% vs. 0%), cardiac complications (31.58% vs. 0%), and mortality (10.53% vs. 0%). CONCLUSIONS:Paediatric BD with arterial involvement is a severe phenotype with a poor prognosis, characterized by intense inflammation and multi-organ damage. This underscores the critical need for early identification, aggressive treatment, and close monitoring to improve long-term outcomes.

BACKGROUND:Limited studies focused on characteristics of childhood-onset Takayasu arteritis (cTAK) throughout growth and development. METHODS:111 cTAK patients were recruited from six tertiary hospitals across China from January 2009 to December 2021. Patients were classified into infant group (<12 months), toddler and preschool group (≥12 months, <72 months), school-age group (≥72 months, <144 months) and adolescent group (≥144 months). RESULTS:Infantile cTAK patients tended to had a significantly higher proportion presenting with fever (91.7%, P-trend <0.001), and had significantly higher levels of C-reactive protein (CRP), white blood cells (WBC), platelet (PLT), and lower hemoglobin (HGB) compared to the other three groups (all P < 0.0125). Adolescent patients were more likely to present with headache (33.3%), dizziness (24.2%) and fatigue (51.5%; all P-trend < 0.001). Infantile patients were more likely to have coronary artery involvement (75.0%, P trend < 0.001). Adolescent patients were more likely to have superior mesenteric artery (36.4%, P trend = 0.005), carotid artery (30.3%, P trend = 0.003), and celiac trunk artery stenosis (27.3%, P trend = 0.005).Younger patients, especially infants, had a lower proportion of glucocorticoids use (P trend = 0.001). 73.0% (81/111) of patients were in remission, with a median follow-up time of 2.00 [2.00, 5.00] years. CONCLUSION:The age-specific patterns identified in this study offered valuable insights for a comprehensive understanding of cTAK. IMPACT:Infantile Takayasu arteritis patients tended to present with fever, elevated inflammatory biomarkers and coronary artery involvement. Adolescent patients were more likely to present with headache, dizziness and fatigue, with superior mesenteric artery, carotid artery involvement and celiac trunk artery stenosis. Clinical manifestations and vascular involvement of childhood-onset Takayasu arteritis differ across age groups. The clinical manifestations of childhood-onset Takayasu arteritis lack specificity. The age-specific patterns identified in this study may provide clues for early diagnosis.

This study aims to summarize and explore the clinical characteristics, treatment strategies, and follow-up outcomes of infantile Takayasu arteritis (TA) in the Chinese Han population. In this retrospective study, we collected clinical data, Kerr scores (the NIH score), and arterial involvement scores (AIS) of infants diagnosed with TA at the time of initial diagnosis and at 1, 3, 6, and 12 months following initial treatment. Prognostic differences between various treatment groups were also analyzed. A total of 18 Chinese Han infants with TA were included. The average age of onset was 85.06 ± 54.64 days. The main clinical manifestations included fever (77.78

This multicenter study aimed to address the heterogeneity of chronic recurrent multifocal osteomyelitis (CRMO) by identifying clinical subtypes through cluster analysis, exploring clinical features, treatment approaches, and short-term prognosis to improve management of pediatric CRMO. Data from 42 pediatric CRMO patients (47.6

OBJECTIVES:Childhood-onset Takayasu's arteritis (cTAK) is a rare disease with high recurrence rates, vascular complications, and mortality. This study aimed to identify the risk factors for poor prognosis in hospitalized patients with cTAK and develop a nomogram prediction model. METHODS:This was a prospective longitudinal multicenter cohort study. Cohorts were categorized into poor and good prognosis groups according to follow-up outcomes. Poor prognosis included vascular complications, disease recurrence, persistent non-remission, and cTAK-related death. RESULTS:Of the 111 patients, 73 (65.8%) and 38 (34.2%) were categorized into the good and poor prognosis groups, respectively, with a median follow-up of 36.0 [24.0, 60.0] months. Seven independent factors for poor prognosis of cTAK were identified: the Indian Takayasu Clinical Activity Score with the Acute-Phase Response (ITAS.A), internal carotid artery stenosis, external carotid artery stenosis, aortic insufficiency, mitral insufficiency, tricuspid insufficiency, and hypertensive heart disease (odds ratios: 1.20, 3.21, 3.57, 3.88, 9.08, 15.67, and 7.42, respectively; all P values < 0.05). The nomogram prediction model yielded an area under the receiver operating characteristic curve of 0.79. The C-index of the nomogram constructed based on the prediction model was 0.73. The accuracy of this model was 67.0% after bootstrapping for 1000 repetitions. CONCLUSION:We used easily accessible clinical and laboratory data to establish a nomogram model for predicting the probability of poor prognosis with hospitalized cTAK patients.

Introduction:Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I interferon (IFN) signaling. USP18 deficiency resulted in embryonic or neonatal lethality with severe systemic inflammation and neurological anomalies due to excessive IFN signatures. Importantly, additional disease-causing USP18 mutations remain to be identified and functionally characterized. Methods:Whole-exome sequencing was performed to identify pathogenic variants in two affected individuals. Extensive immunologic and functional assay were used to characterize inflammatory signatures and evaluate the impact of the variants on type I IFN signaling. Therapeutic intervention with the JAK inhibitor was administered and clinical response was monitored. Results:We identified novel USP18 biallelic mutations (p.C230X and p.G317S) in siblings with severe early-onset systemic inflammation. Patient PBMCs exhibited hypersensitivity to IFNα, leading to aberrant and prolonged activation of type I IFN signaling. Mechanistic studies revealed that the p.G317S variant disrupted the interaction between USP18 and ISG15, thereby impairing its negative regulatory function. Treatment with JAK inhibitor ruxolitinib alleviated the inflammatory phenotypes, followed by a sustained recovery. Conclusion:Novel biallelic mutations of USP18 lead to excessive type I IFN responses and severe interferonopathy. Our findings highlight a novel pathogenic mechanism in which impaired ISG15 binding compromises the regulatory function of USP18. The favorable clinical response to ruxolitinib suggests a promising therapeutic strategy.

Alternative splicing (AS) and alternative polyadenylation (APA) are widespread in the immune system. However, their precise role in juvenile dermatomyositis (JDM) remains unclear. Based on the polyadenylation sequencing platform, we described APA landscape of refractory JDM before and after autologous hematopoietic stem cell transplantation (AHSCT) treatment and revealed a shortened APA event of RNA splicing genes in refractory JDM. Notably, the use of the proximal polyadenylation site (PAS) in CELF2 is a distinctive feature of refractory JDM, which transitions to the distal PAS following AHSCT. This shift in PAS utilization from proximal to distal affects CELF2 expression efficiency in both cells and JDM, contributing to resistance to drug therapy and activation of the tumor necrosis factor (TNF) signaling pathway. As a splicing regulator, the utilization of proximal PAS in CELF2 induces a series of AS events in immune genes, including a novel insertion of exons 2 and 3 in Cathepsin B (CTSB), which may act as a potential disruptive factor for refractory JDM treatment. This study emphasized the impact of post-transcript regulation in the pathology of refractory JDM, highlighting the importance of regulating CELF2 PAS usage in the treatment of refractory JDM. Therefore, targeting proximal PAS usage may serve as a potential clinical biomarker and therapeutic strategy for managing refractory JDM.

Abstract Objective: Behçet’s syndrome (BS) can affect the vascular system, but little is known about the clinical manifestations of vasculo-BS (VBS) in children. The aim of this study was to explore the clinical characteristics of paediatric VBS. Methods: Clinical data of children with VBS treated at the Children's[A1] Hospital affiliated with the Capital Institute of Pediatrics and its sister hospitals from March 2013 to April 2023 were retrospectively analysed. Results: A total of 12 cases were identified, including 5 males and 7 females. Among them, 10 cases (83.3%) were treated at our department, accounting for 21.2% of the total BS cases in our department. The median age of onset was 9.5 years (range: 3-13 years). Vascular lesions were detected at the time of diagnosis in 10 cases, including 8 cases of pure arterial involvement ,2cases of pure venous involvementand and 2 cases of both arterial and venous involvement. Commonly affected arteries included the lower limb arteries (4/12), pulmonary artery, subclavian artery, renal artery, and superior mesenteric artery (3/12 each). Arterial wall thickening (6/12) and luminal stenosis (5/12) were common arterial lesions, with pulmonary artery thrombosis and arterial occlusion reported in 2 cases each. Venous wall thickening and luminal stenosis (2/12), as well as thrombosis (2/12), were common venous lesions, with superficial or deep venous thrombosis observed. Twelve cases received steroid therapy, 9 cases were treated using steroids combined with cyclophosphamide, and 8 cases were treated using steroids combined with thalidomide, while 9 cases using steroids combined with biologic agents. Surgical treatment was performed in 4 cases. Eight cases remained stable, 2 cases had recurrent activity, and 1 case died suddenly from cardiac causes. Conclusion: Paediatric VBS is rare, and vascular lesions are often identified concurrently with the diagnosis of BS. Arterial involvement is more common than venous involvement. Commonly affected arteries include the lower limb arteries, pulmonary artery, subclavian artery, renal artery, and superior mesenteric artery. Vascular lesions typically manifest as vascularwall thickening and/or luminal stenosis, with complications such as pulmonary artery embolism, arterial aneurysms, arterial occlusion, and venous thrombosis. Treatment with steroids combined with immunosuppressive agents and biologic agents is effective, but some cases still have a poor prognosis.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a key regulator of cell fate decision between pro-survival signaling and programmed cell death. The activation of RIPK1 is extensively modulated by posttranslational modification, such as ubiquitination. RIPK1 overactivation mediates autoinflammatory diseases in humans. However, the role of RIPK1 ubiquitination in human autoinflammatory diseases has not been reported, and the mechanism mediating the interaction of cell death and autoinflammation is largely unknown. Here, we report two patients carrying compound heterozygous RIPK1 variants K377E/R390G with recurrent fevers, lymphadenopathy and skin rashes. Mechanistically, K377E and R390G mutations impaired ubiquitination of RIPK1, which suppresses the formation of TNFR1 signaling complex (TNF-RSC) and NF-κB activation, resulting in the loss of CD8+ T cells mediated by RIPK1 activation-induced cell death in the patients. We reveal that the death of CD8+ T cells promotes the secretion of TNF and IFNγ to activate monocytes and macrophages, which triggers further production of proinflammatory cytokines to amplify autoinflammation. Disruption of the communication between T cells and monocytes/macrophages through pharmacologic blockade of TNF and IFNγ attenuated proinflammatory cytokine production in macrophages. Collectively, our results demonstrate a crucial role of RIPK1 ubiquitination in regulating CD8+ T cell death and restraining autoinflammation. Our study demonstrates the mechanism for a group of autoinflammatory diseases mediated by RIPK1 activation-induced cell death, and highlights an important role of CD8+ T cells in driving autoinflammation.### Competing Interest StatementJ.Y. is a consultant of Denali Therapeutics. The rest of authors declare no competing financial interests.### Funding StatementThe works of Q.Z. were supported by grants 82225022, 32141004 and 32321002 from the National Natural Science Foundation of China. The works of X.Y. were supported by the Hundred-Talent Program of Zhejiang University. J.D. received grant 32300618 from the National Natural Science Foundation of China. J.W. received the grant 2023M733104 from China Postdoctoral Science Foundation. L.G. received the grant LHDMY23H100005 from Zhejiang Provincial Natural Science Foundation of China.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Patients were evaluated under protocols approved by Institutional Review Board and Ethical Committee at the Children's Hospital of Zhejiang University School of Medicine (protocol 2021-IRB-172).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

We report a five-year-old boy who had been experiencing recurrent skin erosion in the right corner of the mouth (Supplementary Figure A), over the bilateral nostrils and bilateral external auditory canals (Supplementary Figure B) since age 2.5 years. At age four years, the boy developed vocal hoarseness due to vocal fold and epiglottic masses. He underwent laryngoscopy with excision of the masses. The pathological examination indicated mucosal inflammation with necrosis, ulcers, and inflammatory granulation tissue formation. At age 4.5 years, he had repeated skin erosion of the right thumb and index finger (Figure 1). Cytoplasmic antineutrophil cytoplasmic antibody testing was positive. Secretion next-generation sequencing revealed infections with human herpes virus, Enterococcus avium, Enterobacter cloacae, and Candida albicans. Auditory evoked potentials indicated conductive hearing loss in the right ear. Head magnetic resonance imaging showed sinusitis. Whole-exome genetic testing identified IL2RG mutations (c.270-14C>G, chrX-70330552).1 Therefore, the patient was diagnosed with X-linked combined immunodeficiency and granulomatosis with polyangiitis.2 Treatment included human intravenous immunoglobulin, fluconazole, acyclovir, compound sulfamethoxazole, and prednisone at a dose of 1mg/kg per day. Follow-up over the past two months showed improvement in the skin ulcers. Supported by the Clinical Cultivation Project of the Capital Institute of Pediatrics (project LCYJ-2023-12). Additional supplementary information cited in this article can be found online in the Supporting Information section (http://onlinelibrary.wiley.com/doi/10.1002/acr2.11708). Disclosure form Supplementary Figure A: Supplementary Figure B: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Objective To early recognise and improve the prognosis of children systemic lupus erythematosus (cSLE)-associated pancreatitis by summarising and analysing clinical features and prognosis data from 12 cases. Methods Retrospective analysis of clinical data from 12 cases of cSLE-associated pancreatitis diagnosed and treated from January 2016 to December 2021 at hospitals such as Children’s Hospital of Capital Institute of Paediatrics. Results The median SLEDAI-2K score for disease activity was 18.00 (range 12.25–21.00) in the case group and 10.00 (range 7.00–18.00) in the control group, with a statistically significant difference ( P < 0.05) between the two groups. The case group had a higher proportion of abdominal pain, vomiting, abdominal distension, pleural effusion, Raynaud’s phenomenon (RP), splenic infarction, and concurrent macrophage activation syndrome (MAS) than the control group, with a statistically significant difference ( P < 0.05). Serum ferritin (SF), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), amylase, and increased 24-h urine protein levels were statistically different between the two groups ( P < 0.05); platelet counts (PLT) reduction was also statistically different ( P < 0.05). The case group had a higher proportion of methylprednisolone pulse therapy, cyclophosphamide pulse therapy during remission induction, and therapeutic plasma exchange than the control group, with a statistically significant difference ( P < 0.05) between the two. Conclusion CSLE-associated pancreatitis has a high fatality rate. The presence of RP, splenic infarction, pleural effusion, and MAS warrants attention from clinicians regarding the possibility of pancreatitis. Once pancreatitis is detected, the primary disease needs active treatment for better prognosis.

Backgroud To summarize the clinical characteristics and identify the risk factors for pediatric Takayasu arteritis (TAK) with coronary artery lesions (CALs). Methods Clinical data of pediatric TAK patients in our center were retrospectively assessed. Independent risk factors for CALs were identified using multivariate logistic regression analysis. Survival analysis was used to compare differences in survival rates between the groups. Results Among the 66 pediatric TAK cases, the incidence of accompanying CALs was 39.4%. In the CAL group, 19 (73.1%) cases started within 36 months. None of the patients had symptoms of angina or ischemia on electrocardiogram (ECG), the CALs were detected using coronary ultrasound. The CALs most commonly were the left main and right coronary arteries. The lesions were mostly small or middle coronary artery aneurysms; some children may have giant coronary aneurysmal dilations, thrombosis and heart failure. The age of onset and symptom onset to diagnosis in TAK patients with CAL were lower than those in TAK patients without CAL(P < 0.005). TAK patients with CAL had significantly higher CRP,WBC, PLT,TNF-α and IL-2R levels (P < 0.05), lower HGB (P = 0.01), lower rate of renal artery stenosis (RAS) (P = 0.009). In multivariate logistic regression, the risk factors for pediatric TAK combined with CAL included the age of TAK onset (OR = 0.9835, 95% CI: 0.9710–0.9946, P = 0.006) and RAS (OR = 0.1901, 95% CI: 0.0386–0.7503, P = 0.03). In addition, there was no significant difference in survival rates between the two groups after regular treatment. Conclusion This study showed that the occurrence of CAL in pediatric TAK patients has a relatively more rapid clinical course, and a stronger inflammatory state at the time of diagnosis. The earlier the age of TAK onset and without RAS are more likely to cause CAL.

Background Lupus mesenteric vasculitis (LMV) as initial presentation is rare, especially in childhood-onset systemic lupus erythematosus (cSLE). It is a critical complication of lupus. At present, the research on cSLE with LMV as the initial presentation is few. The aim of this study was to analyze the clinical characteristics and prognosis of cSLE with LMV in the Chinese population, compared with non-LMV cSLE. Methods A retrospective case-controlled study was conducted on 55 cSLE patients between July 2018 and July 2021. The clinical data, laboratory findings, imaging, treatment, and follow-up data were collected and compared between the two groups of cSLE with LMV and non-LMV. Non-LMV cSLE patients were matched according to the age and sex of LMV patients. Results A total of 11 cSLE patients with LMV as the LMV group and 44 cSLE patients without LMV as the non-LMV group were included. The average age of onset was 12.55 ± 1.57 years old, the male-to-female ratio was 2:9, and high disease activity was observed in the LMV group. Abdominal pain was most common in LMV. Compared with the non-LMV, the percentage of abdominal pain, vomiting, abdominal distension, and diarrhea was higher, and gastrointestinal tract, serous cavity, kidney, and lung damage were higher in the LMV group ( P < 0.05). In abdominal-enhanced CT, the percentage of intestinal wall thickening, peritoneal effusion, mesenteric vascular enhancement, hydronephrosis with ureteral dilatation, intestinal congestion, and gastric mucosa thickening in the LMV group were higher than those in the non-LMV group ( P < 0.05). The percentage of receiving methylprednisolone pulse combined with cyclophosphamide pulse therapy in LMV was higher than in non-LMV. The clinical symptoms disappeared quickly, and there were no deaths in the LMV group. Compared with the non-LMV group, the 24-h urinary protein was higher, the complement C3 was lower, and the disease activity was higher in the LMV group ( P < 0.05). Conclusions LMV often occurs in 12 ~ 13-year-old girls with high disease activity of cSLE. Abdominal pain is the most common and more susceptible to damage to the kidney, serous cavity, and lung in cSLE with LMV. Methylprednisolone pulse combined with CTX pulse therapy is effective. After the treatment above, cSLE with LMV has a good prognosis, but the overall recovery is worse than non-LMV patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations and the pathogenesis of SLE is still unclear. Various omics results have been reported for SLE, but the molecular hallmarks of SLE, especially in patients with different disease activity, using an integrated multi-omics approach have not been fully investigated. Here, we collected blood samples from 10 healthy controls (HCs) and 40 SLE patients with different clinical activity including inactive (IA), low activity (LA), and high activity (HA). Using an integrative analysis of proteomic, metabolomic and lipidomic profiles, we report the multi-omics landscape for SLE. The molecular changes suggest that both the complement system and the inflammatory response were activated in SLEs and were associated with disease activity. Additionally, activation of the immunoglobulin mediated immune response were observed in the LA stage of the disease, however this immune response was suppressed slightly in the HA stage. Finally, an imbalance in lipid metabolism, especially in sphingolipid metabolism, accompanied with dysregulated apolipoproteins were observed to contribute to the disease activity of SLE. The multi-omics data presented in this study and the characterization of peripheral blood from SLE patients may thus help provide important clues regarding the pathogenesis of SLE.

Biallelic pathogenic variants in NDUFS8, a nuclear gene encoding a subunit of mitochondrial complex I, result in a mitochondrial disorder characterized by varying clinical presentations and severity. Here, we expand the neuroimaging and clinical spectrum of NDUFS8-related disorder. We present three cases from two unrelated families (a girl and two brothers) homozygous for a recurrent pathogenic NDUFS8 variant [c.460G>A, p.(Gly154Ser)], located in the [4Fe-4S] domain of the protein. One of the patients developed auto-antibody positive diabetic ketoacidosis. Brain MRIs performed in two of the three patients demonstrated diffuse cerebral and cerebellar white matter involvement including corticospinal tracts, but notably had sparing of deep gray matter structures. Our report expands the neuroimaging phenotype of NDUFS8-related disorder to include progressive leukodystrophy with increasing brainstem and cerebellar involvement, with relative sparing of the basal ganglia. In addition, we describe autoimmune diabetes in association with NDUFS8-related disorder, though the exact mechanism of this association is unclear. This paper provides a comprehensive review of case presentation and progressive neuroimaging findings of three patients from two unrelated families that have an identical pathogenic NDUFS8 variant, which expands the clinical spectrum of NDUFS8-associated neurological disease.

INTRODUCTION:The aim of this study was to assess the differences between childhood-onset and adult-onset systemic lupus erythematosus (cSLE and aSLE) for clinical manifestations and mortality using a meta-analytic approach.METHODS:The PubMed, EMBASE, and the Cochrane library were searched for eligible studies published between January 1982 and March 2021. The odds ratio (OR) with 95% confidence interval was used to calculate the pooled effect estimates using the random-effects model.RESULTS:Thirty-four studies involving 21,946 SLE patients were included. cSLE was associated with an increased risk of malar rash (OR: 1.64; p < 0.001), ulcers/mucocutaneous involvement (OR: 1.22; p = 0.039), general neurological involvement (OR: 1.52; p < 0.001), seizures (OR: 1.92; p < 0.001), general renal involvement (OR: 2.08; p < 0.001), proteinuria (OR: 1.35; p = 0.015), urinary cellular casts (OR: 1.67; p = 0.047), fever (OR: 2.31; p < 0.001), anemia (OR: 1.91; p < 0.001), thrombocytopenia (OR: 1.41; p < 0.001), leucopenia (OR: 1.57; p = 0.017), lymphadenopathy (OR: 2.40; p < 0.001), and cutaneous vasculitis (OR: 1.72; p = 0.001) as compared with aSLE. Moreover, cSLE versus aSLE was associated with a reduced risk of articular manifestations (OR: 0.63; p = 0.001), pulmonary involvement (OR: 0.54; p = 0.001), and pleuritis (OR: 0.61; p < 0.001). There were no significant differences between cSLE and aSLE for mortality risk (OR: 1.20; p = 0.203).CONCLUSION:We found that certain clinical manifestations of SLE are different in cSLE and aSLE. Moreover, the mortality risk of cSLE and aSLE was not significantly different.

Background There is insufficient evidence on the clinical effectiveness and safety of infliximab (IFX) treatment of Takayasu arteritis (TA) in infants. Methods We evaluated the therapeutic effectiveness and safety of IFX in a retrospective case series of 10 infantile TA patients. Observations included assessment of clinical symptoms, laboratory testing, and vascular imaging. Results Fever was the presenting symptom for 8 of 10 infants with TA. During acute episodes, leucocyte and inflammatory indices were significantly increased. Vascular imaging showed the most commonly involved arteries to be carotid arteries, abdominal aortas, and coronary arteries (9 cases, 90%). Two weeks after initiating IFX treatment, leukocyte and platelet counts decreased and hemoglobin levels increased. There were statistically significant clinical improvements 6 weeks after starting treatment compared with before treatment (p < 0.05). Inflammatory indices decreased 2 weeks after starting IFX treatment compared with before treatment (p < 0.05). Vascular lesions began to recover within 1.5-3 months of initiating IFX therapy, and involved vessels significantly recovered within 13 months. Some arteries remained stenotic, with intimal thickening and uneven lumen wall thicknesses. The only adverse event was a treatment-responsive allergic reaction during IFX infusion in one infant. Conclusions Fever was the main manifestation of illness and was often accompanied by significantly increased inflammatory indices. IFX treatment was apparently effective and reduced or eliminated need for glucocorticoids. IFX had a reasonably good safety profile.

OBJECTIVES Endothelial nitric oxide synthase (eNOS) is a type of nitric oxide synthase that mainly exists in the endothelium. It produces nitric oxide (NO) to regulate the function of endothelial cells. Endothelial dysfunction and increased NO metabolites have been shown in animal models of lupus and in lupus patients, so eNOS gene polymorphisms may be important in the pathogenesis of SLE. This study aimed to investigate the association of the single nucleotide polymorphisms (SNPs) of eNOS and paediatric systemic lupus erythematosus (pSLE). METHODS A total of 91 pSLE cases and 90 healthy controls were used in this study. We divided these patients into 4 subgroups according to kidney or central nervous system involvement. Four selected SNPs in the gene were analysed with MALDI-TOF mass spectrometry. Statistical methods were carried out to investigate the correlation between the SNPs and pSLE. RESULTS SNP rs1808593 genotype GT in case group were significantly higher than those in the control group (p=0.047), and the genotype GT had positive correlation with pSLE (OR=1.93, 95% CI: 1.01-3.69). In subgroup C (the patients with central nervous system but no kidney damage), the genotype GT was significantly higher than those in the control group (p=0.028), and the genotype GT was related to pSLE with central nervous system damage (OR=6.24, 95% CI: 1.17-33.15). In male patients, we found SNP rs1808593 genotype GT in pSLE group was significantly higher than in the control group (p=0.0065), and the risk of pSLE increased in patients with genotype GT (OR=8.36, 95% CI: 2.02-34.6). CONCLUSIONS SNP rs1808593 GT genotype is significantly higher than that in the control group, which may indicate that this genotype increases the risk of pSLE, especially in boys, and also this genotype might increase the risk of central nervous system involvement. Therefore, eNOS gene SNP rs1808593 genotype may have an important role in predicting the occurrence of pSLE and central nervous system complications in pSLE.