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Objective To find indicators of disease severity and factors of early remission in patients with deficiency of adenosine deaminase 2 (DADA2). Methods We enrolled six DADA2 patients from six families. Direct sequencing of adenosine deaminase 2 gene (ADA2) was performed by Sanger analysis. A literature review was conducted for articles regarding paediatric DADA2. Results We found that more organs were involved in early-onset (≤1 year of age) than in late-onset (>1 year of age) DADA2 patients had high level inflammatory responses, such as elevated ESR, SF, serum amyloid A and CRP. Disease severity was not significantly different from missense and frameshift mutation. Early administration of TNF inhibitor might result in better remission and reduce recurrence. In the literature, four articles describing 51 paediatric DADA2 patients were identified. We also found that fever, stroke, peripheral nervous system involvement, hypogammaglobulinaemia and hypertension were more frequent in early onset DADA2 patients. Conclusion Early-onset DADA2 may be more severe. Early administration of TNF inhibitor can effectively reduce recurrence and quickly alleviate the disease.

Juvenile dermatomyositis (JDM) is an autoimmune disease characterised by a great heterogeneity in its clinical manifestations. In this study, we aimed to investigate the association between different clinical subtypes, laboratory data, and myositis antibodies of JDM.A total of 132 JDM patients were enrolled and their medical records were retrospectively reviewed and autoantibodies tested. Twenty-one variables, including clinical manifestations and laboratory findings, were selected for analysis. We selected principal component analysis (PCA) as a pre-processing method for cluster analysis to convert the 21 original variables into independent principal components. We then conducted a PCA-based cluster analysis in order to analyse the association between patient clusters and the clinical data, laboratory data, and myositis autoantibodies.We identified 4 distinct JDM subgroups by PCA-based cluster analysis, namely: cluster A, JDM patients with arthralgia and intense inflammation; cluster B, JDM patients with clinical manifestations of vasculitis; cluster C, hypermyopathic JDM patients; and cluster D, JDM patients with skin involvement. There were significant differences between the 4 groups in serum alkaline phosphatase levels, usage of aggressive immunosuppressive therapy, and autoantibody expression of anti-mi2, anti-MDA5, anti-Jo1, and anti-PM-Scl100.We conducted cluster analysis of a cohort of JDM patients and identified 4 subgroups that represented diverse characteristics in the distribution of laboratory data and myositis autoantibodies, indicating that multidimensional assessment of clinical manifestations is highly valuable and urgently needed in JDM patients. These subgroups may contribute to individualised treatments and improved JDM patient prognosis.

Cerebral venous sinus thrombosis (CVST) is a rare complication of childhood-onset SLE (cSLE) and is potentially fatal to the patient. In order to better define the characteristics of CVST in cSLE, we analysed a single-centre study of cSLE presenting with CVST.Clinical characteristics and laboratory findings of cSLE patients complicated with CVST from January 2006 to December 2019 were analysed through this retrospective, single-centre study.A total of 1395 records of cSLE patients were reviewed. Five patients (0.36%) had CVST. Headache (80%) was the most frequent symptom. The transverse sinus (45%) was the most frequent location of thrombus, followed by the sigmoid sinus (27%). The SLE disease activity index (SLEDAI) at the time of CVST was 11±3. The D-dimer was elevated in all 5 cases, only one patient was positive for ACL and anti-β2GP-I IgM. All the patients underwent MRV screen to confirm the diagnosis. All the patients had a favourable outcome after receiving glucocorticoid and immunosuppressant treatment, as well as anticoagulant therapy.CVST is relatively rare in cSLE and tends to occur in active lupus patients. Severe and persistent headache is an index of CVST. Early diagnosis and more intensive therapy for SLE, combined with anticoagulation therapy, could significantly improve the prognosis of CVST in cSLE.

Lupus nephritis is one of the most common and severe systemic lupus erythematosus complications. However, the pathogenesis of lupus nephritis is still poorly understood. Increasing evidence has shown that microRNAs (miRNAs) are extensively involved in the pathophysiology of autoimmune diseases. NZBWF1 is the classical mouse model of lupus nephritis. The present study aimed to investigate the expression profiling of mRNA and miRNAs of NZBWF1 mice with lupus nephritis using microarray, and explored the potential molecular mechanism of miRNA. miRNA and mRNA microarrays were performed to identify miRNA and mRNA expression changes between pre-diseased (8-week-old) NZBWF1 mice and diseased NZBWF1 mice with lupus nephritis (28-week-old). Quantitative polymerase chain reaction (qPCR) validated these results. The target of miRNA was confirmed through a dual-luciferase reporter and stimulated mesangial cells experiment. The combined miRNA and mRNA analysis identified 43 differentially expressed miRNAs and 1796 differentially expressed mRNAs between pre-disease (8-week-old) (n = 4) and diseased (28-week-old) NZBWF1 mice. We found that miR-1968-5p was significantly decreased, and csf1 mRNA was significantly increased in lupus nephritis mouse and verified by RT-PCR. csf1 has been demonstrated to play important roles in SLE. Bioinformatics analysis predicted that the csf1 was a potential target gene of miR-1968-5p. A dual-luciferase reporter assay confirmed the target binding. In cell experiments, overexpression or knockdown of miR resulted in a decrease or increase of csf1 expression, respectively. These results suggest that miR-1968-5p may be involved in the pathogenesis of lupus nephritis of NZBWF1 mice by targeting csf1.

Early-onset Systemic lupus erythematosus (SLE) is a heterogeneous disease with more variable symptoms than other types of SLE. It can begin as early as 12 months after birth, and the clinical process appears to be more severe. The common clinical manifestations of early-onset SLE are skin and mucosal lesions, renal involvement, central nervous system diseases and hematological system abnormalities. Although the disease is well described in the literature, diagnosis is often difficult due to its insidious onset, early onset, and atypical symptoms. Here, we present four cases of early-onset SLE. Next-generation sequencing were performed and detected mutations were confirmed by Sanger sequencing in all four cases. In addition, glucocorticoid, propyl, cyclophosphamide, and other drugs were significantly improved after treatment. Conclusion: To our knowledge, this is the first case study in China describing early-onset SLE. With the research progress and knowledge integration of basic disciplines such as genomics, epigenetics and immunology, the pathogenesis of early-onset SLE and other rheumatoid immune diseases will be revealed, which will bring more hope for the diagnosis and treatment of early-onset SLE.

In this study, we aimed to explore the expression of the Aicardi-Goutières syndrome (AGS) mutant gene SAMHD1 in paediatric-onset systemic lupus erythematosus (pSLE), its correlations with clinical and laboratory parameters, and the relationship between its expression and the type 1 interferon (IFN) signalling pathway.Peripheral blood from 98 pSLE patients and 44 gender and age-matched healthy individuals were examined. Gene expression levels of SAMDH1 and interferon-stimulated genes (ISGs; MxA, IRF3 and IRF7) were evaluated using real-time RT-PCR assays.SAMHD1 levels in pSLE patients were significantly increased compared to those in healthy donors (p0.001). SAMHD1 was associated with serum ferritin (r=0.221, p=0.042) in pSLE patients. SAMHD1 levels were significantly increased (p0.05) in pSLE patients with butterfly erythema, alopecia, and photosensitivity. SAMHD1 was positively correlated with MxA, IRF3 and IRF7 levels, indicating that SAMHD1 was associated with the type 1 IFN signalling pathway.SAMHD1 was significantly increased and correlated with MxA, IRF3 and IRF7 in pSLE patients.

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterised and presents partially differently from adults. A large cSLE cohort study is lacking in China. The present study aimed to determine the clinical characteristics in a large population of patients with cSLE, and compare with adult-onset SLE (aSLE) in an SLE cohort of China.The retrospective study included patients with cSLE diagnosed at the Beijing Children's hospital between July 2006 and October 2020. All patients met at least 4 of ACR classification criteria for SLE. In addition, data including demographic, clinical and serologic data were collected. Our data were compared with other cSLE cohorts and Chinese aSLE cohorts.A total of 1020 patients were included in this study, comprising 808 female and 212 male patients (female to male ratio, 3.8:1). The mean age at diagnosis of lupus was 11.1 years (range 1.0-17.2). It took on average 6 months (range 0.1-132) from first symptoms to cSLE diagnosis and over 12 months in 12% of patients. The most common primary manifestations at onset were rash (37.2%), fever (33.4%), nephropathy (14.2%) and arthritis (13.6%). The most common clinical manifestations were rash (67.9%) and fever (57.5%). 59.4% of patients had haematological involvement, 46.0% had lupus nephritis, 33.2% had arthritis. cSLE was more active and associated with more inflammation than aSLE patients.This study is a large single-centre study on cSLE from China and clarifies the clinical phenotype and autoantibody spectrum of cSLE. The clinical manifestations and autoantibody spectrum of cSLE are diverse, with regional and populational differences.

Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling heritable connective tissue disease that is difficult to treat. This study seeks to explore the clinical characteristics, clinical manifestations, treatment and prognosis of FOP to provide a clinical basis for its early diagnosis and treatment. Twenty-six children with FOP were retrospectively analyzed in terms of their onset, clinical manifestations, auxiliary examinations and treatment. Among the 26 cases, the youngest age of manifestation of mass was 8 days after birth, and the average age was 3 years and 2 months. The peak age was 2–5 years old. Inflammatory mass and toe-finger deformity are the main early clinical manifestations of the disease. These inflammatory masses often lead to hard osteogenic deposits that initially mainly involve the central axis, such as the neck (22/26, 84.6%), back (20/26, 76.9%), and head (13/26, 50%). Toe-finger deformity mainly manifests as symmetrical great toe deformity, or short and deformed thumb and little finger. The diagnosis of FOP requires typical clinical manifestations or ACVR1 gene detection. The main therapeutic drugs for FOP include glucocorticoids and non-steroidal anti-inflammatory drugs. Although not compliant with the recommended medical management of FOP, in our clinical practice children with uncontrollable illness could be treated using a variety of immunosuppressive agents in combination. FOP is a rare autosomal dominant heritable disease. The main clinical manifestations observed in this study were recurrent inflammatory mass and toe-finger deformity. If the diagnosis and treatment are not performed in a timely manner, serious complications are likely to affect the prognosis. Therefore, early diagnosis and active treatment should be performed.

Background Chronic active Epstein–Barr virus (CAEBV) infection is a type of lymphoproliferative disorder characterized by chronic or recurrent infectious mononucleosis (IM)-like symptoms, which can have less-frequent clinical presentations. The prognosis of CAEBV is poor, and hematopoietic stem cell transplantation (HSCT) has been shown to be the only potentially effective treatment. In this article, we present a special CAEBV case of a patient who had no typical IM-like symptoms at the early stage, but manifested with severe and progressive coronary artery aneurysm (CAA), abdominal aortic lesions, and severe uveitis. These manifestations were uncommon features and could only be blocked by HSCT. Case presentation A 4-year-old girl with no special medical history complained of decreased vision for 10 months and cough after physical activities for three months. The blurred vision grew rapidly worse within one month, until only light perception remained. She was diagnosed with uveitis and cataract, and received prednisone and ciclosporin A treatment. However, her vision did not improve. Physical examination showed slight hepatosplenomegaly. Ultrasonic cardiogram showed bilateral CAA (5.0 mm and 5.7 mm for inner diameters), and abdominal CT scan revealed a thickened aortic wall, as well as stenosis and dilation of the segmental abdominal aorta. Other significant findings were increased EBV-DNA (3.29 × 104 copies/mL) from peripheral blood, positive EBV antibodies (EBV-CA-IgG, EBV-EA-IgA, and EBV-NA-IgG), and positive EBV-encoded small RNAs found by bone marrow biopsy. Based on her clinical manifestations and evidence for EBV infection, we diagnosed CAEBV. She received allogeneic HSCT, and the cataract operation was performed after HSCT. EBV-DNA could not be detected in peripheral blood after HSCT. Her CAAs did not progress, and uveitis was well controlled. Her vision recovered gradually over the 3 years after HSCT. Conclusions We present a rare CAEBV case of a patient who suffered from uncommon and severe cardiovascular and ocular involvement that was relieved by HSCT. Therefore, early recognition and diagnosis of CAEBV are of vital importance to improve its prognosis. In summary, this atypical CAEBV case could help us recognize similar cases more easily, make the right diagnosis as early as possible, and deliver proper and timely treatment.

The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash (93.3%) with fever (100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever (100%), rash (93.3%) and myalgia (76%). Other clinical manifestations include arthritis (11 cases), lung involvement (seven cases), optical dysfunction (seven cases), nerve deafness (six cases), nervous system involvement (five cases), hepatomegaly, splenomegaly and lymphadenectasis (five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen (FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789A

The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified 10 missense mutations, out of which five were new: R334L, E383D, R471C, C495R and D512F. The rest of them, R334W, R334Q, G481D, M513T and R587C, have been reported previously. Among all the mutations, R334W, R334Q and C495R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.

Recently, it was reported that circular RNAs (circRNAs) play the crucial role in many physiological and biological processes and can be used as biomarkers. However, the information about circRNAs in children with systemic lupus erythematosus (SLE) is limited. The aim of this study is to determine the expression of circRNAs in children with SLE and investigate the significance of circRNA for diagnosing SLE. Microarray profile of circRNAs and mRNAs was performed for identifying the changes in expression of circRNAs and mRNAs between children with SLE and healthy children. Quantitative polymerase chain reaction (qPCR) was used to confirm the results. Spearman correlation test was performed to assess the correlation between circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value. A comparison between the children with SLE and healthy children revealed that 348 circRNAs and 1162 mRNAs were expressed differentially. The authors constructed a complex circRNA target network consisting of 307 matched circRNA-mRNA pairs for 124 differentially expressed circRNAs (74 circRNAs were upregulated, and 50 circRNAs were downregulated) and 142 differentially expressed mRNAs (83 mRNAs were upregulated, and 59 mRNAs were downregulated) by using gene co-expression network analysis. The competing for endogenous RNA (ceRNA) network includes 42 differentially expressed circRNAs, 41 differentially expressed mRNAs, and 71 predicted miRNAs. Among these SLE patients, we detected that the hsa_circ_0021372 and hsa_circ_0075699 levels are associated with C3 and C4 levels in children with SLE. The hsa_circ_0057762 level is positively associated with the SLEDAI-2K score. The ROC curves of circRNAs showed that the levels of hsa_circ_0057762 (AUC 0.804, 95% CI 0.607–1.0, P = 0.02) and hsa_circ_0003090 (AUC 0.848, 95% CI 0.688–1.0, P = 0.008) could differentiate the patients with SLE from the healthy controls. We firstly characterized the expression profiles of circRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insight into the mechanisms of SLE pathogenesis, and circRNAs may serve as useful biomarkers for SLE.

Long noncoding RNAs (lncRNAs) are reported to play crucial roles in several physiological and biological processes. However, knowledge of lncRNAs in children with systemic lupus erythematosus (cSLE) remains limited. We investigate lncRNA expression profiling of cSLE and explore the potential function of lncRNAs.LncRNA and mRNA microarrays were performed to identify changes in lncRNA and mRNA expression between children with SLE and paired healthy children. Quantitative polymerase chain reaction (qPCR) validated these results. A Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the potential lncRNA function.A comparison between children with SLE and paired healthy children revealed that 1042 lncRNAs and 1162 mRNAs were differentially expressed. By using gene co-expression network analysis, we constructed a complex lncRNA target network consisting of 817 matched lncRNA-mRNA pairs for 309 differentially expressed lncRNAs and 210 differentially expressed mRNAs. The results of further GO and KEGG pathway analyses indicated that lncRNAs were involved mainly in pathways with crucial pathobiological relevance in SLE.We firstly characterised the expression profiles of lncRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insights into the mechanisms of SLE pathogenesis and may serve as diagnostic biomarkers for SLE therapy.