Pediatric rheumatic diseases are a group of complex chronic inflammatory disorders， mainly including juvenile idiopathic arthritis， diffuse connective tissue diseases， systemic vasculitis， and autoinflammatory diseases. Liver involvement is quite common in pediatric rheumatic diseases. In most cases， pediatric rheumatic diseases with liver involvement manifest as varying degrees of abnormal liver enzymes or hepatomegaly and may not have significant liver parenchyma lesions， and such diseases rarely progress to liver decompensation. Only a few children with rheumatic diseases may develop severe liver lesions. Liver involvement in children with rheumatic diseases may be caused by the primary disease itself or concurrent autoimmune liver diseases， but secondary factors are more common， including drug-induced liver damage caused by drugs used to treat rheumatic diseases， viral hepatitis， and fatty liver disease. This article summarizes liver involvement in pediatric rheumatic diseases， in order to provide a reference for the etiological analysis， diagnosis， and treatment strategies of liver involvement in pediatric rheumatic diseases.

Signal transduction and activator of transcription factor 1(STAT1), one of the important members of the STAT family, is a key cytoplasmic transcription factor and an important component of the JAK-STAT signaling pathway. Gain-of-function mutations in STAT1 (STAT1-GOF) impaired the dephosphorylation of STAT1 protein, mediated the enhancement of cell signaling pathways such as type Ⅰ, Ⅱ, and Ⅲ interferon(IFN) and interleukins-27 (IL-27), IL-6, IL-10, and IL-17, and inhibited Th17 cells. The clinical manifestations of STAT1-GOF are diverse, including chronic mucocutaneous candidiasis and autoimmune diseases. For the treatment of STAT1-GOF, such as targeted therapy with ruxolitinib for STAT1 hyperphosphorylation, immunomodulatory therapy and hematopoietic stem cell transplantation for different self-immune systems, certain curative effects can be obtained. With the understanding of disease mechanisms and the discovery of new clinical phenotypes, this review focuses on the diseases caused by gain-of-function mutations of STAT1, and introduces the clinical manifestations and treatment progress of STAT1-GOF to promote the understanding of such diseases and their future diagnosis, treatment and research works.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

Objective:To analyze the vaccination recommendations and follow-up for children with special health status.Methods:In this retrospective cohort study, 509 children who attended the Consultation Clinic of Vaccination for Special Health Children in Beijing Children′s Hospital from August 2020 to February 2023 were selected, the children were given vaccination planning advice after the assessment. The clinical data were collected, including the general situation, special health conditions, vaccination recommendations and implementation status, occurrence and outcomes of suspected adverse events following immunization (AEFI) after vaccination. The vaccination situation and safety in these children were evaluated.Results:Among the 509 children, the most common special health conditions were cardiovascular system diseases (103 cases), followed by neurological diseases (88 cases) and neonatal problems (82 cases). After comprehensive evaluation and multidisciplinary collaboration, 399 children (78.4%) were recommended to receive vaccination/catch-up vaccination according to the immunization program, 63 children (12.4%) were recommended to receive some vaccines but temporarily suspend others, and 47 children (9.2%) were recommended to temporarily suspend vaccination. A total of 449 children (88.2%) were actually vaccinated, AEFI occurred in 49 children and 45 cases were considered as general reactions.Conclusions:The majority of children with special health status can be vaccinated, and the overall compliance and safety are high. The individualized immunization evaluation model of multidisciplinary collaboration is conducive to the completion of the immunization program of children with special health status.

The clinical data of a child with ABCB1 rs1045642 T/T genotype and skin photosensitivity induced by Voriconazole were analyzed retrospectively in Beijing Children′s Hospital, Capital Medical University in September 2020.Literature was reviewed to discuss the relationship between ABCB1 genetic polymorphism and Voriconazole pharmacokinetics.The patient was a 6.8-year-old boy, who was diagnosed with primary immunodeficiency disease.Long-term oral Voriconazole was administered for prevention and treatment of fungal infections.Skin photodistributed erythema and pigmentation occurred about 3-4 weeks after treatment.The skin lesions were significantly alleviated about 1 month after the withdrawal of Voriconazole.Gene test showed ABCB1 rs1045642 T/T in the patient.Some studies reported that ABCB1 rs1045642 T/T genotype reduced the clearance rate of Voriconazole.Monitoring such adverse reaction of Voriconazole in clinical practice is important. ABCB1 gene polymorphism is possible to correlate with the pharmacokinetics and adverse reactions of Voriconazole.However, further large-scale clinical studies are warranted to verify it.

The Nod-like receptor family pyrin domain-containing protein 12(NLRP12), a newly discovered member of the Nod-like receptor family, is one of the important pattern recognition receptors.It recognizes a variety of pathogens, initiates downstream immune responses, and participates in the regulation of multiple inflammatory responses.NLRP12 is related to the occurrence and progression of inflammatory diseases.In this review, the structure and function of NLRP12 as well as NLRP12-associated autoinflammatory diseases were discussed, so as to provide new insights for the understanding, exploration and treatment of NLRP12-associated autoinflammatory diseases.

Precision medicine aims at using target therapy on specific diseases by studying the pathogenesis and finding biomarkers. Inborn errors of immunity (IEI) are caused by single gene mutations, providing the perfect human models to study immunology. The technology rapidly developes recently, so scientists have a deeper understandings of the phenotypes, genotypes, and the biological targets, so that doctors are able to use precision medicine on IEIs with many successful cases. The precision medicine have advantages in the treatment of pathogenesis of diseases. This article summarizes successful cases of using precision medicine for IEI recently.

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency characterized by severe bacterial and fungal infections and tissue granuloma formation early in life. Diagnosis of CGD involves the granulocyte function assays and gene mutation analysis. X-linked CGD (XL-CGD) caused by gene defects of CYBB is the most prevalent type of CGD. The clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD were reported here. The patient is a 7-year-old boy manifested as recurrent lower respiratory tract infection and failed to thrive. The patient had a history of osteo- myelitis and perianal abscess, with Bacille Calmette-Guérin (BCG) vaccine complications. Respiratory burst of neutrophils was measured with DHR oxidation assay and the histogram showing no significant change in neutrophil fluorescence after stimulation of the patient and the mother's histogram had a pattern of 2 peaks after stimulation. A heterozygous mutation in the CYBB gene (c.866G > A, p.W289X) was identified through inheritance from the patient's mother. Genetic analysis from blood and cheek mucosal cells indicated the female was a mosaicism in CYBB with mutation was present in about 19.5% of her leukocytes. We reported the clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD for the first time in China to enrich the understanding of XL-CGD and provide new sights for the hereditary counseling.

Objective:To summarize the clinical characteristics, common images, pathogens, and gene mutation types of chronic granulomatosis disease (CGD) in 19 children.Methods:The clinical manifestations, laboratory findings, treatment, and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results:The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases), and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection (19/19 cases), Bacillus Calmette Guerin (BCG)-osis (14/19 cases), lymphadenitis (14/19 cases), perianal abscess (9/19 cases), skin abscess (5/19 cases) and ulcerative colitis (2/19 cases). There were 59 positive cultures.Pathogens included fungi (9 cases), Klebsiella pneumonia (8 cases), mycobacteria (7 cases), Streptococcus Viridans (5 cases), Escherichia coli (3 cases), gram-positive bacteria (3 cases), Staphylococcus aureus (3 cases), and Burkholderia cenocepacia (2 cases). Gene mutations were found in all 19 patients, including 17 cases of CYBB, 1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations (6 cases), deletion mutations (5 cases, including 2 large fragment deletions), splice mutations (3 cases) and missense mutations (5 cases). Five mutations were novel.Splice mutations in 3 cases often led to skin abscess, perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients. Conclusions:In China, CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD, and fungi are dominant pathogens of CGD.The most common infection is respiratory infection. Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.

Currently, there are many reports on the clinical phenotypes and epidemiological data of COVID-19. Understanding the underlying pathogenesis is important for disease management. With the implications from studies on severe acute respiratory syndrome (SARS), this review mainly discussed the pathogenesis of COVID-19 and focused on the host immune response to viruses. Direct damage to tissues and organs and excessive inflammatory responses induced by 2019-nCoV are associated with the pathological process and disease progression. Viral load and high inflammatory response are related to disease severity. Peripheral lymphocytes are closely associated with the acute lung injury, and can be used to predict disease severity. 2019-nCoV-specific antibody and T cell immune response can be detected in patients with 2019-nCoV infection. Given the two sides of inflammation and hormone therapy, steroid as a broad-spectrum immunosuppressant needs to be used with caution. Biologics targeting IL-6 and convalescent plasma therapy are promising treatment for COVID-19. Further research on viral features, pathogenesis, immunopathogenesis and specific immune defense would be conducive to better understanding of COVID-19 and achieving precision medicine.