Natural killer(NK) cells are large granular lymphocytes differentiated from lymphoid progenitor cells, which play an important role in antiviral and anti-tumor by exerting cytotoxic function and producing cytokines.The alteration or imbalance of function of NK cells is closely related to the occurrence of autoimmune diseases.However, the role of NK cells in autoimmune diseases is rarely reported.In addition, as a bridge between innate and adaptive immunity, the role of NK cells in inflammation and immune regulation is also worth further investigation.This paper reviews the available studies on NK cells in rheumatoid arthritis, Henoch-Sch?nlein purpura, and systemic lupus erythematosus, in order to deepen the understanding and enhance the exploration of the relationship between NK cells, T and B lymphocytes, and the role of NK cells in the pathogenesis of autoimmune diseases.

Juvenile idiopathic arthritis(JIA)is a common chronic rheumatic disease in childhood.It is not a single disease, but a group of heterogeneous diseases including different subtypes.The etiology and pathogenesis of JIA are still unclear.It is currently believed that immune response disorders play an important role in its pathogenesis and development.Different subgroups of adaptive immune cells(including T lymphocytes and B lymphocytes, etc.)may participate in the pathogenesis of different subtypes of JIA, leading to different clinical manifestations.However, the specific mechanism of action and related molecular signaling pathways have not been fully elucidated.This paper reviews the latest research results in recent years and explores the role of different types of adaptive immune cells in the development of various subtypes of JIA, which will help the precise diagnosis and individualized treatment of each subtype of JIA.

The clinical features and genetic variants of the patient with sitosterolemia who was referred to Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine from June 2019 to January 2020 were retrospectively analyzed.The patient was treated with Ezetimibe tablets combined with diet control, and the follow-up was performed regularly.Besides, a relevant literature review was conducted.A 7-year and 5-month-old boy was referred to the hospital for " repeated thrombocytopenia for 7 months" with normal serum cholesterol.The whole exome sequencing showed that compound heterozygous mutations (p.Arg446*, p.Gln251*) in ABCG5 gene were inherited from their parents respectively.Hence, he was diagnosed with sitosterolemia.After 29 days of treatment with Ezetimibe tablets combined with diet control, the patient′s platelets returned to normal values without obvious adverse reactions related to drugs.Children with sitosterolemia may present with rare thrombocytopenia, and the therapeutic effects of Ezetimibe tablets combined with diet control are favorable.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To analyze the clinical characteristics of children diagnosed with systemic lupus erythematosus(SLE)complicated with thrombotic microangiopathy(TMA)for early recognition.Methods:We retrospectively reviewed the clinical records of 14 SLE patients with TMA hospitalized at Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine from December 2005 to October 2020.Results:The incidence of TMA was 5.65%(14/248)of the hospitalized patients with SLE and 7.87%(14/178)of the hospitalized patients with lupus nephritis.Four patients were boys while ten patients were girls.One boy was six years old and other 13 patients were from 11 to 18 years old.Their SLEDAI scores ranged from 14 to 31, and all of them were severe activity.Renal biopsy of 11 patients during TMA course all revealed lupus nephritis(type Ⅳ, n=8; type Ⅳ+ Ⅴ, n=3). These 14 SLE children were diagnosed with TMA within 3 days to 2 months after admission.At the beginning of the hospitalization, only six patients had both anemia and thrombocytopenia, while eight patients only had moderate anemia.All of the patients had obvious hypocomplementemia.Especially in the patients with first onset of SLE without treatment, their serum levels of C3 were less than 0.17 g/L and C4 were less than 0.07 g/L.Moreover, glomerular filtration rates of these patients were lower than that in normal range.The follow-up time were 0.2-11.3 years(median time was 2.6 years). After treatment, six patients obtained complete remission, and five patients obtained partial remission.One patient had sudden death during the 4th plasmapheresis, and the other two patients deteriorated. Conclusion:Children with SLE and TMA are mostly in severe disease activity, and renal pathology is type Ⅳ lupus nephritis.The SLE children with anemia should be paid special attention to the level of serum complement whether they have thrombocytopenia or not.If the level of serum complements decrease obviously, glomerular filtration rates should be monitored closely and schistocytes should be searched repeatedly in the blood smears of the peripheral blood to facilitate the early recognition of TMA.

There is a wide spectrum of rheumatic diseases which manifest in children′s connective tissue disease(CTD). Lung involvement is common within the spectrum of CTD.And interstitial lung disease (ILD) is among the most serious complications.The early diagnosis and treatment is vital to improve the prognosis.In this article, the mechanisms, subtypes, clinical manifestations and management of children′s CTD-ILD are reviewed.

Objective:To elucidate the clinical features of connective tissue disease associated interstitial lung disease (CTD-ILD) in children.Methods:A total of 24 children diagnosed with CTD-ILD and treated in Department of Rheumatology and Immunology, Shanghai Children′s Medical Center from January 2010 to December 2019 were included in the study. Their medical data including clinical features, lab test, imaging, pulmonary function test, treatment and outcome were analyzed statistically.Results:In these 24 patients, 4 were males and 20 females. Their main clinical presentations were cough (10/24, 42%), shortness of breath (10/24, 42%), tachycardia in quiet state (8/24, 33%), fatigue with activity (7/24, 29%), and fever (6/24, 25%). The main abnormal physical examination findings were moist rales (4/24, 17%) and acropachy (2/24, 8%). There were various abnormal findings in the patients′ lab test. All the patients (100%) had pulmonary interstitial changes on chest CT. Eight patients had spirometry test, and all (100%) showed decreased diffusion capacity. After immunosuppressive treatment, 15 cases (63%) improved, 4 cases (17%) gave up or died, while 5 cases (21%) had no significant improvement on the imaging examination.Conclusions:The onset of pediatric CTD-ILD could be insidious. Early diagnosis and aggressive treatment may change the prognosis, but are both difficult and need further studies.

In order to improve the quality and yield of Gastrodia elata f. glauca,determine the suitable Armillaria strains for the accompanying experiment in Xiaocaoba,Yiliang,four Armillaria strains were selected. They were used for G. elata cultivation,and the gene sequence,r DNA-ITS,β-tubulin and EF1-α of four Armillaria strains,were compared and analyzed. The yield was mesured in November which was based on previous laboratory research. The tubers were washed and steamed,then dried and powdered. The content of gastrodin and p-hydroxybenzyl alcohol was determined by UPLC,the polysaccharide was determined by phenol-concentrated sulfuric acid method. The results showed that the strains M1,M2,M3 and M4 were Armillaria gallica group but there were differences in the yield and active ingredient content when they were cultivated with the same G. elata. The yield of G. elata( Jian Ma) was the lowest when cultivated with Armillaria strain M3,but it was not the same when used M1,0. 981 kg·m-2,the highest yield in the four stains.The content of gastrodin was 0. 581%,the total content of gastrodin and p-hydroxybenzyl alcohol was 0. 595%,when accompanied with M1 strains. It was higher than other strains. The content of G. elata polysaccharide was 2. 132%,which was similar to the content of M3 strain,higher than that of M2 and M4 strain. Selecting phylogenesis of Armillaria strians,the content of active ingredient,and the yield as indicators,it was concluded concerned that the M1 strain was the best of four strains. The results will provide a theoretical basis and guidance for higher yield and quality in cultivation of G. elata in Yiliang.
Armillaria/physiology* ; Gastrodia/microbiology* ; Phylogeny ; Plant Tubers/chemistry* ; Plants, Medicinal/microbiology*

Objective To study the clinical characteristics of neonatal macrophage activation syndrome (MAS) associated with maternal rheumatic diseases and improve the understanding of neonatal MAS.Method Clinical data of MAS in a newborn infant with adult-onset Still's disease (AOSD) mother was retrospectively studied.From the establishment day of databases (CNKI,VIP,Wanfang,Pubmed and Embase) to December 2017,literature were retrieved with key words including "newborn","macrophage activation syndrome" and "hemophagocytic lymphohistiocytosis (HLH) ".Clinical features of infant MAS/HLH with maternal rheumatic diseases were summarized.Result A 27-day-old boy with AOSD mother manifested with fever,watery stools,irritability,prominent enlargement of right parotid gland and right cervical lymphadenitis.The infant was diagnosed with MAS due to coagulopathy,multiple organ dysfunction,hypofibrinogenemia and increased levels of ferritin.Anti-SSA/Ro52kD and stool rotavims antigen were positive.The infant recovered with intravenous immunoglobulin and steroids therapy.Follow-up at 2-year-old were normal.A total of 3 other cases of neonatal MAS/HLH were retrieved.All patients had high fever,hepatosplenomegaly and multiple organ dysfunction,impaired digestive system (abdominal distention,diarrhea and ascites),disseminated intravascular coagulation (2 cases),mental disorders (1 case),complete atrioventricular block (1 case) and severe hypotension (1 case).Laboratory results showed thrombocytopenia,elevated level of hepatic enzyme and serum ferritin in all patients.Targeted panel-based next generation sequencing were all negative for pathogenic gene mutations.After treatments of steroids,intravenous immunoglobulin and chemotherapy,all patients improved and ultimately cured.Conclusion In view of the impacts of the maternal rheumatic diseases on fetus,newborns with early onset high fever and hepatosplenomegaly should be suspected of MAS.Early diagnosis and effective treatment are crucial for clinical improvement.

Objective To explore the diagnosis and treatment of childhood primary Sjogren syndrome (pSS) with central nervous system symptoms as the first manifestation. Methods The clinical data of an 11-year-old male with pSS which had onset with fever and headache was retrospectively analyzed. The related literatures were reviewed. Results The subject was diagnosed with pSS by autoantibody detection, lip biopsy, and ophthalmologic examination. The symptoms were improved after immunosuppressive therapy. According to the literature, the incidence of childhood pSS was low, in which the incidence with involvment of the nervous system as primanry manifestation was even lower, and headache is the most common symptom of central nervous system. The application of corticosteroids and immunosuppressants may help improve the conditions. Conclusions Involvement of central nervous system in childhood pSS is not typical. Detection of autoantibodies and lip biopsy are helpful for diagnosis.