Delayed diagnosis of abdominal Henoch-Schonlein purpura in children:A case report

BACKGROUND For children with abdominal Henoch-Schonlein purpura presenting abdominal pain as an initial symptom and severe clinical manifestations,but without purpura appearance on the skin,the diagnosis and treatment are relatively difficult.This study summarized the characteristics of this group of patients by literature review and provided additional references for further refinement of glucocorticoid therapy in this vasculitis.CASE SUMMARY A 6-year-old girl presented mainly with repeated abdominal pain and had received short-term out-of-hospital treatment with hydrocortisone.On day 7 after onset,gastroscopy revealed chronic non-atrophic gastritis and erosive duodenitis without purpuric rash,and no obvious resolution of the abdominal pain was found after treatment against infection and for protection of gastric mucosa.On day 14 the inflammatory indices continued to rise and the pain was relieved after enhanced anti-infective therapy,but without complete resolution.On day 19,the patient presented with aggravated abdominal pain with purplish-red dots on the lower limbs,by which Henoch-Schonlein purpura was confirmed.After 5 d of sequential treatment with methylprednisolone and prednisone,abdominal pain disappeared and she was discharged.CONCLUSION Henoch-Schonlein purpura-related rash may appear after long-term abdominal pain,and should be distinguished from acute and chronic gastrointestinal diseases at the early stage without typical rash.For bacterial infection-induced Henoch-Schonlein purpura,glucocorticoid therapy alone without clearing the infection may not relieve symptoms.

Henoch-Schonlein purpura from vasculitis to intestinal perforation: A case report and literature review

Henoch-Sch?nlein purpura(HSP) is generally a selflimited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrastenhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications.

Regularity of syndrome differentiation and treatment of traditional Chinese medicine for Henoch-Schonlein purpura based on data mining techniques

Objective:This study aims to explore the regularity of syndrome differentiation and treatment of traditional Chinese medicine(TCM)for allergic purpura.Methods:CNKI,Weipu Chinese science and technology database,wanfang medical network database,and Chinese biomedical literature database were searched for eligible studies.Medical records including complete patient personal information,patient symptoms,TCM syndromes,treatment,and medication were included.The data was analyzed using the Chinese medicine heritage support platform provided by the Chinese Academy of Chinese medicine(V2.5).Results:Differentiation of health gas camp blood was the most commonly used method of differentiation of symptoms and signs in famous veteran TCM.The treatment included cooling blood,activating blood circulation,clearing heat and detoxifying toxins,removing blood stasis and stopping bleeding.Honeysuckle,Forsythia suspensa,cicada slough and other drugs were interrelated.Potential drug pair combinations and drug networks showed the basic drug composition of Qingying Decoction.According to the entropy cluster analysis,28 core drug combination and 12 new formulations were obtained.Conclusion:The regularity of syndrome differentiation and treatment of traditional Chinese medicine for Henoch-Schonlein purpura based on the famous and old TCM doctors was complex.Further researches are still needed.

Henoch-Schonlein purpura with intestinal perforation and cerebral hemorrhage: A case report

Henoch-Schonlein purpura (HSP) with intestinal perforation and cerebral hemorrhage is a very rare clinical condition. There has been no report of HSP complicated with both intestinal perforation and cerebral hemorrhage until October 2012. Here we describe a case of HSP with intestinal perforation and cerebral hemorrhage in a 5-year-old girl. Plain abdominal radiograph in the erect position showed heavy gas in the right subphrenic space with an elevated diaphragm. Partial resection of the small intestine was performed, and pathological analysis suggested chronic suppurative inflammation in all layers of the ileal wall and mesentery. Seventeen days after surgery, cerebral hemorrhage developed and the patient died.

Endoscopic findings in a patient with Henoch-Schonlein purpura

Hcnoch Schoenlein purpura (HSP) is a systemic vasculitis of the small vessels of the skin,joints,GI tract, and kidney.It preferentially affects children but may also occur in adults.We report a 60-rear-old man with HSP who presented with colicky abdominal pain,blondy diarrhea,arthralgia,and skin rash.The gastrointestinal tract was viewed by upper endoscopy and colonoscopy.We found characterislic endoscopic findings in the stomach,cecum and sigmoid colon,the combination of which has rarely been demonstrated in one patient.Histologic examination of skin biopsy specimens revealed leukocytoclastic vasculitis with positive staining for IgA in the capillaries.Endoscopy appears to have substantial diagnostic utility in patients suspected of having HSP,especially when abdominal symptoms precede the cutaneous lesions.

Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases

Henoch-Schonlein purpura(HSP) is a small vessel vasculitis mediated by type Ⅲ hypersensitivity with deposition of Ig A immune complex in the walls of vessels. It is a multi-system disorder characterizedby palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP.

Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

Helicobacter pylori(H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extraintestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura(HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum Ig A, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP.

Spectrum of Henoch-Schonlein Purpura in Children: A Single-Center Experience from Western Provence of Saudi Arabia

The aim of this study was to describe the common presentation, frequency, and complications of Henoch-Schonlein purpura (HSP) in patients <18 years who were followed up at King Abdulaziz University Hospital, Jeddah over the last 12 years. We performed a retrospective chart review of the medical records of all patients diagnosed as HSP. During this period, only 29 cases were reported (15 males, 14 females), with the mean age at the diagnosis 7.5 years. 82% percent of the patients had joint involvement in the form of arthritis or arthralgia;17.2% had no joint involvement. Abdominal manifestations were reported in 72.4% of the patients, while renal involvement was documented in 24.1% of the cases;two patients had scrotal involvement. Four patients (13.7%) had a recurrence within four months of HSP diagnosis. However, all patients had full recovery within a month. More research is warranted to study the prevalence, clinical manifestations, preceding factors, and complications of HSP in a Saudi-based cohort.

Effects of methylprednisolone combined with montelukast on immune function and cytokines in children with recurrent Henoch-Schonlein purpura

Objective:To study the effects of methylprednisolone combined with montelukast on immune function and cytokines in children with recurrent Henoch-Schonlein purpura.Methods:Children who were diagnosed with recurrent Henoch-Schonlein purpura in Zigong Third People's Hospital between September 2015 and August 2017 were selected as the research subjects and randomly divided into the intervention group who received methylprednisolone combined with montelukast therapy and the control group who received hydrocortisone therapy. The levels of Th1/Th2 and Th17/Treg immunity indexes in peripheral blood as well as cytokines in serum were measured before treatment as well as 4 and 8 weeks after treatment.Results: 4 weeks and 8 weeks after treatment, Th1 and Treg cell contents as well as T-bet and FoxP3 mRNA expression in peripheral blood of both groups of patients were significantly higher than those before treatment whereas Th2 and Th17 cell contents as well as GATA-3 and RORγt mRNA expression in peripheral blood and NF-κB, OPN, IL-33, MK and HMGB1 contents in serum were significantly lower than those before treatment, and Th1 and Treg cell contents as well as T-bet and FoxP3 mRNA expression in peripheral blood of intervention group were significantly higher than those of control group whereas Th2 and Th17 cell contents as well as GATA-3 and RORγt mRNA expression in peripheral blood and NF-κB, OPN, IL-33, MK and HMGB1 contents in serum were significantly lower than those of control group.Conclusion: methylprednisolone combined with montelukast treatment of recurrent Henoch-Schonlein purpura can regulate the immune function and inhibit the cytokine secretion.

Evaluation of the cytokine levels and immune response status of montelukast, loratadine and tanshinone combination therapy for Henoch-Schonlein purpura

Objective:To evaluate the cytokine levels and immune response status of montelukast, loratadine and tanshinone combination therapy for Henoch-Schonlein purpura.Methods: A total of 80 patients with Henoch-Schonlein purpura who were treated in Ankang Central Hospital between May 2014 and January 2017 were collected and divided into montelukast group, loratadine group, tanshinone group and combined treatment group according to the random number table, 20 cases in each group. Serum levels of inflammatory factors, Th17/Treg cellular immunity indexes before and after treatment were compared among four groups of patients.Results: Before treatment, differences in serum levels of inflammatory factors and Th17/Treg cellular immunity indexes were not statistically significant among four groups of patients. After treatment, serum HMGB1, IL-8, IL-14, IL-23 and IL-33 levels in combined treatment group were lower than those in montelukast group, loratadine group and tanshinone group;serum IL-17 level was lower than that in montelukast group, loratadine group and tanshinone group while IL-10 and TGF-β levels were higher than those in montelukast group, loratadine group and tanshinone group.Conclusions: Montelukast, loratadine and tanshinone combination therapy for Henoch-Schonlein purpura helps to reduce systemic inflammatory response and balance Th17/Treg cell immunity.

Overview of the pathogenesis of Henoch-Schonlein purpura in children and the research progress on related mechanism of inflammatory cytokines

Henoch-schonlein purpura (HSP) is a kind of systemic vasculitis that is common in childhood,and its pathogenesis is complicated and considered to have important relationship with lymphocytes, vascular endothelial cells and so on. The causes of this disease are complex and have not been clearly identified, but numerous studies have shown that inflammatory factors such as IL-1, IL-17 and TNF-α play an important role in the development of HSP.

A treatment for Henoch-Schonlein purpura based on Shaoyang Channels： a hypothesis and case report

过敏性紫癜是由IgA引起的血管炎,很容易复发.很多病人不得不使用糖皮质激素,免疫抑制药物,和其他药物来进行治疗,而这些药物会引起严重的副反应.不幸的是,在复发后大多数病人会出现腹部疼痛,关节炎,紫斑疹,及肾受累.在《伤寒论》中,小柴胡汤是治疗大多数腹痛和紫斑疹病人的著名药方.因此,在本案例中我们使用了小柴胡汤.此方入少阳经,有趣的是,我们发现这些症状病位在少阳经附近,所以这就是小柴胡汤可以起作用的原因.

Serum OPN and NF-κB contents in children with Henoch-Schonlein purpura and their correlation with oxidative stress and cellular immune function

Objective:To detect serum OPN and NF-κB contents in children with Henoch-Schonlein purpura (HSP) and study their correlation with oxidative stress and cellular immune function. Methods: The children who were diagnosed with HSP in Shijiazhuang First Hospital between February 2015 and October 2017 were selected as the HSP group of the study and the healthy children who received physical examination during the same period were selected as the control group. The serum was collected to measure the contents of OPN, NF-κB, oxidative stress indexes and immune cell inflammation, and the peripheral blood was collected to detect the mRNA expression of immune cell transcription factors.Results: OPN, NF-κB, MDA, MPO, IL-4, IL-5 and IL-17 contents in serum as well as GATA-3 and RORγt mRNA expression in peripheral blood of HSP group were significantly higher than those of control group whereas SOD, CAT, PON, IFN-γ and TGF-β1 contents in serum as well as T-bet and FoxP3 mRNA expression in peripheral blood were significantly lower than those of control group;serum OPN and NF-κB contents in HSP group were positively correlated with MDA, MPO, IL-4, IL-5 and IL-17 contents in serum as well as GATA-3 and RORγt mRNA expression in peripheral blood, and negatively correlated with SOD, CAT, PON, IFN-γand TGF-β1 contents in serum as well as T-bet and FoxP3 mRNA expression in peripheral blood. Conclusion: The abnormal increase of serum OPN and and NF-κB contents in children with HSP is closely related to the excessive oxidative stress activation and cellular immune dysfunction.

Effects of SOCS1 and SOCS3 in peripheral blood on CD4+T cell differentiation in children with Henoch-Schonlein purpura

Objective:To study the effects of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in peripheral blood on CD4+T cell differentiation in children with Henoch-Schonlein purpura. Methods: Children with Henoch-Schonlein purpura who were treated in Zigong Maternal and Child Health Hospital between June 2014 and February 2018 were selected as the HSP group of the study, and healthy children who received physical examination during the same period were selected as the control group of the study. Peripheral blood was collected to determine the expression of SOCS1 and SOCS3 as well as the contents of CD4+T cell subsets, and serum was collected to determine the contents of CD4+T cytokines.Results: SOCS1 and SOCS3 mRNA expression levels as well as SOCS3/SOCS1 ratio in peripheral blood of HSP group were significantly higher than those of control group;Th1 and Treg contents in peripheral blood as well as IFN-γ and TGF-β1 contents in serum of HSP group were lower than those of control group whereas Th2 and Th17 contents in peripheral blood as well as IL-4, IL-5 and IL-17 contents in serum were higher than those of control group, and Th1 and Treg contents in peripheral blood as well as IFN-γ and TGF-β1 contents in serum of HSP children with high SOCS3/SOCS1 ratio were lower than those of HSP children with low SOCS3/SOCS1 ratio whereas Th2 and Th17 contents in peripheral blood as well as IL-4, IL-5 and IL-17 contents in serum were higher than those of HSP children with low SOCS3/SOCS1 ratio.Conclusions: Changes in SOCS1 and SOCS3 expression in peripheral blood of children with Henoch-Schonlein purpura can affect the differentiation of CD4+T cells.

Severe Henoch-Schonlein purpura with infliximab forulcerative colitis

Infliximab （IFX） is an anti-tumor necrosis factorchimeric antibody that is effective for treatment ofautoimmune disorders such as Crohn＇s disease andulcerative colitis （UC）. IFX is well tolerated with alow incidence of adverse effects such as infections,skin reactions, autoimmunity, and malignancy.Dermatological manifestations can appear as infusionreaction, vasculitis, cutaneous infections, psoriasis,eczema, and skin cancer. Here, we present anunusual case of extensive and sporadic subcutaneousecchymosis in a 69-year-old woman with severe UC,partial colectomy and cecostomy, following her initialdose of IFX. The reaction occurred during infliximabinfusion, and withdrawal of IFX led to gradual alleviationof her symptoms. We concluded that Henoch-Sch？nleinpurpura, a kind of leukocytoclastic vasculitis, mighthave contributed to the development of the bruising.Although the precise mechanisms of the vasculitis arestill controversial, such a case highlights the importanceof subcutaneous adverse effects in the management ofUC with IFX.

Thrombotic Thrombocytopenic Purpura in Pregnancy Presented with Stroke at 29 Weeks: A Case Report

Thrombotic thrombocytopenic purpura (TTP) is a rare but acute, life-threatening condition which may be precipitated by pregnancy. This disorder that presents with thrombocytopenia, haemolytic anemia, and clinical consequences of microvascular thrombosis such as stroke. The exact cause is not known but it is associated with a deficiency of ADAMTS13 enzymes. Immune mediated TTP is more common and can present in pregnancy. The aim of this case is to bring awareness as many clinicians are unaware of this condition in pregnancy, its diagnosis may be missed or delayed, leading to fetal loss or serious maternal implications. In this case the patient presented at 29 weeks with stroke in Emergency department, referred to delivery suit for Obstetric review, with suspicion of Pre-eclampsia/HELLP. The diagnosis of TTP was achieved by a multidisciplinary team who worked tirelessly together. The patient was transferred to a Specialist Tertiary Care Centre for further management. The pregnancy continued until 33 weeks and 5 days. She underwent an emergency caesarean section for fetal distress. Steroids and Rituximab were continued postnatally. The outcome was favourable due to fast and efficient multidisciplinary care. Awareness of this rare but important condition can lead to recognition of clinical presentation, prompt diagnosis and appropriate management.

Role of p300 in the pathogenesis of Henoch-Schonlein purpura nephritis and as a new target of glucocorticoid therapy in mice

Background: Henoch-Schonlein purpura nephritis (HSPN) is a very common secondary kidney disease of childhood. Its pathogenesis and the treatment mechanism of glucocorticoid have not been fully elucidated. The aim of this study was to determine the relationship between p300 and the pathogenesis, glucocorticoid therapy in mice with HSPN, respectively. Methods: Forty-eight C57BL/6N male mice, weighing 18 to 20 g, were selected (3–4 weeks old, n = 8 per group). The mice in the normal control group (Group I) were given normal solvent and the HSPN model group (Group II) were given sensitizing drugs. The mice in Group III were injected intraperitoneally with dexamethasone after being given sensitizing drugs. Meanwhile, mice in Groups IV, V and VI with conditional knockout of p300 were also given normal solvent, sensitizing drugs and dexamethasone. The levels of serum IgA, creatinine, and circulating immune complex (CIC) concentrations, 24 h urinary protein and urinary erythrocyte in C57 wild mice, and p300 conditional knockout mice in each group were measured. The expression of p300 in renal tissues and the expression of glucocorticoid receptor (GR)α and β, transforming growth factor (TGF)-β1, and activator protein (AP)-1 after dexamethasone treatment were determined by real-time polymerase chain reaction and Western blotting. Results: Compared with the normal solvent control group (Group I), the expression of p300 mRNA in the model group (Group II) was significantly up-regulated. Western blotting further confirmed the result. Urinary erythrocyte count, 24 h urinary protein quantification, serum IgA, CIC, and renal pathologic score in Group V were distinctly decreased compared with non-knockout mice in Group II (9.7 ± 3.8 per high-power field [/HP] vs. 18.7 ± 6.2/HP, t = 1.828, P = 0.043;0.18 ± 0.06 g/24 h vs. 0.36 ± 0.08 g/24 h, t = 1.837, P = 0.042;18.78 ± 0.85 mg/mL vs. 38.46 ± 0.46 mg/mL, t = 1.925, P = 0.038;0.80 ± 0.27 μg/mL vs. 1.64 ± 0.47 μg/mL, t = 1.892, P = 0.041;7.0 ± 0.5 vs. 18.0 ± 0.5, t = 1.908, P = 0.039). Compared with non-knockout mice (Group III), the level of urinary erythrocyte count and serum IgA in knockout mice (Group VI) increased significantly after treatment with dexamethasone (3.7 ± 0.6/HP vs. 9.2 ± 3.5/HP, t = 2.186, P = 0.024;12.38 ± 0.26 mg/mL vs. 27.85 ± 0.65 mg/mL, t = 1.852, P = 0.041). The expression level of GRα was considerably increased in the knockout group after dexamethasone treatment compared with non-knockout mice in mRNA and protein level (t = 2.085, P = 0.026;t = 1.928, P = 0.035), but there was no statistically significant difference in the expression level of GRβ between condition knockout and non-knockout mice (t = 0.059, P = 0.087;t = 0.038, P = 1.12). Furthermore, the expression levels of glucocorticoid resistance genes (AP-1 and TGF-β1) were notably increased after p300 knockout compared with non-knockout mice in mRNA and protein level (TGF-β1: t = 1.945, P = 0.034;t = 1.902, P = 0.039;AP-1: t = 1.914, P = 0.038;t = 1.802, P = 0.041). Conclusions: p300 plays a crucial role in the pathogenesis of HSPN. p300 can down-regulate the expression of resistance genes (AP-1 and TGF-β1) by binding with GRα to prevent further renal injury and glucocorticoid resistance. Therefore, p300 is a promising new target in glucocorticoid therapy in HSPN.

Effects of Chinese herbs in children with Henoch-Schonlein purpura nephritis:a randomized controlled trial

OBJECTIVE:To research the curative effect of Chinese herbs for clearing away heat,promoting diuresis,nourishing the kidney,and consolidating essence in children with Henoch-Schonlein purpura nephritis(HSPN)with internal accumulation of damp-toxin using randomized controlled observations on large samples.To seek the mechanism of the therapy and its scope of indications.METHODS:Overall,186 children with HSPN were randomly divided into two groups:treatment group(n=126)treated with Chinese herbs for clearing heat and promoting diuresis and a control group(n=60)treated with Western Medicine.The treatment was carried out for three courses of 4weeks each.We recorded changes in patient urine routines,24 h urinary protein,blood-coagulating series,immunoglobulin and T-cell subgroups,and improvements in main symptoms.We evaluated the alleviation of clinical symptoms and the improvement of proteinuria,hematuria,and other lab-oratory test results.Finally,we analyzed the patient population suitable for this therapy according to the relationship between the grouping of patient body weight and curative effect.RESULTS:Damp-heat syndrome improved in the treatment group,with a significant difference in total effective rate after a 4-week treatment(χ2=13.5220,P=0.0002)and in curative rate after a12-week treatment(χ2=6.3410,P=0.0118),compared to those in the control group.The curative effect in the treatment group was greater than that in the control group but there was no statistical difference between the two groups.The curative effect after a 4-week treatment of patients in the treatment group weighing 30 kg or less based on Traditional Chinese Medicine(TCM)signs and urinary protein was significantly greater than that in the control group.However,there was no statistical difference in the curative effect on urinary red cells and various indexes after a 12-week treatment between the two groups.CONCLUSION:Therapy for clearing away heat,promoting diuresis,nourishing the kidney,and consolidating essence using TCM is effective in children with HSPN from internal accumulation of damp-toxin.The therapy is especially suitable for patients weighing 30 kg or less.The curative effect may be related to the improvement of immune function and blood-coagulation.

紫癜性肾炎患儿纤维蛋白原与国际小儿肾脏病研究组病理分级及肾单位微观病变的关系研究

背景 临床中紫癜性肾炎(HSPN)患儿多存在纤维蛋白原(FIB)升高现象,但FIB与肾脏病变相关性的研究较少。目的 探讨HSPN患儿FIB与国际小儿肾脏病研究组(ISKDC)病理分级及肾单位部分微观病理变化的相关性,明确FIB能否评估HSPN患儿肾损伤轻重。方法 收集2017年12月—2022年12月在河南中医药大学第一附属医院儿科医院肾病病区住院同时行肾活检的HSPN患儿922例,汇总其做肾活检期间的临床信息、FIB及肾脏病理信息,并依据FIB水平将患儿分为A组(偏低)<2.38 g/L、B组(标准)2.38~4.98 g/L、C组(偏高)>4.98 g/L。采用Spearman秩相关分析探究FIB与ISKDC病理分级、肾小球系膜增生比例、新月体增生比例及肾小球急慢性病变情况的相关性;再通过受试者工作特征(ROC)曲线分析FIB对肾单位微观病理变化的预测情况。结果 922例已做肾活检的HSPN患儿中,FIB为(3.48±1.01)g/L。A组113例,FIB偏低率占12.26%;B组734例,FIB标准率占79.61%;C组75例,FIB偏高率占8.13%。ISKDC病理分级中Ⅱa型173例(18.76%)、Ⅱb型29例(3.15%)、Ⅲa型466例(50.54%)、Ⅲb型232例(25.16%)、Ⅳ型及以上22例(2.39%)(其中Ⅳa型2例,Ⅳb型18例,Ⅴ型2例)。Spearman秩相关分析结果显示,HSPN患儿FIB及FIB分组与肾脏病理ISKDC分级(r_(s)=0.146,P<0.001;r_(s)=0.129,P<0.001)呈正相关性。922例HSPN患儿中有911例(98.80%)存在系膜细胞增生,655例(71.04%)存在新月体增生。Spearman秩相关分析结果显示,FIB、FIB分组均与系膜细胞增生率呈弱正相关性(r_(s)=0.092,P=0.005;r_(s)=0.096,P=0.003),与新月体增生率呈正相关性(r_(s)=0.132,P<0.001;r_(s)=0.830,P=0.012)。922例HSPN患儿中肾小球急性病变763例(82.75%)、急慢性病变97例(10.52%)、慢性病变62例(6.73%)。HSPN患儿FIB与肾小球病变的急慢性情况呈正相关(r_(s)=0.145,P<0.001)。同时,HSPN患儿部分肾活检指标FIB比较,差异有统计学意义(P<0.05)。ROC曲线显示,FIB对肾小球硬化的灵敏度最高(灵敏度=0.900,特异度=0.303),FIB最佳截断值为2.835 mg/L;FIB对小管间质纤维化正向预测的ROC曲线下面积(AUC)=0.623,对小管细胞颗粒变性反向预测的AUC=0.641。结论 FIB可作为一项反映HSPN患儿肾脏病理变化轻重的实验室检查指标,能反映肾脏病理分级的轻重,与肾小球硬化、球囊粘连等肾单位微观指标关系密切,可协助临床诊断和治疗。

Identification of 8 Rare Deleterious Variants in ADAMTS13 by Next-generation Sequencing in a Chinese Population with Thrombotic Thrombocytopenic Purpura

Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.