OBJECTIVE: To investigate the risk factors of different types of Henoch-Schönlein purpura (HSP) in Tibetan patients at high altitude, as to provide reference for correctly identifying high-risk patients. METHODS: A retrospective study was used to analyze the 304 HSP patients admitted to Tibet Autonomous Region People's Hospital from April 2014 to March 2022. The gender, age, allergic history, family history, clinical type, laboratory indexes (hemoglobin, platelet count, eosinophil, C-reactive protein (CRP), albumin, immunoglobulin G, immunoglobulin A, complement C3 and C4) were analyzed retrospectively. Univariate and multivariate Logistic regression analysis to screen for risk factors affecting different types of HSP. RESULTS: Renal HSP patients showed higher IgA [(9.2±1.7) g/L vs. (6.4±2.4) g/L, P=0.015], lower complement C3 [(203.3±21.6) mg/dL vs. (301.1±19.5) mg/dL, P=0.043], and complement C4 [(33.5±2.3) mg/dL vs. (53.0±7.2) mg/dL, P=0.032]. The patients with abdominal HSP showed lower levels of hemoglobin [(119.6±19.6) g/L vs. (146.6±47.3) g/L, P=0.038] and plasma albumin [24.8 (22.1, 33.9) g/L vs. 32.6 (24.6, 35.1) g/L, P=0.045]. The patients with articular HSP exhibited higher CRP [13.5 (0.2, 20.6) g/L vs. 7.5 (0.1, 15.2) g/L, P=0.036] and erythrocyte sedimentation rate (ESR) [24 (5, 40) mm/h vs. 15 (4, 30) mm/h, P=0.049]. Elevated IgA and decreased complement C4 were risk factors for renal HSP, anemia and decreased plasma albumin were risk factors for abdominal HSP, and elevated CRP was a risk factor for articular HSP. CONCLUSION The clinical characteristics of different types of HSP in plateau areas were different. Patients with high IgA, low complement C4, anemia, hypoalbuminemia, and significantly elevated CRP should be highly vigilant. Early and effective intervention can improve the clinical efficacy, avoid severe development, and improve the prognosis.
Humans ; Retrospective Studies ; Tibet/epidemiology* ; Complement C3/analysis* ; IgA Vasculitis/complications* ; Altitude ; Complement C4 ; C-Reactive Protein/analysis* ; Immunoglobulin A ; Risk Factors ; Anemia ; Hemoglobins/analysis* ; Serum Albumin/analysis*

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans ; Fecal Microbiota Transplantation ; Complement C3 ; Convalescence ; Prospective Studies ; Feces

OBJECTIVE: To investigate the clinical features and laboratory characteristics of primary autoimmune hemolytic anemia (AIHA) patients with negative results of direct antiglobulin test (DAT) by tube test but positive results by microcolumn gel assay, in order to provide references for the diagnosis of these patients. METHODS: 59 patients diagnosed with primary AIHA in our hospital from January 2015 to December 2020 were retrospectively analyzed. According to the results of tube test and microcolumn gel assay, the cases were divided into 3 groups, and the clinical and laboratory characteristics of each group were compared. RESULTS: The cases were grouped as follows: Group I, cases with negative results by both methods of DAT (n=5); Group II, cases with negative results by tube test but positive results by microcolumn gel assay (n=26); Group III, cases with positive results by both methods of DAT (n=28). There was no significant difference in age and sex between Group II and other groups, whereas the positive rate of anti-IgG + anti-C3d of Group II was lower than that in Group III (P=0.015). The main clinical manifestations of Group II were chest tightness, shortness of breath, fatigue, as well as yellow skin and sclera or dark urine, but the incidence rate of these symptoms was not significantly different from other groups. Anemia related indexes in Group II such as red blood cell (RBC) count and hemoglobin (Hb) were lower than the reference intervals, but there was no significant difference compared with other groups. Hemolysis related indexes in Group II such as reticulocyte (Ret) ratio, indirect bilirubin (IBIL), lactate dehydrogenase (LDH) and free-hemoglobin (F-Hb) were higher than the reference intervals, and the latter two items were signficantly higher than those in Group I (P=0.031 and P=0.036). Serum complement C3 and C4 in Group II were higher than those in Group III (P=0.010 and P=0.037). CONCLUSION Anemia severity of primary AIHA patients who were negative of DAT by tube test but positive by microcolumn gel assay was similar to those with negative or positive results by both DAT methods, but the mechanism and degree of complement system involved in hemolysis might be different. Results above may be helpful for laboratory diagnosis of this kind of patients.
Anemia, Hemolytic, Autoimmune/diagnosis* ; Bilirubin ; Complement C3 ; Coombs Test/methods* ; Erythrocytes ; Hemolysis ; Humans ; Lactate Dehydrogenases ; Negative Results ; Retrospective Studies

Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.
Male ; Child ; Humans ; Homozygote ; Complement C3 ; Antibodies, Antinuclear ; DNA Copy Number Variations ; Sequence Deletion ; Interferons ; Lupus Erythematosus, Systemic/genetics* ; Antiviral Agents ; Endodeoxyribonucleases

OBJECTIVE: To investigate the effect of complement C3 on the prognosis of patients with multiple myeloma (MM), and to establish a predictive model to evaluate the overall survival. METHODS: Eighty newly diagnosed MM patients were enrolled, and clinical characteristics, such as sex, age, platelet count, white blood cell count, ISS stage, FISH, levels of kappa and lammda chain, complement C3 and C4 were retrospectively analyzed. Cox regression model was used for univariate and multivariate analysis about risk factors that affecting the prognosis of the MM patients. A nomogram based on C3 level was established for predicting the prognosis of MM patients. RESULTS: The average age of the MM patients was 63.15±10.41, including 36 males and 44 females. The median overall survival (OS) was 36.3 months, and the median progression-free survival (PFS) was 35.2 months, the 3-year OS rate and PFS rate of the MM patients were 67.5% and 52.5%, respectively. The variants selected by univariate analysis were put into multivariate regression model, the result showed that C3 level ≥0.7 U/L and PLT count <100×10 CONCLUSION Patients with C3 level≥0.7 U/L or PLT count <100×10
Complement C3 ; Female ; Humans ; Male ; Multiple Myeloma ; Platelet Count ; Prognosis ; Retrospective Studies

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
Animals ; Astrocytes/metabolism* ; Complement C3/metabolism* ; Epilepsy ; Mice ; Neurons/pathology* ; Status Epilepticus ; TRPV Cation Channels/metabolism*

OBJECTIVE: To investigate the significance of detecting serum complement C3 and C4 in patients with multiple myeloma (MM) and to explore its correlation with myeloma bone disease (MBD). METHODS: The levels of serum complement C3 and C4 in 69 MM patients and 30 healthy people were examined by scatter nephelometry. The bone density of L1-4 vertebral body, bilateral femoral neck and bilateral hip joints were measured by dual energy bone density meter (DXA). RESULTS: The levels of serum complement C3 and C4 in MM patients significantly increased in comparison with that in healthy people (P＜0.01). The patients in advanced clinical stage exhibited a higher levels of C3 and C4 than those in stable stage (P＜0.01). In addition, the patients with grade C of MBD had a higher levels of serum complement C3 and C4 than those in patients with grade A and B of MBD (P＜0.01). The levels of serum complement C3 and C4 in MM patients negatively correlated with bone density in L1-4 vertebral body, bilateral femoral necks and hip joints. The correlation coefficients were r=-0.938, r=-0.659, r=-0.745, r=-0.748, r=-0.596 in complement C3 and r=-0.908, r=-0.623, r=-0.710, r=-0.714, r=-0.595 in complement C4, respectively. CONCLUSION The levels of complement C3 and C4 positively correlate with the severity of bone disease and bone density in MM patients, which suggests that complement C3 and C4 plays important roles in the development of MBD. The levels of serum C3 and C4 may be the sensitive biomarkers of MBD.
Biomarkers ; Complement C3 ; metabolism ; Complement C4 ; metabolism ; Femur Neck ; Humans ; Multiple Myeloma

OBJECTIVE: To study the clinical value of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in the evaluation of immune status in children with hand-foot-mouth disease (HFMD). METHODS: A total of 282 children with HFMD were enrolled as the HFMD group, and 130 healthy children were enrolled as the healthy control group. The percentages of peripheral CD3, CD4, and CD8 T lymphocytes, CD19 B lymphocytes, and CD56 natural killer cells were measured. The CD4/CD8 ratio was calculated. The levels of immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), and complement C3 and C4 were measured. RESULTS: The multivariate analysis showed that compared with the healthy control group, the HFMD group had significantly lower percentages of CD3, CD4, and CD8 T lymphocytes and levels of complement C3 and C4 (P<0.05), as well as significantly higher percentage of CD56 natural killer cells and level of IgG (P<0.05). The individual effect analysis showed that the children aged 0-3 years in the HFMD group had a significantly higher CD4/CD8 ratio than the healthy control group (P<0.05); boys aged 0-3 and ≥3 years in the HFMD group had a significantly higher level of IgM than the healthy control group (P<0.05); boys aged ≥3 years and girls aged 0-3 years in the HFMD group had a significantly lower level of IgA than the healthy control group (P<0.05). CONCLUSIONS Cellular and humoral immunity disorders are observed in children with HFMD. The monitoring of lymphocyte subsets and immunoglobulin levels can provide a laboratory basis for immune status assessment in children with HFMD.
Child, Preschool ; Complement C3 ; Complement C4 ; Female ; Hand, Foot and Mouth Disease ; Humans ; Immunoglobulins ; Infant ; Infant, Newborn ; Killer Cells, Natural ; Lymphocyte Count ; Lymphocyte Subsets ; Male

Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy, is distinguished from the typical form by the absence of a preceding verotoxin-producing Escherichia coli infection. Notably, aHUS occurs in association with genetic or acquired disorders causing dysregulation of the alternative complement pathway. Patients with aHUS may show the presence of anti-complement factor H (CFH) autoantibodies. This acquired form of aHUS (anti-CFH-aHUS) primarily affects children aged 9–13 years. We report a case of a 13-year-old Lao girl with clinical features of aHUS (most likely anti-CFH-aHUS). The initial presentation of the patient met the classical clinical triad of thrombotic microangiopathy (microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury) without preceding diarrheal illness. Low serum levels of complement 3 and normal levels of complement 4 indicated abnormal activation of the alternative complement pathway. Plasma infusion and high-dose corticosteroid therapy resulted in improvement of the renal function and hematological profile, although the patient subsequently died of infectious complications. This is the first case report that describes aHUS (possibly anti-CFH-aHUS) in Laos.
Adolescent ; Anemia, Hemolytic ; Atypical Hemolytic Uremic Syndrome ; Autoantibodies ; Child ; Complement C3 ; Complement C4 ; Complement Factor H ; Complement Pathway, Alternative ; Female ; Humans ; Immunosuppression ; Kidney ; Laos ; Plasma ; Shiga-Toxigenic Escherichia coli ; Thrombocytopenia ; Thrombotic Microangiopathies

Pemphigus represents a group of autoimmune blistering diseases caused by autoantibodies against desmogleins (Dsgs), a class of desmosomal cadherins. Recently, several pemphigus patients only with desmocollin (Dsc) 3-specific antibodies have been reported. Here, we report a case of pemphigus herpetiformis (PH), where only anti-Dsc3-specific antibodies but not anti-Dsg antibodies were detected. A 76-year-old woman presented with a 3-year history of blister formation. Physical examination revealed pruritic erythemas with vesicles on the trunk and legs, but no lesions of the oral mucosa. A skin biopsy specimen revealed intraepidermal blister containing neutrophils, eosinophils, and lymphocytes. Direct immunofluorescence (IF) showed immunoglobulin G (IgG) and complement 3 (C3) depositions on the keratinocyte cell surfaces. Indirect IF showed IgG anti-keratinocyte cell surface antibodies. These findings hinted at a diagnosis of pemphigus. However, repeated enzyme-linked immunosorbent assays (ELISAs) for both anti-Dsg1 and 3 antibodies proved to be negative. Immunoblotting of normal human epidermal extracts revealed Dsc antibodies, and recently established ELISAs using human Dsc1-Dsc3 recombinantly expressed in mammalian cells detected anti-Dsc3 antibodies. Based on these clinical, histopathological, and immunological findings, the patient was diagnosed as PH with only anti-Dsc3 antibodies. Treatment with corticosteroid prednisolone and steroid-sparing agent dapsone accomplished complete clinical remission of the patient.
Aged ; Antibodies* ; Autoantibodies ; Biopsy ; Blister ; Complement C3 ; Dapsone ; Desmogleins ; Desmosomal Cadherins ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Erythema ; Female ; Fluorescent Antibody Technique, Direct ; Humans ; Hydrogen-Ion Concentration ; Immunoblotting ; Immunoglobulin G* ; Immunoglobulins* ; Keratinocytes ; Leg ; Lymphocytes ; Mouth Mucosa ; Neutrophils ; Pemphigus* ; Physical Examination ; Prednisolone ; Skin