Subacute combined degeneration of spinal cord with autoimmune disease in children: a case report / 中华神经科杂志

The clinical manifestations of subacute combined degeneration of spinal cord (SCD) in children are complex and vary greatly. Due to the fact that some patients with SCD may be complicated with autoimmune diseases, the high early misdiagnosis and missed diagnosis rates are observed. One case of 13-year old female with severe anemia, multiple joint swelling and pain in left limbs and paralysis of bilateral lower limbs with the extremely low level of serum vitamin B12 and poly-glandular involvement as well as a variety of positive auto-antibodies (anti-intrinsic factor antibody, anti-parietal cell antibody, thyroid peroxidase antibody, thyroid globulin antibody and perinuclear anti-neutrophil cytoplasmic antibody) was retrospectively analyzed. The patient was diagnosed as SCD with autoimmune disease (undifferentiated connective tissue disease and autoimmune polyglandular syndrome). The patient′s condition gradually alleviated after high-dose intravenous methylprednisolone, immunoglobulin, naproxen (then changed to hydroxychloroquine 1 month later), vitamin B12 and levothyroxine sodium tablets supplementation, blood transfusion and rehabilitation. SCD with autoimmune diseases is rare in children, and the clinical manifestations vary greatly. Early recognition and early treatment can improve the prognosis of SCD. The clinical data of this child were retrospectively analyzed, so as to improve the understanding of the disease by clinicians.

COVID-19, glomerulonefritis ANCA y anti-membrana basal glomerular. Caso clínico / Association of COVID-19 and glomerulonephritis with ANCA and anti-glomerular basement membrane antibodies. Report of one case

Renal involvement in COVID-19 infection is varied and worsens its outcome and prognosis. However, the association of COVID-19 infection with glomerulonephritis is exceptional. We report a 46-year-old woman with COVID-19 who had an acute kidney injury and ANCA associated glomerulonephritis two weeks after the onset of the disease. The kidney biopsy showed a crescentic glomerulo-nephritis and the presence of anti-glomerular basement membrane antibodies (GBM-Abs). She was treated with steroids and oral cyclophosphamide with good response without requiring plasmapheresis. Plasma anti GBM-Abs were negative. This case suggests that the presence of anti-GBM-Abs in the kidney, was temporally related to COVID-19 pulmonary damage. The absence of plasma antibodies is probably due to transient production and glomerular adsorption, but with unknown pathogenic role.

IgA nephropathy in patients with serum anti-neutrophil cytoplasmic autoantibody (ANCA) positivity: case series / Nefropatia por IgA em pacientes com anticorpo anticitoplasma de neutrófilo positivo: série de casos

Abstract Some cases of patients with IgA nephropathy diagnosed via kidney biopsy and antineutrophil cytoplasmic antibody (ANCA) positivity have been reported. This article describes a case series comprising patients with IgA nephropathy and ANCA positivity seen at a medical center in the city of São Paulo, Brazil, from 1996 to 2016. A total of 111 patients underwent diagnostic kidney biopsies for IgA nephropathy. Five were ANCA-positive at the time of diagnosis; their mean age was 45 ± 15.3 years and they were predominantly females with a mean proteinuria of 2.2 ± 0.9 g/day and a median serum creatinine level of 2.5 (2.0 - 8,6) mg/dL; all had hematuria. Four of the five were cANCA-positive (80%); all had normal serum C3 and C4 levels; and 80% were positive for ANA. One case presented an association with infection, but no associations were found with medication. One patient had granuloma and another had a collapsing lesion. This article describes the cases of five ANCA-positive patients (with predominantly cANCA positivity) submitted to diagnostic kidney biopsies for IgA nephropathy; one patient had a collapsing lesion, but progressed well.

Resumo Alguns casos clínicos de biópsia renal diagnóstica de nefropatia por IgA em pacientes com títulos séricos positivos de anticorpo anticitoplasma de neutrófilos (ANCA) vêm sendo publicados. Descreve-se uma série de casos de nefropatia por IgA com ANCA positivo de centro único da cidade de São Paulo, Brasil, no período de 1996 a 2016. No período estudado, houve 111 pacientes com biópsia renal com diagnóstico de nefropatia por IgA; destes, 5 tinham ANCA positivo ao diagnóstico com média de idade de 45 ± 15,3 anos, predominando o sexo feminino, com média de proteinúria de 2,2 ± 0,9 g/dia, hematúria presente em 100% dos casos e mediana de creatinina sérica de 2,5 (2,0 - 8,6) mg/dL. O cANCA foi o padrão mais encontrado, em 4 dos 5 casos (80%), com os níveis séricos das frações de complemento C3 e C4 normais em todos e FAN positivo em 80% dos casos. Houve associação com infecções em um caso, mas sem associação com medicações. À microscopia óptica, um dos pacientes tinha granuloma e outro, lesão colapsante. Em resumo, descreve-se cinco casos de pacientes com biopsia renal diagnóstica de nefropatia por IgA com ANCA sérico positivo predominando cANCA, destacando um paciente desse grupo com microscopia óptica com lesão colapsante que, apesar disso, teve boa evolução.

Prevalência de positividade do anticorpo ANCA em pacientes hemodialisados / Prevalence of Positive ANCA Antibody in Patients in Hemodialysis

Objetivo: Estimar a prevalência do anticorpo anticitoplasma de neutrófilos (ANCA) positivo em pacientes submetidos à hemodiálise, assim como também associar essa prevalência às características sociodemográficas e clínicas destes pacientes. Métodos: Estudo transversal realizado em 78 pacientes de uma Clínica de Hemodiálise no Sul de Santa Catarina nos meses de agosto a novembro de 2013. Foi realizada entrevista, coleta de dados em prontuário eletrônico e pesquisa do anticorpo anticitoplasma de neutrófilos por imunofluorescência indireta WAMA em plasma heparinizado. Resultados: A prevalência de anticorpo anticitoplasma de neutrófilos reagente em amostra titulada 1:10 foi de 24,4%, sendo que 10,3% apresentaram padrão c-ANCA e 14,1% apresentaram padrão p-ANCA, do total. Não foram observadas associações com características clínicas e sociodemográficas. Conclusão: Com base na alta prevalência de anticorpo anticitoplasma de neutrófilos positivo encontrada neste estudo, salienta-se a necessidade de mais estudos nesse grupo de pacientes para definição da contribuição deste exame no diagnóstico e prognóstico da doença renal e suas complicações

Objective: To estimate the Antibodies, Antineutrophil Cytoplasmic (ANCA) prevalence in patients submitted to hemodialysis, as well as associate this prevalence to sociodemographic and clinical characteristics of these patients. Methods: Cross-sectional study performed with 78 users from a Hemodialysis Clinic in Southern Santa Catarina on the period from August to November 2013. Interviews, data collection of electronic records and antibodies, antineutrophil cytoplasmic research by WAMA indirect immunofluorescence on heparinized plasma were performed. Results: The prevalence of ANCA reagent 1:10 titrated sample was 24.4%, and 10.3% had c-ANCA pattern and 14.1% had p-ANCA pattern, from total sample. No associations were observed with clinical and sociodemographic characteristics. Conclusions: Based on the high antibodies, antineutrophil cytoplasmic prevalence in this study, and no statistically significant association with clinical and sociodemographic characteristics, we emphasize the need for more studies on this group of patients to determine the contribution of this exam in the diagnosis and prognosis of kidney disease and its complications.

Clinical analysis of 18 cases of infectious endocarditis with positive anti-neutrophil cytoplasmic anti-bodies / 中华风湿病学杂志

Objective:To study the clinical features of infective endocarditis (IE) with positive anti-neutrophil cytoplasmic antibodies (ANCA) in order to improve the level of diagnosis and treatment.Methods:Eighteen IE cases with positive ANCA admitted to the First Affiliated Hospital of Zhengzhou University from June 2016 to July 2021 were collected. The demographic information, clinical symptom, laboratory tests, imaging examinations, treatment and clinical outcomes were analyzed retrospectively. Statistical program for social sciences (SPSS) 20.0 statistical software was used for analysis. Enumeration data were expressed as the number of cases and percentage (%), and measurement data were expressed as Mean± SD. Results:Twelve cases were male and 6 cases were female, with an average age of (50±16) years. Sixteen patients had positive PR3-ANCA, in which 2 cases had positive myeloperoxidase (MPO)-ANCA. The major clinical manifestations included fever (88.9%, 16/18), anemia (72.2%, 13/18), splenomegaly (44.4%, 8/18), cardiac murmur (33.3%, 6/18), arthralgia (22.2%, 4/18), liver damage (22.2%, 4/18), thromboembolic events (16.7%, 3/18), Osler's node (11.1%, 2/18) and renal dysfunction (11.1%, 2/18). Higher C-reactive protein (CRP), erythrocyte sedimentation (ESR) and procalcitionin (PCT) were detected in 83.3% (15/18) patients. The positive rate of blood culture was 50.0%(9/18) and streptococcus was the most common pathogen (77.8%, 7/9). Echocardiograms of all patients showed abnormal vegetation, most commonly involving the mitral valve (66.7%, 12/18) and aortic valve (33.3%, 6/18). Two patients were misdiagnosed as ANCA associated vasculitis (AAV), but the other one was diagnosed as AAV with IE as the first manifestation. Except for one case who died of multiple organ failure, all cases reached clinical recovery after surgery and antibiotic therapy.Conclusion:IE patients with positive ANCA may present with the clinical manifestations similar to AAV. We should highly alert to avoid misdiagnosis and treatment.

Clinicopathologic characteristics of lupus nephritis with positive antineutrophil cytoplasmic antibody / 中华肾脏病杂志

Objective:To explore the clinical and histopathologic features of lupus nephritis (LN) patients with positive antineutrophil cytoplasmic antibody (ANCA), so as to provide more theoretical basis to recognize and treat this disease.Methods:Clinical data of biopsy-proven LN patients with ANCA test in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2002 to September 11, 2020 were collected and analyzed retrospectively. The difference of clinical data, laboratory examination, and pathological examination of renal biopsy between ANCA-positive group and ANCA-negative group. The clinicopathological characteristics between different ANCA serotypes were compared.Results:A total of 1 304 patients with LN confirmed by renal biopsy and ANCA test results were enrolled. Eighty ANCA-positive patients from 1 304 LN patients were screened. There are 55(68.8%) ANCA-positive LN patients with positive anti-myeloperoxidase antibodies (MPO). There were 14(17.5%) ANCA-positive LN patients with positive anti-proteinase 3 antibodies (PR3), and 11(13.8%) ANCA-positive patients with double positive antibodies of MPO and PR3. ANCA-positive LN patients had significantly higher serum creatinine [135.5(68.0, 361.8) μmol/L vs 88.0(64.0, 165.0) μmol/L, P=0.004] and blood urea nitrogen [12.35(6.35, 21.18) mmol/L vs 8.60 (5.50, 15.70) mmol/L, P=0.026] as well as lower estimated glomerular filtration rate [45.70(13.83, 84.10) ml·min -1·(1.73 m 2) -1 vs 66.75(38.43, 96.22) ml·min -1·(1.73 m 2) -1, P=0.001] than ANCA-negative patients (stratified sampling of 160 patients). ANCA-positive LN patients had higher chronicity index than ANCA-negative LN patients [3(2, 7) vs 2(0, 5), P=0.006]. There were statistically significant difference in hemoglobin, serum creatinine and estimated glomerular filtration rate among ANCA-positive group, ANCA-negative group, and MPO-ANCA and PR3-ANCA double positive group. MPO-ANCA and PR3-ANCA double positive LN patients had the lowest hemoglobin and estimated glomerular filtration rate, and highest serum creatinine among the three groups (all P<0.05). Conclusions:ANCA-positive LN patients have worse renal function and higher renal histological chronicity index than ANCA-negative LN patients, especially for patients with double positive MPO-ANCA and PR3-ANCA. More stringent monitoring and therapy may be needed in this subgroup of LN patients.

Clinical characteristics and risk factors of antineutrophil cytoplasmic antibody-associated vasculitis complicated with infection / 中华肾脏病杂志

Objective:To investigate the characteristics and risk factors of infection in newly diagnosed patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods:The clinical data of AAV patients (followed up for at least 6 months) in Affiliated Hospital of Qingdao University from September 2012 to September 2020 were retrospectively collected. According to whether infection occurred during follow-up, the patients were divided into infection group and non-infection group. The clinical characteristics and infection status of the two groups were analyzed, and the Cox regression analysis model was used to explore the influencing factors of infection.Results:A total of 236 AAV patients were enrolled in this study, including 128 females (54.2%) and 108 males (45.8%), with a median age of 66.00 (59.76, 71.99) years. There were 202 patients (85.6%) with positive myeloperoxidase (MPO)-ANCA and 34 patients (14.4%) with positive protease 3 (PR3) -ANCA. There were 77 cases in the infection group and 159 cases in the non-infection group. A total of 121 infections occurred in 77 patients, and 54 infections (44.6%) occurred within 6 months after initial diagnosis. In the infection group the proportion of patients with hypertension history, pulmonary underlying diseases and patients who received hormone pulse therapy or plasma exchange, the incidence of lung, kidney, heart and gastrointestinal involvement, the level of serum creatinine and five factors score (FFS) at initial diagnosis were significantly higher than those in the non-infection group (all P<0.05), while the estimated glomerular filtration rate (eGFR) was significantly lower ( P<0.05). Lung (73.6%) was the main infection organ of AAV patients. The most common pathogenic microorganisms were bacteria (64.0%), mainly Pseudomonas aeruginosa and Staphylococcus aureus, followed by fungi (33.7%, mainly Candida albicans). Multivariate Cox regression analysis showed that lung involvement ( HR=1.682, 95% CI 1.034-2.734, P=0.036) and gastrointestinal involvement ( HR=2.976, 95% CI 1.219-7.267, P=0.017) were the independent influencing factors for infection in AAV patients. Conclusions:AAV patients have a higher incidence of infection within 6 months after initial diagnosis. The most common organ of infection in AAV patients is the lung, and the common pathogens are Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Lung involvement and gastrointestinal involvement are the independent risk factors for infection in AAV patients.

Clinical analysis of antineutrophil cytoplasmic antibody-associated vasculitis in 13 children / 中华肾脏病杂志

Objective:To investigate the clinical manifestations, pathological characteristics, treatment and prognosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in 13 children.Methods:The clinical and pathological data of 13 cases of AAV in children′s Hospital of Nanjing Medical University from June 2000 to December 2021 were retrospectively analyzed.Results:Among the 13 cases, 12 cases were diagnosed with microscopic polyangiitis (MPA) and 1 case was granulomatosis with polyangiitis (GPA), including 10 females and 3 males. The onset age ranged from 3 years and 11 months to 13 years and 10 months. The most frequently involved organ was the kidney (12 cases, 92.3%), followed by respiratory system (7 cases, 53.8%), skin (5 cases, 38.5%), digestive system (4 cases, 30.8%), nervous system (4 cases, 30.8%) and cardiovascular system (3 cases, 23.1%). There were 10 cases with orthotic anemia, 7 cases with positive antinuclear antibody, and 3 cases with mildly decreased complement C3. Among the 12 children with renal impairment, 9 cases were accompanied by abnormal renal function at the beginning of the disease. Renal biopsy was classified according to the Berden as follows: sclerotic in 5 cases, crescentic 3 cases, focal in 2 cases and mixed in 2 cases. All children were treated with glucocorticoid combined with immunosuppressant. During the follow-up time from 8 months to 128 months, 4 cases acquired complete remission, 8 cases achieved partial remission and 1 case recurred after complete remission, and 7 cases progressed to chronic kidney disease stage 5. Three children with complete remission underwent repeated renal biopsy, including 2 cases of mixed type and 1 case of crescent type initially, and all changed to focal type.Conclusions:AAV in children occurs mainly in school-age female, and most of AAV in children is MPA. The clinical manifestations are various. Most of them have renal damage and anemia, and lung damage is also common. Patients with skin purpura onset may be misdiagnosed as Henoch-Schonlein purpura, and AAV with ANA positive or complement reduction should exclude systemic lupus erythematosus. Once the renal function is abnormal in AAV, especially estimated glomerular filtration rate<60 ml·min -1·(1.73 m 2) -1 and the pathological classification is sclerotic type or crescent type, it is difficult to reverse even after active treatment. Early diagnosis and treatment are very important for AAV.

Analysis of clinicopathological characteristics and renal prognosis of patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis / 中华肾脏病杂志

Objective:To determine the prognostic values of clinical and laboratory features at the time of presentation on renal survival of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis (MPO-ANCA-GN).Methods:A total of 172 patients with MPO-ANCA-GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2005 to December 2018 were enrolled. The baseline clinical characteristics and renal biopsy pathological data were analyzed, and the renal prognosis was followed up. The clinical and pathological characteristics of different renal prognosis in all patients and 112 patients who underwent renal biopsy were analyzed, and the related factors affecting renal survival were further discussed.Results:Among these 172 patients, 81 were males and 91 were females. The median serum creatinine at diagnosis was 343.7(174.2, 606.6) μmol/L and the median estimated glomerular filtration rate (eGFR) was 15.81(7.61, 38.04) ml·min -1·(1.73 m 2) -1. In total, 76 patients (44.2%) received initial renal replacement therapy (RRT). During a median follow-up duration of 20(3, 60) months, 73 patients (42.4%) progressed to end-stage renal disease (ESRD) and required dialysis, including 6 (8.2%) patients who entered RRT during follow-up and 67 (91.8%) patients who received RRT at the beginning. Among the 112 patients who underwent renal biopsy, the proportion of patients who progressed to ESRD in the sclerotic group was the highest (15/25, 60.0%). The baseline serum creatinine level ( P<0.001), urine red blood cell count ( P=0.012) and the proportion of glomerular sclerosis ( P=0.002) in the non-dialysis dependent group were significantly lower than those in the dialysis dependent group, while the levels of eGFR ( P<0.001), serum albumin ( P=0.002) and hemoglobin ( P<0.001) were higher than those of the dialysis-dependent group. Kaplan-Meier survival analysis showed that the renal survival rate of the focal group was the highest ( χ2=19.488, P<0.001, log-rank test), while the renal survival rate of the sclerotic group was significantly lower than that of the crescentic group ( χ2=5.655, P=0.017); higher levels of serum creatinine (>320 μmol/L, χ2=77.229, P<0.001) and urine red blood cell count (>300 cells/μl, χ2=8.511, P=0.004), lower levels of rheumatoid factor (<20 IU/ml, χ2=8.610, P=0.003), serum albumin (<30 g/L, χ2=11.060, P=0.001) and hemoglobin (<90 g/L, χ2=21.921, P<0.001) were associated with lower renal survival rate; in terms of treatment, the renal survival rate of the glucocorticoids plus mycophenolate mofetil group was significantly higher than that of the glucocorticoids plus cyclophosphamide ( χ2=5.056, P=0.025) or the glucocorticoids alone group ( χ2=16.459, P<0.001). Multivariate Cox regression showed that baseline serum creatinine >320 μmol/L ( HR=8.803, 95% CI 3.087-25.106, P<0.001) and serum albumin <30 g/L ( HR=2.566, 95% CI 1.246-5.281, P=0.011) were the related factors affecting renal survival. Conclusion:Serum creatinine and albumin levels of MPO-ANCA-GN patients at diagnosis may be the related factors that affect the patient's renal prognosis.

Clinical significance of the serum perinuclear antineutrophil cytoplasmic antibody and fecal calprotectin in prediction the severity of ulcerative colitis in children / 中国医师进修杂志

Objective To investigate the clinical value of perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and fecal calprotectin in predicting the severity of ulcerative colitis (UC) in children.Methods One hundred children with UC from March 2014 to March 2019 in Affiliated Dongfeng Hospital,Hubei University of Medicine were selected.According to the endoscopic severity index of ulcerative colitis (UCEIS),the children were divided into remission stage (29 cases);active stage (71cases),among whom 43 cases were mild-moderate,and 28 cases were severe.The serum levels of interleukin-6 (IL-6),procalcitonin (PCT),C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),albumin,platelet,hemoglobin,white blood cell and p-ANCA were detected,and the fecal calprotectin was detected.The clinical value of each index in predicting the severity of UC was determined by receiver operating characteristic (ROC) curve.Results The course of disease,IL-6,PCT,CRP,ESR,p-ANCA and calprotectin in remission stage children were significantly lower than those in active stage children:(3.14 ± 1.25) years vs.(3.73 ± 0.89) years,(10.08 ± 4.40)/μg/L vs.(15.84 ± 3.22) μg/L,(1.02 ± 0.38) μg/Lvs.(1.38 ± 0.43) μg/L,(15.92 ± 6.13) mg/L vs.(24.30 ± 6.06) mg/L,(14.75 ± 6.42) mm/1 h vs.(25.31 ± 6.98) mm/1 h,(17.19 ± 4.76) U vs.(28.01 ± 6.12) U and (504.82 ± 127.46) μg/g vs.(717.04 ± 142.30) μg/g,and there were statistical differences (P＜0.05 or ＜0.01).The IL-6,CRP,ESR,white blood cell,p-ANCA and calprotectin in mild-moderate children were significantly lower than those in sever children:(14.56 ± 2.72) μg/L vs.(17.82 ± 2.93) μg/L,(22.01 ± 5.32) mg/L vs.(27.83 ± 5.46) mg/L,(22.31 ± 4.46) mm/1 h vs.(29.91 ± 7.70) mm/1 h,(7.33 ± 1.33) × 109/L vs.(8.38 ± 1.90) × 109/L,(25.52 ± 5.22) U vs.(31.83 ± 5.44) U and (632.80 ± 82.51) μg/g vs.(846.42 ± 11.10) μg/g,and there were statistical differences (P＜0.01 or ＜:0.05).Pearson correlation analysis result showed that,in active children,the UCEIS had high positive correlation with fecal calprotectin (r =0.707,P＜0.01),mild positive correlation with p-ANCA,ESR,IL-6,CRP and albumin (r =0.660,0.650,0.626,0.592 and 0.486;P＜0.01),and low positive correlation with PCT and white blood cell (r =0.362 and 0.245,P＜0.01 or ＜0.05).ROC curve analysis result showed that the optimal cut-off value of p-ANCA was 23.40 U,and the area under curve (AUC) in diagnosis of active stage UC was maximum (0.923),with a specificity of 93.1％ and a sensitivity of 78.9％;the optimal cut-off value of fecal calprotectin was 732.69 μg/g,and the AUC in diagnosis of active stage UC was maximum (0.937),with a specificity of 93.0％ and a sensitivity of 92.9％.Conclusions Serum p-ANCA is useful for UC disease activity diagnosis in children,while fecal calprotectin is independent predictor of the severe of UC.

Comparison between enzyme-linked immunosorbent assay and indirect immunofluorescence for detection of antineutrophil cytoplasmic antibodies / Comparação entre os métodos de ensaio imunoenzimático e imunoflurescência indireta para a pesquisa de anticorpos anticitoplasma de neutrófilos

ABSTRACT Objective To evaluate the performance of enzyme-linked immunosorbent assay and indirect immunofluorescence methods for the detection of antineutrophil cytoplasmic antibodies in a routine clinical laboratory setting. Methods A total of 227 samples were tested by indirect immunofluorescence and enzyme-linked immunosorbent assay with antigen specificity for antiproteinase 3 and antimyeloperoxidase. The proportions of positive samples were compared by McNemar hypotheses and agreement was described by Cohen's Kappa coefficient. Results The agreement of the tests was 96.5%, and the Kappa coefficient obtained was 0.70 (95%CI: 0.50-0.90; p<0.001). Considering indirect immunofluorescence as the gold standard, the sensitivity of the enzyme-linked immunosorbent assay was 0.62 and the specificity was 0.99, with diagnostic accuracy in 96% of cases. Some samples were negative in enzyme-linked immunosorbent assay and positive in indirect immunofluorescence. This situation occurred in all immunofluorescence patterns, but particularly in atypical patterns. Two samples with antiproteinase 3 positivity were considered negative in indirect immunofluorescence. Conclusion The enzyme-linked immunosorbent assay had high specificity but lower sensitivity. The performance of indirect immunofluorescence increases diagnostic sensitivity, while the search for antiproteinase 3 by enzyme-linked immunosorbent assay may also add diagnostic power.

RESUMO Objetivo Avaliar o desempenho das metodologias de ensaio imunoenzimático e imunofluorescência indireta para a detecção de anticorpos anticitoplasma de neutrófilos em um contexto de laboratório clínico de rotina. Métodos Foram testadas 227 amostras pelas metodologias de imunofluorescência indireta e ensaio imunoenzimático com especificidades para anticorpos antiproteinase-3 e antimieloperoxidase. As proporções de amostras positivas foram comparadas por hipóteses de McNemar, e a concordância foi descrita pelo coeficiente Kappa de Cohen. Resultados A concordância dos testes foi 96,5%, e o coeficiente Kappa obtido foi 0,70 (IC95%: 0,50-0,90; p<0,001). Utilizando a imunofluorescência indireta como padrão-ouro, a sensibilidade do ensaio imunoenzimático foi de 0,62 e a especificidade, 0,99, com acurácia diagnóstica em 96% dos casos. Algumas amostras apresentaram resultados negativos por ensaio imunoenzimático e positivos por imunofluorescência. Isso ocorreu em amostras com vários padrões de fluorescência, mas particularmente nos casos com padrões atípicos. Duas amostras com positividade antiproteinase 3 foram consideradas negativas por imunofluorescência. Conclusão Os métodos de ensaio imunoenzimático tiveram alta especificidade, mas sensibilidade inferior. A realização da imunofluorescência indireta aumenta a sensibilidade diagnóstica, ao mesmo tempo que a pesquisa de antiproteinase 3 por ensaio imunoenzimático também pode agregar poder diagnóstico.

Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement / Glomerulonefrite rapidamente progressiva associada a ANCA em uma criança com acometimento renal isolado

ABSTRACT Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.

RESUMO A glomerulonefrite (GN) pauci-imune é mais comum em idosos em comparação com crianças, e a etiologia ainda não é completamente compreendida. A positividade do anticorpo citoplasmático antineutrófilo (ANCA) ocorre em 80% dos pacientes. Relatamos o caso de uma menina de 7 anos de idade que apresentou mal-estar e creatinina discretamente elevada, diagnosticada como glomerulonefrite rapidamente progressiva pauci-imune associada a ANCA com crescentes em 20 dos 25 glomérulos (80%). Destes 20 crescentes, 12 eram celulares, 4 fibrocelulares e 4 globalmente escleróticos. Ela não apresentava púrpura, artrite ou sintomas sistêmicos e respondeu bem ao tratamento imunossupressor inicial, apesar da histopatologia relativamente grave. A paciente recebeu três pulsos de metilprednisolona intravenosa (30 mg/kg em dias alternados) inicialmente e continuou com ciclofosfamida (2 mg/kg por dia) por via oral durante 3 meses com prednisona (1 mg/kg por dia). Em um mês, a remissão foi alcançada com creatinina sérica normal e a prednisona foi gradualmente reduzida. O caso desta criança com uma doença pediátrica relativamente rara enfatiza a importância do tratamento imunossupressor precoce e agressivo em pacientes com GN rapidamente progressiva renal associada à ANCA, mesmo com uma apresentação clínica leve. Como em nossa paciente, os achados clínicos e laboratoriais podem nem sempre refletir exatamente a gravidade da histopatologia renal e, assim, a biópsia renal é obrigatória nessas crianças para orientar a conduta clínica e auxiliar no prognóstico.

Risk factors for secondary infection in the treatment with anti-neutrophil cytoplasmic antibody-associated vasculitis / 中华肾脏病杂志

Objective To investigate the clinical characteristics and risk factors of secondary infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods One hundred and eighteen patients newly diagnosed with AAV at the institute of nephrology,Tongji hospital affiliated to Huazhong university of science and technology,from 2012 to 2017,were analyzed retrospectively.Induction therapy included single corticosteroids,combination of corticosteroids with cyclophosphamide and combination of corticosteroids with other immunosuppressive agents.End point was defined as moderate to severe infection which was diagnosed by the clinical and radiological manifestation as well as microbiological evidences.The infection-related survival curve was drawn to reflect the time when the infection occurred.The clinical baseline variables in patients with and without infection were compared.Multivariate Logistic regression model was used to determine the independent predictors of infection.Receiver-operating characteristic curve (ROC) was plotted for evaluating the predictive value of lymphocyte on moderate to severe infection.Results During followup of median 3 months (1-30 months),88 infection episodes were found in 63 (53.4％) patients,of which 54 times (61.4％) occurred within 6 months after treatment,46 times (52.3％) happened within 3 months after treatment.The most common organ of infection was lung (62.5％),and the most common pathogen was bacteria (51.1％).Multivariate Logistic regression model showed that lung involvement (OR=4.44,95％ CI 1.59-12.41),moderate reduction of lymphocyte in follow-up (OR=5.69,95％ CI 2.05-15.85) and severe lymphocyte reduction (OR=36.28,95％CI 3.45-381.17) were independent risk factors of secondary infection in AAV patients (all P ＜ 0.05).ROC curve showed that the area under the curve of lymphocyte as a predictor of severe infection was 0.767 (95％ CI 0.64-0.89,P ＜ 0.05).Based on lymphocyte less than 0.49× 109/L which was the cut-off value for predicting severe infection,the sensitivity and the specificity were 83.9％ and 71.9％,respectively.Conclusions Lung involvement and moderate-severe lymphopenia during follow-up are independent risk factors of secondary infection in AAV patients.Hence,physician should pay more attention to those patients,and adjust treatment in time to avoid the occurrence of infection.

Investigation on the production of anti-neutrophil cytoplasmic antibodies in chronic bronchitis rats / 中华肾脏病杂志

Objective To investigate the pathogenesis of the production of anti-neutrophil cytoplasmic antibodies (ANCA) in the rat models of chronic bronchitis (CB) with recurrent infections. Methods The CB models were made by double element of smoking and lipopolysaccharide (LPS) stimulation. The rats were divided into four groups, including normal control group (n=5), phorbol-12-myristate-13-acetate (PMA)-treated healthy rats control group (n=5), CB rats group (n=5) and PMA-treated CB rats group (n=6). Renal function of rats was detected. The histopathological lung and kidney tissues were observed by HE staining of paraffin section. Immunological markers, including myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA), proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) and citrullinated histone H3 (CitH3), were measured by enzyme-linked immune-sorbent assay (ELISA) at different time points. Correlation between CitH3 and MPO-ANCA was analyzed by the Spearman rank correlation. NETs components were further detected in lung and kidney tissue by confocal immunofluorescence and colocalization analysis. Results (1) The serum levels of CitH3 and MPO-ANCA in CB+PMA group showed an increased trend. Compared with those in the normal control group and CB rats group, the serum levels of CitH3 and MPO-ANCA in CB+PMA group increased significantly at the sixth week (both P＜0.05). Serum CitH3 levels in rats were positively correlated with serum MPO-ANCA levels (rs=0.490,P=0.024). (2) There were pathological manifestations of CB in the lung tissues of rats in CB group and CB+PMA group, and no obvious abnormalities in the lung tissues of rats in the normal control group and control group. In the rat kidney tissue of CB+PMA group, there were inflammatory cells infiltrated in the glomerular and around the renal tubules, but glomerular necrosis was not found. No obvious abnormalities were observed in the kidney tissues of rats in the normal control group, PMA-treated healthy rats control group and CB group. (3) In the lung and kidney tissues of CB+PMA group NETs could be detected by confocal immunofluorescence analysis. Conclusion CB rats with the recurrent infections can release large amounts of NETs, in which the exposure of MPO antigen will break the immune tolerance and result in the production of MPO-ANCA.

The 461th case: fever, hematuria, and right lumbar pain / 中华内科杂志

A 56-year-old female was admitted to the Department of Rheumatology,Peking Union Medical College Hospital with complaint of recurrent fever and acute lumbar pain.Fever was complicated with malaise,cough and occasional blood-streaked sputum.Lab tests showed elevated white blood cell count,increased serum creatinine,erythrocyte sedimentation rate and C-reactive protein.Other lab findings included severe anemia,hematuria,and proteinuria.Immunological examinations were positive for antinuclear antibodies,antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibody.Ultrasonography and CT scan detected a huge spontaneous perirenal hematoma at right side.Angiography revealed multiple microaneurysms on bilateral renal arteries and branches.A diagnosis of systemic vasculitis was suggested.Under the combination therapy of corticosteroids and cyclophosphamide,the patient presented sustained remission for one year.This case indicates that prompt and sufficient treatment of primary disease is essential to a promising outcome.

Attach importance to the rational clinical application of anti-neutrophil cytoplasmic antibodies / 中华检验医学杂志

Vasculitis has a broad spectrum of diseases .Of the antibodies to vsculitis , anti-neutrophil cytoplasmic antibody ( ANCA ) , which was recommended by several international consensus , has been proved to be of diagnostic values , and is closely related to primary small vasculitis .It is necessary for clinicians to understand the significance of the results of ANCA in vasculitis and other ANCA positive diseases.

Progress in laboratory detection of anti-neutrophil cytoplasmic antibodies / 中华检验医学杂志

Along with the rapid development of biomedical technology and the clinical application of anti-neutrophil cytoplasmic antibody ( ANCA ) , the detection of ANCA by indirect immunofluorescence ( IIF) and the detection of specific autoantibodies of ANCA by various immunological methods have also been developed , which promoted the standardization of ANCA′s laboratory testing procedures .These advances have brought new opportunities and challenges to ANCA′s laboratory testing technology and its clinical application.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus

Abstract: Background: The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. Objectives: This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. Methods: A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Results: Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). Study limitations: The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. Conclusions: The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Anti-neutrophil cytoplasmic antibodies-associated vasculitis with lung hemorrhage in the patient on maintenance haemodialysis: a case report / 北京大学学报(医学版)

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is usually a multisystem disorder,and pulmonary renal syndrome is a common presentation.Patients with AAV are less likely to experience relapse when they progress to end-stage renal disease (ESRD).We report a rare case of diffuse alveolar hemorrhage (DAH) in relapsing AAV after eight years of haemodialysis.A 58-year-old woman was admitted to our hospital with the chief complaints of dyspnea and hemoptysis accompanied by anemia,fever,fatigue,and weight loss.She had elevated anti-myeloperoxidase (MPO) titer.The computer tomoghraphy showed diffuse alveolar hemorrhage.After the recurrent episode of AAV was diagnosed,she underwent the following therapy:Plasmapheresis was initiated within 24 h after admission,3 000 mL of plasma was removed per session,and the anticoagulation of citrate was applied during plasmapheresis.Five plasmapheresis treatments were performed,and after three apheresis sessions,the pulmonary hemorrhage ceased.Other treatments included a methylprednisolone bolus,tapered to oral prednisone and cyclophosphamide.Regular hemodialysis was scheduled.These treatments resulted in resolution of the inflammatory symptoms,DAH improved.Her anti-MPO level decreased.The patient was discharged in good condition.AAV with DAH is usually acute at the onset and is generally a condition with high morbidity and substantial mortality.Therefore,prompt diagnosis and aggressive treatment are needed to improve survival.

Henoch-Schönlein purpura with c-ANCA antibody in an adult

Abstract: The Henoch-Schönlein purpura is the vasculitis associated with deposits of immunoglobulin A in small vessels. Its association with cytoplasmic antineutrophil cytoplasmic antibodies is possible, but rare. This vasculitis is uncommon in adults and the main clinic manifestations are purpuric lesions in lower limbs with gastrointestinal symptoms and renal involvement. The present work describes a rare case of Henoch-Schönlein purpura in an adult with cytoplasmic antineutrophil cytoplasmic antibodies.