Guía de práctica clínica: tamizaje, diagnóstico y manejo de episodios agudos y profilaxis del angioedema hereditario ­ Parte II: Manejo y tratamiento / Clinical practice guidelines: screening, diagnosis and management of acute events and prophylaxis of hereditary angioedema ­ Part II: Management and treatment

El angioedema hereditario (AEH) es una enfermedad genética rara, con una prevalencia aproximada entre 1 por cada 50.000 habitantes, caracterizada por episodios de edemas a nivel subcutáneo y de mucosas (abdominal, genitourinario, respiratoria), siendo potencialmente mortal cuando hay afectación de la laringe. En Perú se estiman 600 pacientes con AEH. El AEH se puede clasificar del siguiente modo: con deficiencia del inhibidor de C1 (tipos I y II), y sin deficiencia del inhibidor de C1 (denominado anteriormente tipo III). El diagnóstico de laboratorio incluye prueba de complemento C4, prueba cuantitativa y cualitativa para inhibidor de C1 esterasa, y estudios genéticos. Existen tratamientos específicos a nivel mundial para crisis agudas y profilaxis en AEH. Sin embargo, en Perú el único tratamiento registrado actualmente es el ecallantide, útil en crisis agudas; además, podemos utilizar tratamientos alternativos como el ácido tranexámico y el danazol. En esta segunda parte de la Guía de Práctica Clínica, presentamos las recomendaciones para el manejo y el tratamiento del AEH.

Hereditary angioedema (HAE) is a genetic rare disease with a prevalence of approximately 1 per 50,000 inhabitants, characterized by episodes of edema at the subcutaneous level and mucous membranes (abdominal, genitourinary, respiratory), being potentially fatal when there is involvement of the larynx. In Peru, there are an estimated 600 patients with HAE. HAE can be classified as follows: with C1 inhibitor deficiency (types I and II), and without C1 inhibitor deficiency (previously called type III). Laboratory diagnosis includes C4 complement test, quantitative and qualitative test for C1 inhibitor esterase, and genetic studies. There are specific treatments worldwide for acute crises and prophylaxis in HAE; in Peru the only currently registered treatment is ecallantide, useful in acute crises; we can also use alternative treatments such as tranexamic acid and danazol. In this second part of the Clinical Practice Guide, we present the recommendations for the management and treatment of HAE.

Expression and diagnostic value of plasma miR-145 and miR-183 in children with lupus nephritis / 中国当代儿科杂志

OBJECTIVE@#To study the expression and diagnostic value of plasma miR-145 and miR-183 in children with lupus nephritis (LN).@*METHODS@#A total of 92 children with LN who were admitted from January 2016 to May 2019 were enrolled as the LN group, among whom 17 had type II LN, 15 had type III LN, 36 had type IV LN, 18 had type V LN, and 6 had type VI LN. Forty healthy children who underwent physical examination were enrolled as the healthy control group. According to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the 92 children with LN were further divided into a stable LN group with 34 children (SLEDAI score <10) and an active LN group with 58 children (SLEDAI score ≥10). RT-PCR was used to measure the expression of miR-145 and miR-183 in plasma. The receiver operating characteristic (ROC) curve was used to analyze the value of plasma miR-145, miR-183, and anti-dsDNA antibody in the diagnosis of LN. Pearson correlation analysis was used to investigate the correlation of the expression levels of miR-145 and miR-183 in plasma with laboratory markers.@*RESULTS@#The LN, active LN, and stable LN groups had significantly higher levels of anti-dsDNA antibody, C-reactive protein, serum creatinine (Scr), and blood urea nitrogen (BUN) than the control group (P<0.05). The active LN group had significantly higher SLEDAI score, anti-dsDNA antibody, Scr, and BUN than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower levels of complement C3, complement C4, and serum albumin (Alb) than the control group (P<0.05). The active LN group had a significantly lower level of Alb than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01). The active LN group had significantly lower plasma levels of miR-145 and miR-183 than the stable LN group (P<0.01). The children with difference types of LN had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01), and the type V-VI group and the type IV group had significantly lower plasma levels of miR-145 and miR-183 than the type II-III group (P<0.01). The ROC curve analysis showed that the optimal cut-off values of plasma miR-145, miR-183, and anti-dsDNA antibody were 1.05, 0.62, and 186.30 IU/mL respectively, in the diagnosis of LN, and the combination of these three indices had the largest area under the ROC curve of 0.896 (95%CI: 0.835-0.955), with a sensitivity of 90.5% and a specificity of 84.2%. In the children with LN, the plasma levels of miR-145 and miR-183 were negatively correlated with SLEDAI score, anti-dsDNA antibody, Scr, and BUN (P<0.05) and were positively correlated with complement C3, complement C4, and Alb (P<0.05).@*CONCLUSIONS@#There are significant reductions in the expression levels of miR-145 and miR-183 in plasma in children with LN, which are correlated with the activity level and pathological typing of LN. Combined measurement of miR-145, miR-183, and anti-dsDNA antibody has a high value in the diagnosis of LN.

Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onsetlupus nephritis

Abstract Background: Urinary parameters, anti-dsDNA antibodies and complement tests were explored in patients with childhood-Systemic Lupus Erythematosus (cSLE) early-onset lupus nephritis (ELN) from a large multicenter cohort study. Methods: Clinical and laboratory features of cSLE cases with kidney involvement at presentation, were reviewed. Disease activity parameters including SLEDAI-2 K scores and major organ involvement at onset and follow up, with accrued damage scored by SLICC-DI, during last follow up, were compared with those without kidney involvement. Autoantibodies, renal function and complement tests were determined by standard methods. Subjects were grouped by presence or absence of ELN. Results: Out of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years; 427 (50.5%) had ELN. There was no significant difference in the ELN proportion, according to onset age, but ELN frequency was significantly higher in non-Caucasians (p = 0.03). Hematuria, pyuria, urine casts, 24-h proteinuria and arterial hypertension at baseline, all had significant association with ELN outcome (p < 0.001). With a similar follow up time, there were significantly higher SLICC-DI damage scores during last follow up visit (p = 0.004) and also higher death rates (p < 0.0001) in those with ELN. Low C3 (chi-square test, p = 0.01), but not C3 levels associated significantly with ELN. High anti-dsDNA antibody levels were associated with ELN (p < 0.0001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies were not associated. Low C4, C4 levels, low CH50 and CH50 values had no significant association. High erythrocyte sedimentation rate (ESR) was associated with the absence of ELN (p = 0.02). Conclusion: The frequency of ELN was 50%, resulting in higher morbidity and mortality compared to those without ELN. The urinary parameters, positive anti-dsDNA and low C3 are reliable for discriminating ELN.(AU)

Atypical Hemolytic Uremic Syndrome in a 13-year-old Lao Girl: A Case Report

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.

Significance of Detecting Serum Complement C3 and C4 in Patients with Multiple Myeloma / 中国实验血液学杂志

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.

Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus

Abstract Background Complement component 4 (C4) gene copy number (GCN) affects the susceptibility to systemic lupus erythematosus (SLE) in different populations, however the possible phenotype significance remains to be determined. This study aimed to associate C4A , C4B and total C4 GCN and SLE, focusing on the clinical phenotype and disease progression. Methods C4 , C4A and C4B GCN were determined by real-time PCR in 427 SLE patients and 301 healthy controls, which underwent a detailed clinical evaluation according to a pre-established protocol. Results The risk of developing SLE was 2.62 times higher in subjects with low total C4 GCN (< 4 copies, OR = 2.62, CI = 1.77 to 3.87, p < 0.001) and 3.59 times higher in subjects with low C4A GCN (< 2 copies; OR = 3.59, CI = 2.15 to 5.99, p < 0.001) compared to those subjects with normal or high GCN of total C4 (≥4) and C4A (≥2), respectively. An increased risk was also observed regarding low C4B GCN, albeit to a lesser degree (OR = 1.46, CI = 1.03 to 2.08, p = 0.03). Furthermore, subjects with low C4A GCN had higher permanent disease damage as assessed by the Systemic Lupus International Collaborating Clinics - Damage Index (SLICC-DI; median = 1.5, 95% CI = 1.2-1.9) than patients with normal or high copy number of C4A (median = 1.0, 95% CI = 0.8-1.1; p = 0.004). There was a negative association between low C4A GCN and serositis ( p = 0.02) as well as between low C4B GCN and arthritis ( p = 0.02). Conclusions This study confirms the association between low C4 GCN and SLE susceptibility, and originally demonstrates an association between low C4A GCN and disease severity.

Levels of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in children with hand-foot-mouth disease / 中国当代儿科杂志

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.

T cell subsets and immunoglobulin G levels are associated with the infection status of systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Estimación del intervalo de referencia para C3 y C4 en población adulta de un hospital del Gran Buenos Aires / Estimation of the reference range for C3 and C4 in a hospital adult population of Greater Buenos Aires / Estimativa do intervalo de referência para C3 e C4 em população adulta de um hospital da Grande Buenos Aires

El objetivo del presente trabajo fue la estimación del intervalo de referencia para los componentes del complemento C3 y C4 en población adulta hospitalaria. Se siguieron los lineamientos de la guía C28A3 de CLSI para lo cual se eligió como población de referencia a dadores de sangre concurrentes al Servicio de Hemoterapia del hospital que superaron el interrogatorio médico y accedieron a la extracción. Fue seleccionada una muestra de 251 dadores constituida por 72,9% de mujeres, de edad promedio 36,5±10 años y 27,1% de hombres, de edad promedio 40,6±11,5 años. Esta composición estuvo balanceada por sexo y edad promedio a la población de pacientes que asisten al laboratorio, en su mayoría con diagnóstico presuntivo de enfermedades autoinmunes. Los analitos fueron dosados por nefelometría cinética con nefelómetro Immage 800 de Beckman Coulter (California, EE.UU.). El intervalo de referencia se calculó por el método no paramétrico, es decir, se estimó el intervalo de confianza del 95% central de cada distribución de valores. Los límites obtenidos fueron: IC95% C3=70-165 mg/dL IC95%, C4=14-37 mg/dL. Estos resultados fueron posteriormente verificados con una serie de 20 nuevos dadores y fueron comparables a valores obtenidos en otras series citadas en la literatura.

The aim of this study was to estimate the reference interval for the components C3 and C4 complement in an adult population. The guidelines of the C28A3 document CLSI were followed, for which blood donors attending to a hospital blood centre who passed the medical examination and agreed to extraction were chosen as reference population. A sample constituted by 251 donors, 72.9% women, average age 36.5±10 years and 27.1% men, average age 40.6±11.5 years was selected. This composition was balanced by gender and average age to the population of patients attending the laboratory, mostly with autoimmune diseases. The analytes were measured by rate nephelometry with Immage 800 Nephelometer, Beckman Coulter (California, USA). The reference range for the non-parametric method was calculated, this is to say, the 95% central confidence interval of each value distribution was estimated. The limits obtained were: 95% CI C3=70-165 mg/dL and 95% CI C4=14-37 mg/dL. These results were later verified with a series of 20 new donors and are comparable to values obtained in other studies cited in the literature.

O objetivo deste estudo foi estimar o intervalo de referência para os componentes do complemento C3 e C4 na população adulta hospitalar. Foram seguidos os lineamentos do guia C28A3 de CLSI para o qual foi escolhida como população de referência doadores de sangue concorrentes do Serviço de Hemoterapia do hospital que passaram o questionário médico e acederam à extração. Foi selecionada uma amostra constituída por 251 doadores, 72,9% mulheres, com idade média de 36,5±10 anos e 27,1% dos homens de idade média 40,6±11,5 anos. Esta composição esteve equilibrada por sexo e idade média de pacientes que são atendidos no laboratório, na maioria com diagnóstico presuntivo de doenças autoimunes. Os analitos foram dosados por nefelometria cinética com nefelômetro Immage 800, Beckman Coulter (Califórnia, EUA). Calculou-se o intervalo de referência pelo método não paramétrico, quer dizer, estimou-se o intervalo de confiança de 95% central de cada distribuição de valores. Os limites obtidos foram: IC95% C3= 70-165 mg/dL e IC95% C4= 14-37 mg/dL. Estes resultados foram posteriormente verificados com uma série de 20 novos doadores e foram comparáveis a valores obtidos em outras séries citadas na literatura.

Changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia.</p><p><b>METHODS</b>Blood samples were collected from 30 children with recurrent pneumonia (recurrent pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and 30 healthy children (control group). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. The correlation between serum YKL-40 level and laboratory indices related to humoral immune function was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40 level for recurrent pneumonia.</p><p><b>RESULTS</b>The recurrent pneumonia group had a significantly higher serum YKL-40 level than the acute pneumonia and control groups (P<0.05). The acute pneumonia group had a significantly higher serum YKL-40 level than the control group (P<0.05). Serum levels of IgG and complement 4 in the recurrent pneumonia group were significantly lower than in the acute pneumonia group (P<0.05). Serum YKL-40 level was negatively correlated with serum IgG level (r=-0.309, P=0.047) and serum complement 4 level (r=-0.324, P=0.039). The area under the ROC curve of serum YKL-40 level for diagnosing recurrent pneumonia was 0.958 (95%CI: 0.921-0.994).</p><p><b>CONCLUSIONS</b>Humoral immune function is low in children with recurrent pneumonia. Serum YKL-40 may be involved in the occurrence of recurrent pneumonia and can be used as a reference index for diagnosing recurrent pneumonia.</p>

Circulating cell free DNA as a predictor of systemic lupus erythematosus severity and monitoring of therapy

Background: Systemic lupus erythematosus [SLE] is the most heterogeneous chronic autoimmune disease; it is characterized by the presence of auto reactive B and T cells, responsible for the aberrant production of a broad and heterogeneous group of autoantibodies. Recent studies using various detection methods have demonstrated the elevations of circulating DNA in SLE patients

Aim of the study: The current study aimed to measure cell-free DNA [cf-DNA] in SLE patients as a potential tool to predict disease activity and treatment follow up

Subjects and methods: 52 of SLE patients with age ranging from 10 to 48 years were randomly selected and 25 healthy subjects with age and gender matched with the patients were included as a control group. Thorough clinical examination stressing on the central nervous system, vascular, renal, rash, musculoskeletal, mucocutaneous manifestations, and fever was done for patients. The following investigations were done: Complete blood count [CBC], kidney function tests, C-reactive protein [CRP], routine autoantibodies for autoimmune diseases, complements [C3 and C4], anti-nucleosome antibodies and cf-DNA by real time PCR [RT-PCR]

Results: The levels of anti-double stranded DNA [anti-dsDNA], anti-nucleosome Ab, and cf-DNA were significantly increased in SLE patients compared to controls. The cf-DNA level was correlated to markers of disease severity namely CRP and anti-nucleosome. A significant reduction in levels of cf-DNA, anti-nucleosome Ab and anti-dsDNA was noticed after therapy

Conclusion: Our findings support that the measurement of cf-DNA appears to be a useful marker in addition to laboratory tests used in SLE diagnosis. High correlation with markers of disease severity suggesting its role in disease pathogenesis and decreasing its level after therapy makes it to be a marker of treatment follow-up

Angioedema hereditario en Medellín, Colombia: evaluación clínica y de la calidad de vida / Hereditary angioedema in Medellín (Colombia): Clinical evaluation and quality of life appraisal

Introducción. El angioedema hereditario es una inmunodeficiencia primaria de carácter autosómico dominante, debida a un déficit en la proteína inhibidora del factor C1 y caracterizada por episodios recurrentes de edema subcutáneo y de las mucosas. Las impredecibles y frecuentes crisis de angioedema afectan la calidad de vida de los individuos que las padecen. Objetivo. Analizar las características clínicas de una familia con un caso índice de angioedema hereditario y determinar el impacto de la enfermedad en la calidad de vida. Materiales y métodos. En el estudio se incluyeron 26 miembros de la familia, a 25 de los cuales se les midieron los niveles sanguíneos del factor C4 del complemento y del inhibidor de C1 antigénico y funcional. Se utilizaron dos instrumentos, el SF-36 para evaluar la salud del adulto y el KIDSCREEN-27 para la calidad de vida de niños y adolescentes. Resultados. El 83 % de los individuos que reportaron síntomas cumplían con los criterios serológicos del angioedema hereditario de tipo I: valores bajos del factor C4 del complemento y del inhibidor de C1 cuantitativo (antigénico) y cualitativo (funcional). Se encontró que la calidad de vida en cuanto al bienestar psicológico y el desempeño emocional de los pacientes, se veía considerablemente afectada por los síntomas de la enfermedad. Conclusión. Este estudio provee información sobre la primera familia caracterizada con angioedema hereditario de tipo 1 en el Valle de Aburrá, Colombia. Aunque para ello se usó un instrumento genérico, se confirmó, además, el efecto negativo de la enfermedad en la calidad de vida de los individuos que la padecen.

Introduction: Hereditary angioedema is an autosomal dominant primary immunodeficiency caused by a deficiency of the C1 inhibitor protein and characterized by recurrent episodes of subcutaneous and mucosal edema. Unpredictable and frequent crisis of angioedema affect the quality of life of individuals suffering this kind of disorder. Objective: To analyze the clinical characteristics of a family with an index case of hereditary angioedema and to determine the impact of this disease on their quality of life. Materials and methods: Twenty six members of the family were included in the trial; 25 of them were analyzed for C4 complement and antigenic and functional C1 inhibitor blood levels. Two instruments (SF-365 and KIDSCREEN-27) were used to evaluate adult health quality and children and teenagers quality of life, respectively. Results: Eighty three percent (83%) of individuals reporting symptoms of the condition exhibited serological criteria of hereditary angioedema type I: low levels of both C4 complement and quantitative (antigenic) and qualitative (functional) C1 inhibitor. In relation to patients' psychological and emotional performance, their quality of life was significantly affected by the symptoms of hereditary angioedema. Conclusion: This study provides evidence of the first family in Valle de Aburrá (Colombia) characterized as having hereditary angioedema type I. Despite the use of a generic instrument, the negative impact on the quality of life of individuals suffering this disease was also confirmed.

Clinical characteristics of children with an initial onset of IgA nephropathy with nephrotic syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of children with an initial onset of IgA nephropathy with nephrotic syndrome and compare them with children with primary nephrotic syndrome, in order to provide a theoretical basis for the differential diagnosis of the two diseases.</p><p><b>METHODS</b>Fifty children diagnosed with an initial onset of IgA nephropathy with nephrotic syndrome were included in this study. Seventy-two children diagnosed with an initial onset of primary nephrotic syndrome served as the control group. The clinical and laboratory examination characteristics were compared between the two groups.</p><p><b>RESULTS</b>The IgA nephropathy group had significantly higher incidence rates of gross haematuria, microscopic haematuria, hypertension, acute kidney injury, low serum high-density lipoprotein cholesterol, anemia, low serum complement C4, steroid resistance, and nephritis-type nephrotic syndrome and a significantly lower incidence of elevated serum IgE compared with the control group (P<0.05). There were significant differences in serum creatinine, serum uric acid, serum total cholesterol, serum high-density lipoprotein cholesterol, serum IgE, serum complement C4, and hemoglobin levels between the IgA nephropathy and the control groups (P<0.05). The thresholds of serum IgE (<131.2 IU/mL) and high-density lipoprotein cholesterol (<1.35 mmol/L) were reference parameters in the differential diagnosis of IgA nephropathy with nephrotic syndrome and primary nephrotic syndrome.</p><p><b>CONCLUSIONS</b>Children with IgA nephropathy presenting nephrotic syndrome manifest mainly as nephritis type and steroid-resistant type in the clinical classification. Cinical manifestations accompanied by serum levels of high-density lipoprotein cholesterol and IgE are helpful for differential diagnosis of IgA nephropathy presenting nephrotic syndrome and primary nephrotic syndrome.</p>

Alterations of Complement C3 and C4 Levels in Delayed Testing

BACKGROUND: In vitro levels of complement C3 and C4 proteins are sensitive to storage conditions. To avoid in vitro complement activation when testing is delayed, serum should be frozen at -20degrees C within 2 hr of venipuncture. However, this is impractical in routine laboratory work. Therefore, we investigated alterations in C3 and C4 levels in refrigerated specimens over time and derived formulae to estimate initial levels of complement concentrations in delayed testing. METHODS: Ten fresh specimens were measured for C3 and C4 concentrations and were refrigerated at 4degrees C. We measured C3 and C4 levels in refrigerated samples daily for 4 days using an automated nephelometer (Beckman Coulter Inc., USA). RESULTS: C3 and C4 levels were significantly increased over time in refrigerated specimens (P<0.001, P<0.001, respectively). The increments in C3 and C4 levels were described by the equations: C3 (mg/dL)=3.55x+87.18 (r=0.9909), and C4 (mg/dL)=0.72x+22.3 (r=0.9395), where x=the number of days samples were refrigerated before testing. Increases in C3 and C4 concentrations were described on a percentage basis by the equations: DeltaC3 (%)=4.14x+1.07 (r=0.9903), and DeltaC4 (%)=3.57x+2.48 (r=0.9405). CONCLUSIONS: As the measured C3 and C4 concentrations increased by 3.55 mg/dL (4.1%) and 0.72 mg/dL (3.6%) per day in refrigerated specimens, the levels of C3 and C4 should be adjusted in delayed testing. We proposed that the formulae presented be used to back-calculate initial levels of C3 and C4 concentrations.

Effects of rhubarb powder on serum complement 3, complement 4, and hs-CRP in patients with intracerebral hemorrhage / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effects of rhubarb powder on serum complement 3 (C3), complement 4 (C4), and hypersensitive C-reactive protein (hs-CRP) levels in patients with hypertensive intracerebral hemorrhage (HICH) after operation.</p><p><b>METHODS</b>Forty inpatients with HICH after operation were recruited from Department of Cerebral Surgery, Affiliated Hospital of Shaanxi College of Traditional Chinese Medicine from July 2009 to March 2010. They were randomly assigned to the treatment group (20 cases) and the control group (20 cases). From the 4th day after surgery, all patients received routine Western medical treatment. The rhubarb powder, 5-10 g dissolving in 40 mL warm water, was administered or nasally fed to those in the treatment group, 2 -3 times daily for 10 successive days. The contents of serum C3, C4, and hs-CRP were detected in the two groups on the 7th day and the 14th day after operation. The serum hs-CRP content was detected using latex particle enhanced immunoturbidimetric assay. The Scandinavia Stroke Scale (SSS) scores were recorded in the two groups.</p><p><b>RESULTS</b>Compared with the same group on the 4th day after operation, the levels of serum C3 and C4 increased on the 7th day after operation, and SSS score increased on the 14th day after operation in the control group (P < 0.05). The contents of C4 and hs-CRP decreased, and the SSS score increased on the 14th day after operation in the treatment group (P < 0.05). Compared with the same group on the 7th day after operation, the contents of C4 and hs-CRP decreased and the SSS score increased on the 14th day after operation in the treatment group (P < 0.05). Compared with the control group at the same time points, the contents of C4 and C3 decreased on the 7th day after operation; the contents of C3, C4, and hs-CRP decreased, and SSS score increased in the treatment group on the 14th day after operation (P < 0.05).</p><p><b>CONCLUSION</b>The rhubarb powder could significantly decrease the serum levels of C3, C4, and hs-CRP, and improve the curative effect in patients with HICH after operation.</p>

Evaluation of serum complement C3 and C4 levels as biomarkers for systemic lupus erythromatosus

Systemic Lupus Erthematosis [SLE] is a chronic autoimmune disorder that affects multiple organ systems and also affects the skin and oral mucosa, with the exact cause is unknown. Many hypotheses try to explain the role of the complement C3, C4 in the pathogenesis of SLE. The aim of this study is to determine levels of serum complement C3 and C4 in patient with SLE, so that we may explain its role in diagnosis and pathogenesis of the disease. Twenty patients were informed from outcome patients of Dermatology Unit in El-Azhar University suffering from SLE. All the patients included in this study fulfilled 4 or more of the American Rheumatism Association classification Criteria for SLE. Blood samples from These 20 SLE patients [18 females and 2 males] aged from 20 to 45 years old were collected. Complement C3 and C4 were measured using radial immunodiffusion plates system technique. Clinical parameters such as Erythrocyte Sedimentation Rate [ESR], Total Protein [TPR], Serum Creatinine and Antinuclear Antibody [ANA] of those patients were considered in order to compare and explain the data obtained for the levels of C3 and C4. The data were collected and statistically analyzed. Most of patients were female 90% and only 10% male. Of all patients, 60% have low level of serum C4, 40% have normal level of serum C4, 25% have abnormal level of serum C3, and 75% have normal level of serum C3.Statistical analysis of the data on the correlation between C4, and disease activity revealed significant [P<0.05] correlation, however no significant correlation was found between C3 and disease activity. Analysis on the correlation between C3 and C4 with TPR, S. creatinne, and ESR, showed no significant correlation. No significant relationship was also found between C3 and C4.All patients have had high TPR, S. creatinne and ESR. All patients have had positive ANA which is an important marker of SLE as an auto immune disease. Patients showed different degrees of oral and systemic manifestations, which exacerbate and become acute with decreased level of complement C4 and instability of C3 level. Accordingly, the low level of C4 was associated with the development and exacerbation of SLE. Increased C3 levels is solely due to activity through the alternative pathway in SLE patients

Reference intervals for serum immunoglobulins IgG, IgA, IgM and complements C3 and C4 in Iranian healthy children

Determination of reference ranges of each serum protein in normal population of each country is required for studies and clinical interpretation. The aim of this study was defining reference range values of immunoglobulins and complement components in Iranian healthy children. This study was conducted from June 2003 to June 2006 in Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences. Serum levels of IgG, IgM, IgA, C3 and C4 in 800 Iranian healthy children from newborn to 18 years of age in four population were measured by nephelometry. Kolmogrov-Smirnov tests and Pearson correlation tests were used for analysis. Our results mainly agree with previous reports, except for some discrepancy that might be due to the ethnic and geographic variety. There was a significant difference between two sexes only with IgA in the group of 1-3 months old, which was higher in male group and IgM in groups of 3-5, 6-8 and 9-11 years old that were higher in female groups. Mean of other serum immunoglobulins and complements was not significantly different between male and female groups. These results can be considered as a local reference for use in laboratories, clinical interpretations, and research for Iranian children

Immune function changes in patients with obstructive sleep apnea hypopnea syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the potential changes in the immune function of patients with obstructive sleep apnea hypopnea syndrome (OSAHS).</p><p><b>METHODS</b>We carried out a retrospective cross-sectional study of 187 patients with established OSAHS and 20 healthy subjects (control). For all the patients, the medical history was carefully examined, and overnight sleep monitoring was carried out with detection of the humoral and cellular immunity.</p><p><b>RESULTS</b>We found a significant increase in the levels of C3 and a decrease in both the IgM level and NK cell percentage in OSAHS patients as compared to the control group (P<0.01). Correlation analysis indicated that C3 was positive correlated to AHI but inversely to the lowest pulse oxygen saturation (LSpO(2)); IgM showed a mild positively correlation to LSpO(2), and NK cells had a mild inverse correlation to AHI. The other immunological indices were not found to undergo noticeable changes or show correlations in OSAHS.</p><p><b>CONCLUSION</b>Immune function changes occur in patients with OSAHS, characterized primarily by deteriorations in the humoral and cellular immunity.</p>

Complement components (C3, C4) as Inflammatory markers in asthma.

Objective. To assess the serum levels of complement factors C3 and C4 in Egyptian asthmatic children. Methods. This case-controlled study comprised of 60 Egyptian children with the diagnosis of bronchial asthma (not in acute attack) and 60 age-and sex-matched healthy controls. All candidates were subjected to a thorough clinical study, complete blood counts, absolute eosinophil count and serum complements (C3, C4). Results. Serum C3 was significantly higher in asthmatics when compared to controls (140.60 ± 38.80 mg/dl vs 107.70 ± 45.00 mg/dl respectively, (p = 0.01). However, differences in serum C4 levels were not significant (41.30±48.80 mg/dl vs 44.60 ± 39.70 mg/dl respectively, p = 0.69). There was a significant positive correlation between severity of asthma and serum C3 (p=0.02) but not with serum C4. Conclusions. Serum levels of C3 - but not C4 - are elevated in children with stable asthma, with a positive correlation between serum C3 and severity of asthma.