The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients

BACKGROUND: Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). METHODS: Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. RESULTS: CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis. CONCLUSIONS: Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.

C1 Inhibitor, C3 activator, IgG, IgA, and IgM titers in Nigerian sickle cell disease patients with plasmodium falciparum

Sickle cell disease [HbSS] is a major health problem in Nigeria and malaria has been implicated as a leading cause of morbidity/mortality in sickle cell disease patients. Few reasons were put forward to explain the observed morbidity/mortality of HbSS subjects due to Plasmodium falciparum [P. falciparum] malaria. To determine the level of immunoglobulin classes [IgM, IgA, and IgG] and regulators of complement system [C1 inhibitor and C3 activator] in Nigerian HbSS patients with and without P. falciparum parasitemia. A total of 64 subjects were considered, including 10 HbSS genotypic subjects with P. falciparum parasitemia [HbSS+PfM], 18 HbAA genotypic subjects with P. falciparum parasitemia [HbAA+PfM], 20 HbSS without P. falciparum parasitemia [HbSS-PfM], and 16 HbAA genotypic subjects without P. falciparum parasitemia [HbAA-PfM]. IgM, IgA, IgG, C1 inhibitor, and C3 activator titers were quantified by single radial immunodiffusion method. The mean levels of IgG in HbSS+PfM [2373.90 +/- 1772.81mg/dl] and HbAA+PfM [1868.80 +/- 0.00mg/dl] were significantly higher compared with HbSS-PfM [644.55 +/- 171.15mg/dl] or HbAA-PfM [659.75 +/- 158.01mg/dl] patients. HbAA-PfM subjects had the lowest level of IgM [67.27 +/- 63.7mg/dl], though no significant difference was observed comparing mean levels of IgM between the four groups. IgA titer was significantly higher in HbSS-PfM patients [249.00 +/- 94.8mg/dl] compared with HbAA-PfM [p<0.05], HbAA+PfM [p<0.05], or HbSS+PfM [p<0.05]. The mean values of C1 inhibitor were lower in HbSS+PfM and HbAA+PfM compared with HbSS-PfM or HbAA-PfM. However, HbAA+PfM had a significantly lower value of C1 inhibitor compared with HbAA-PfM [p<0.01]. C3 activator was highest in HbSS-PfM [17.10 +/- 7.35mg/dl] and was significantly higher compared with HbSS+PfM [p<0.05]. Increased C1 inhibitor and decreased C3 activator in HbSS+PfM compared with HbAA+PfM shows that deranged regulation of complement factors may be responsible for increased susceptibility of HbSS to P. falciparum malaria

Variabilidade genética dos componentes C3 e BF do sistema complemento em lúpus eritematoso sistêmico / Genetic variability of complement components C3 and BF in systemic lupus erythematosus

Objetivos - Analisar a variabilidade genética dos componentes C3 e BF do sistema complemento em pacientes brasileiros portadores de lúpus eritematoso sistêmico (LES) e as possíveis associações entre suas formas alotípicas e determinadas manifestações clínicas e laboratoriais da doença. Pacientes e métodos - O estudo foi realizado em 95 pacientes portadores de LES (88 mulheres e 7 homens, com variação etária de 14 a 57 anos, média de 30,18 anos), segundo os critérios de classificação do Colégio Americano de Reumatologia, e em 89 controles sadios. Os alótipos de C3 e de BF foram detectados no soro dos pacientes e controles através de eletroforese de alta voltagem em gel agarose, seguido de imunofixação com anticorpo específico. Resultados - Os alótipos de C3 e BF observados no presente estudo foram: C3S, C3F, C3SF, C3SS05 e BFS, BFF, BFSSF, BFSF1, BFSF075, BFSS07, BFF1. Os resultados obtidos demonstrarem aumento do alótipo BFF nos pacientes, quando comparados com os controles normais (p= 0,055; RR = 2,87); para os demais alótipos, não houve diferença signifiante quanto à sua distribuição. Menor frequência do alótipo BFS foi observada nos pacientes que apresentaram manifestações neurológicas, em relação aos que não as tiveram (p=0,059); RR = 0,28). Também nos pacientes que apresentaram serosites, observou-se frequência diminuída dos alótipos C3S e BFS, quando comparados com os que naõ apresentaram esta manifestação durante o curso da doença (p=0,036 para C3 e p=0,021 para BF; RR = 0,38 para ambos). Conclusões - A frequência diminuída de BFS nos pacientes com manifestações neurológicas e de C3S e BFS nos que apresentaram serosites no curso da doença sugere associação negativa e possível papel protetor desses alótipos no desenvolvimento dessas manifestações clínicas no LES. Os achados aqui descritos sugerem que a variabilidade genetica das proteínas C3 e BF do sistema complemento pode estar relacionada com o mecanismo etiopatogênico e com a expressão clínica do LES em pacientes brasileiros

Immunoglobulin and C3-activator profile of the microbiology laboratory worker.

The levels of immunoglobulin, C3-Activator and C3c in the sera of members of staff who have been continuously engaged for upwards of 10 years in the microbiological routine laboratory of a teachings hospital were determined. These were compared with the local normals, with those of the junior members of staff in the same laboratory but who had put in less than 5 years continuous service and with a control group. The means in all five determinations were much higher in the senior members of staff than the normal standards of the area, particularly the IgG, which was almost double the local normals. The levels for the junior staff were on the whole slightly higher than the control group. The increase in the levels of immunoglobulins with corresponding increases in C3-Activator and 3Cc suggest that immunological reactions, with the binding of complement in the alternate and classical pathways of activation are taking place in most of these senior workers. In the absence of any manifest illness in the senior staff, the findings may suggest a high degree of immunological protection.

Alteraciones del sistema complemento en el mieloma multiple / Alterations of the complement system in myeloma

Se efectuó la medición de la actividad de la vía clásica y alternativa, la actividad funcional del factor B y factor D, la cuantificación de C3 y C4, así como la detección de inmunocomplejos circulantes, en 23 pacientes con mieloma múltiple. Se observó una disminución estadísticamente significativa de la actividad de la vía alternativa, el factor B y bajos niveles de C3; el resto de los parámetros estudiados se mantuvo dentro de los límites normales. Los resultados obtenidos sugieren un fallo al nivel del mecanismo de activación de la vía alternativa debido a posibles alteraciones de sus componentes individuales, hecho a su vez favorecedor de la alta susceptibilidad a las infecciones en estos pacientes

Ascitic fluid C3 and opsonic activity in endemic liver cirrhosis

This study was conducted on 30 patients with endemic liver cirrhosis and ascitis with symptoms suggestive of spontaneous bacterial peritonitis [SBP]. Ascitic fluid culture was positive in 19 cases [Group [I]] while no growth could be detected In 11 cases [Group [II]]. Correlation studies between the various parameters of ascitic fluid showed that :1] The total leucocytic count and LDH levels were significantly higher in group [I] [culture. positive] than in group [II] [culture negative], while the protein level did not show any significant difference between both groups. 2] C[3] was significantly lower in group [I] compared to group [II]. Also, serum C[3] was found to be significantly lower in patients with liver cirrhosis compared to normal control sera. 3] The opsonic activity of ascitic fluid in group[I] was significantly lower than group [II]

C3: a versatile and multifunctional complement protein

The major complement component, C3, is the substrate for C3 convertases which emerge by activation of the classical and alternative complement pathways; fragments C3b and C3a are the resulting split products. The C3b becomes a constituent of the amplification C3-convertase in the alternative pathway, and of the C5 convertases responsible for the organization of the potentially cytolytic complex C5b-C9, being also able to interact with numerous serum proteins, cell surface molecules and foreign protein. The C3a functions as mediator of the early events of teh inflamatory process. Recent observations on the molecular features involved in the multiple interaction of C3 characterize this proteins as a most versatile and multifunctional molecule which is also an important participant of both the immune and monimmune surveillance mechanism

Evasion of Trypanosoma cruzi from complement lysis

This review outlines: a) the main biochemical and biological properties of the complement system (C) componentes; b) the manner through which they interact in the two distinct routes of C activation, the classical and the alternative pathways, to generate the enzymes C3 and C5 convertases responsible for release of the peptides C4a, C3a and C5a endowed with the properties of mediating the early events of the inflammatory process or the potentially cytolytic complex C5b-C9; c) the main features of control of these activation processes; d) the identification of cell surface components present in the trypomastigote forms of Trypanosoma cruzi possibly involved in the mechanisms developed by this parasite to evade C lysis; e) the inactivation or removal of these cell surface components by enzymatic (trypsin or papin), chemical (periodate) or physical (heating at 45-C) treatments; f) isolation of these components by chromatographic methods; and, g) demonstration that some of these cell surace components interfere with C3 convertase formation or action in a manner similar to the decay accelerating factor (DAF)

Complemento hemolitico total, C3 e taxa de conversao de C3 nas formas cardiaca e indeterminada da Doenca de Chagas. / Total hemolytic complement, C3 and C3 convertase levels in cardiac and indeterminate forms of Chagas' disease

Os valores de complemento hemolitico total C3 total (nativo + produtos de degradacao) e o grau de conversao de C3 nativo foram estudados em dois subgrupos de pacientes chagasicos, nas formas cardiaca e indeterminada, e em um subgrupo de individuos nao chagasicos, clinicamente sadios.Os niveis de C3 total e as taxas de conversao de C3 em seus produtos de degradacao foram semelhantes nos tres subgrupos. Os valores de complemento hemolitico total foram estatisticamente diferentes nos tres subgrupos (nivel de significancia descritivo p= 0,0757), tendo sido observada media aritmetica mais baixa no subgrupo de cardiacos e mais elevada no subgrupo de controles.Maior amplitude de variacao dos niveis de complemento hemolitico total foi notada no subgrupo de cardiacos, no qual se encontraram os valores extremos (maximo e minimo), considerando-se todos os subgrupos

Conversion of the C3 component of complement in sera of hanseniasis patients.

Os niveis de C3 total (C3 nativo mais seus produtos de degradacao) e o grau de conversao do C3 nativo em seus produtos de degradacao foram estudados em soros de pacientes V, T, I e de V com ENH. Soros de individuos normais foram tambem analisados, enquanto os niveis de C3 total nao diferiram significativamente entre os grupos, a conversao de C3 em seus produtos de degradacao foi significativamente maior nos soros de pacientes V e naqueles com ENH. A ativacao do sistema complemento e o envolvimento dos IC neste processo sao discutidos