Complement haemolytic activity (classical and alternative pathways), C3, C4 and factor B titres in healthy children

Ferriani, Virgínia Paes Leme; Barbosa, José Elpídio; Carvalho, Ivan Fiore de

doi:10.1111/j.1651-2227.1999.tb00988.x

Cited by 22 publications

(5 citation statements)

References 13 publications

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“…While complement components are already synthesized early in fetal life, the complement activity in newborns seems to be lower than in adults ( 54 ). It has been reported that the C1q and properdin levels are low and fB levels are high in children between 1-5 years ( 55 ) and that the concentration of complement proteins C3 and C4 is constant in children under 18 years ( 56 ). The reported generally reduced complement activity may contribute to the higher susceptibility of newborns and infants to invasive infection by various encapsulated bacteria.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the different complement pathways has varying impacts on the serum bactericidal activity and opsonophagocytosis against Haemophilus influenzae type b

et al. 2022

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Defense against Haemophilus influenzae type b (Hib) is dependent on antibodies and complement, which mediate both serum bactericidal activity (SBA) and opsonophagocytosis. Here we evaluated the influence of capsule-specific antibodies and complement inhibitors targeting the central component C3, the alternative pathway (AP; fB, fD), the lectin pathway (LP; MASP-2) and the terminal pathway (C5) on both effector functions. Findings may be relevant for the treatment of certain diseases caused by dysregulation of the complement system, where inhibitors of complement factors C3 or C5 are used. Inhibitors against other complement components are being evaluated as potential alternative treatment options that may carry a reduced risk of infection by encapsulated bacteria. Serum and reconstituted blood of healthy adults were tested for bactericidal activity before and after vaccination with the Hib capsule-conjugate vaccine ActHIB. Most sera had bactericidal activity prior to vaccination, but vaccination significantly enhanced SBA titers. Independently of the vaccination status, both C3 and C5 inhibition abrogated SBA, whereas inhibition of the LP had no effect. AP inhibition had a major inhibitory effect on SBA of pre- vaccination serum, but vaccination mitigated this inhibition for all disease isolates tested. Despite this, SBA-mediated killing of some Hib isolates remained retarded. Even for the most serum-resistant isolate, SBA was the dominating defense mechanism in reconstituted whole blood, as addition of blood cells to the serum did not enhance bacterial killing. Limited Fc receptor-mediated opsonophagocytosis was unmasked when bacterial killing by the membrane attack complex was blocked. In the presence of C3 or C5 inhibitors, addition of post-vaccination, but not of pre-vaccination serum to the blood cells triggered opsonophagocytosis, leading to suppression of bacterial multiplication. Taken together, our data indicate that for host defense against Hib, killing by SBA is more efficient than by blood cell opsonophagocytosis. However, additional defense mechanisms, such as bacterial clearance by spleen and liver, may play an important role in preventing Hib-mediated sepsis, in particular for Hib isolates with increased serum-resistance. Results indicate potentially improved safety profile of AP inhibitors over C3 and C5 inhibitors as alternative therapeutic agents in patients with increased susceptibility to Hib infection.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the different complement pathways has varying impacts on the serum bactericidal activity and opsonophagocytosis against Haemophilus influenzae type b

et al. 2022

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“…The lytic complement activity of CP and AP was measured by means of a kinetic assay, as previously described, with minor modifications. 7,8 Briefly, the time required to lyse 50% of an erythrocyte suspension was measured (T1/2). Low T1/2 values for CP and AP correlate with high CP and AP complement activities, respectively.…”

Section: Methodsmentioning

confidence: 99%

Complement Levels in Brazilian Children During and After Meningococcal Meningitis

Júnior¹,

Ferriani²,

Teixeira³

et al. 2005

Clinics

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ROXO Jr. P et al. Complement levels in Brazilian children during and after meningococcal meningitis. CLINICS 60(2):127-130, 2005. PURPOSE:To evaluate the functional activity of the classical and alternative pathways of the complement system and the levels of C3, C4, and factor B during the first episode of meningococcal infection and during the convalescence period.PATIENTS AND METHODS: Ten Brazilian children ranging in age from 8 months to 8 years, admitted from 1991 to 1993 with a clinical-laboratory diagnosis of meningococcal meningitis, were studied during acute infection (up to 7 days from diagnosis) and during the convalescence period (1 to 6 months after the acute episode). C3, C4, and Factor B were measured using nephelometry, and the lytic activity of classical and alternative pathways were evaluated by a kinetic method and expressed as the time needed to lyse 50% of an erythrocyte suspension (T1/2, expressed in seconds). Low T1/ 2 values for classical and alternative pathways correlate with high activities of the classical and alternative complement pathways, respectively.RESULTS: A significant difference was observed between the alternative pathway lytic activity during infection and the convalescence period (282 vs 238 seconds, respectively, P = .01). No differences were detected in the other complement parameters analyzed.CONCLUSIONS: In the presence of meningococcal meningitis, the alternative pathway is preferentially activated. This is probably due to the greater ability of the meningococcal endotoxin to activate this pathway in vivo.

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“…Seroprevalence studies in the United Kingdom (4-7) confirmed a decline in meningococcal disease without a corresponding increase in the proportion of individuals with higher SBA titers. This indicates that alternative mechanisms of protection must be responsible and may include the age-related maturation of the alternative complement pathway (8,9), the presence of bactericidal activity in blood as observed using whole-blood killing assays (10,11), opsonic activity (12), or a combination of these activities. Immunization with a serogroup B outer membrane vesicle (OMV) vaccine, alone or in combination with recombinant antigens, has also been shown to elicit antibodies that have opsonophagocytic killing activity despite SBA titers being Ͻ1:4 (12).…”

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confidence: 99%

Seroprevalence of Antibody-Mediated, Complement-Dependent Opsonophagocytic Activity against Neisseria meningitidis Serogroup B in England

Humphries¹,

Brookes²,

Allen³

et al. 2015

Clin. Vaccine Immunol.

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The correlate of protection for the licensure of meningococcal vaccines is serum bactericidal activity. However, evidence indicates that a complex situation and other mechanisms, such as antibody-mediated, complement-dependent opsonophagocytosis (OP), may play a role in protection and should be investigated in order to understand immunity to this disease. In this study, a high-throughput flow cytometric opsonophagocytic assay (OPA) was optimized. The assay measures the presence of killed fluorescently labeled Neisseria meningitidis within human granulocytes (differentiated HL60 cells) by flow cytometry, using IgGdepleted pooled human plasma as an exogenous source of complement. This method was found to be reliable and correlated with the results of an opsonophagocytic killing assay. The OPA was used to measure OP activity in 1,878 serum samples from individuals ranging from 0 to 99 years of age against N. meningitidis strain NZ98/254 (B:4:P1.7-2,4). The levels of OP activity in individual serum samples varied greatly. OP activity showed an initial peak in the 6-to 12-month age group corresponding to a peak in disease incidence. The OP activity dropped in childhood until the late teenage years, although there was still a higher percentage of individuals with OP activity than with protective bactericidal antibody titers. OP activity reached a peak in the 30-to 39-year age group and then declined. This later peak in OP activity did not coincide with the young adults in whom peak serum bactericidal activity and disease incidence occurred. The demonstration of OP activity when disease incidence is low and when protective bactericidal antibody titers are not detected may indicate a role for OP in protection from meningococcal disease in these age groups.T he correlate of protection for the licensure of meningococcal vaccines is serum bactericidal activity, as measured by the serum bactericidal assay (SBA). This was established by direct evidence obtained in studies carried out in the 1960s by Goldschneider (1), who observed an epidemic of serogroup C meningococcal disease in military recruits. In this study, while 82% of the military recruits had SBA titers of Ն1:4 at the start of their basic training, 51 out of 53 recruits who developed meningococcal disease had SBA titers of Ͻ1:4 against the epidemic strain. Thus, it was proposed that a titer of Ն1:4 conferred protection against disease (1). In a concurrent paper by Goldschneider (2), it was also observed that SBA titers of Ն1:4 were rarely observed in children between 6 and 12 months of age, which is the age group with the highest incidence of meningococcal disease.However, there is evidence to suggest that protection from meningococcal disease is possible even in the absence of an SBA titer of Ն1:4 (reviewed by Granoff [3]). Even in the initial reports by Goldschneider (1, 2), it was noted that there were many recruits who were likely to have been exposed to the epidemic strain and had SBA titers of Ͻ1:4 but did not develop meningococcal disease (1). Therefore, wh...

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Complement haemolytic activity (classical and alternative pathways), C3, C4 and factor B titres in healthy children

Cited by 22 publications

References 13 publications

Inhibition of the different complement pathways has varying impacts on the serum bactericidal activity and opsonophagocytosis against Haemophilus influenzae type b

Inhibition of the different complement pathways has varying impacts on the serum bactericidal activity and opsonophagocytosis against Haemophilus influenzae type b

Complement Levels in Brazilian Children During and After Meningococcal Meningitis

Seroprevalence of Antibody-Mediated, Complement-Dependent Opsonophagocytic Activity against Neisseria meningitidis Serogroup B in England

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