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Fragment Bb: evidence for activation of the alternative pathway of the complement system in pregnant women with acute pyelonephritis.

ABSTRACT: OBJECTIVE:Pyelonephritis during pregnancy is associated with a more severe course than in the non-pregnant state. This has been attributed to an increased susceptibility of pregnant women to microbial products. The complement system is part of innate immunity and its alternative pathway is activated mainly by microorganisms. The purpose of this study was to determine if activation of the alternative pathway of the complement system (determined by maternal fragment Bb concentrations) occurs in pregnant women with acute pyelonephritis. METHODS:This cross-sectional study included the following groups: (1) normal pregnant women (n=62) and (2) pregnant women with pyelonephritis (n=38). Maternal plasma fragment Bb concentrations were determined by ELISA. Non-parametric statistics were used for analyses. RESULTS:(1) Pregnant women with pyelonephritis had a higher median plasma concentration of fragment Bb than those with a normal pregnancy (1.3??g/ml, IQR: 1.1-1.9 vs. 0.8??g/ml, IQR: 0.7-0.9; p<0.001); (2) No significant differences were observed in the median maternal plasma concentration of fragment Bb between pregnant women with pyelonephritis who had a positive blood culture and those with a negative blood culture (1.4??g/ml, IQR: 1.1-3.5 vs. 1.3??g/ml, IQR: 1.1-1.9; p=0.2). CONCLUSIONS:Pregnant women with acute pyelonephritis have evidence of activation of the alternative pathway of the complement system, regardless of the presence or absence of a positive blood culture.

SUBMITTER: Soto E

PROVIDER: S-EPMC2941983 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Fragment Bb: evidence for activation of the alternative pathway of the complement system in pregnant women with acute pyelonephritis.

Soto Eleazar E Romero Roberto R Vaisbuch Edi E Erez Offer O Mazaki-Tovi Shali S Kusanovic Juan Pedro JP Dong Zhong Z Chaiworapongsa Tinnakorn T Yeo Lami L Mittal Pooja P Hassan Sonia S SS

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 20101001 10

<h4>Objective</h4>Pyelonephritis during pregnancy is associated with a more severe course than in the non-pregnant state. This has been attributed to an increased susceptibility of pregnant women to microbial products. The complement system is part of innate immunity and its alternative pathway is activated mainly by microorganisms. The purpose of this study was to determine if activation of the alternative pathway of the complement system (determined by maternal fragment Bb concentrations) occu ...[more]

PMID: 20218820

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Project description:The innate immune system plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently we reported complement activation in human NASH. However, it remained unclear whether the alternative pathway of complement, which amplifies C3 activation and which is frequently associated with pathological complement activation leading to disease, was involved. Here, alternative pathway components were investigated in liver biopsies of obese subjects with healthy livers (n = 10) or with NASH (n = 12) using quantitative PCR, Western blotting, and immunofluorescence staining. Properdin accumulated in areas where neutrophils surrounded steatotic hepatocytes, and colocalized with the C3 activation product C3c. C3 activation status as expressed by the C3c/native C3 ratio was 2.6-fold higher (p<0.01) in subjects with NASH despite reduced native C3 concentrations (0.94±0.12 vs. 0.57±0.09; p<0.01). Hepatic properdin levels positively correlated with levels of C3c (rs = 0.69; p<0.05) and C3c/C3 activation ratio (rs = 0.59; p<0.05). C3c, C3 activation status (C3c/C3 ratio) and properdin levels increased with higher lobular inflammation scores as determined according to the Kleiner classification (C3c: p<0.01, C3c/C3 ratio: p<0.05, properdin: p<0.05). Hepatic mRNA expression of factor B and factor D did not differ between subjects with healthy livers and subjects with NASH (factor B: 1.00±0.19 vs. 0.71±0.07, p = 0.26; factor D: 1.00±0.21 vs. 0.66±0.14, p = 0.29;). Hepatic mRNA and protein levels of Decay Accelerating Factor tended to be increased in subjects with NASH (mRNA: 1.00±0.14 vs. 2.37±0.72; p = 0.22; protein: 0.51±0.11 vs. 1.97±0.67; p = 0.28). In contrast, factor H mRNA was downregulated in patients with NASH (1.00±0.09 vs. 0.71±0.06; p<0.05) and a similar trend was observed with hepatic protein levels (1.12±0.16 vs. 0.78±0.07; p = 0.08). Collectively, these data suggest a role for alternative pathway activation in driving hepatic inflammation in NASH. Therefore, alternative pathway factors may be considered attractive targets for treating NASH by inhibiting complement activation.

Dataset Information

Fragment Bb: evidence for activation of the alternative pathway of the complement system in pregnant women with acute pyelonephritis.

Publications

Fragment Bb: evidence for activation of the alternative pathway of the complement system in pregnant women with acute pyelonephritis.

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