• Childhood Kidney Diseases
• /
• 제23권1호
• /
• pp.43-47
• /
• 2019

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 (antiCFH-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.

• Journal of Microbiology and Biotechnology
• /
• 제10권2호
• /
• pp.267-271
• /
• 2000

Abstract Two glucans (PONGa and PONGb) differing in their anomeric and glycosidic linkage structures were isolated from the water-insoluble materials (PON) of Pleurotus ostreatus basidiocarps, which activated the complement system and were almost soley composed of D-glucose. The isolatIon was achieved by repeated precipitations with ethanol and adsorption on concanavalin A (Con A) of paN suspension in thymol/NaCL Based on methylation analysis. IR, GLC-MS, $^1H,{\;}and{\;}^{13}C-NMR$ spectroscopies, PONGa was found to be a branched a-glucan composed of ${\alpha}-linked$ D-glucopyranose residues and ${\alpha}-linked$ units with 6-branching points, whereas PONGb was a linear ${\beta}-1,3-glucan$ composed mainly of ${\beta}-1,3-linked$ D-glucopyranose residues. The PONGb particles reacted more potently than the PONGa particles as C3 activator in alternative complement hemolysis and crossed-immunoelectrophoresis using anti-human C3, thereby suggesting that the complement activating components of PON were ${\beta}-(13)-glucans rather$ than ${\alpha}-glucan$ components.onents.

• Asian-Australasian Journal of Animal Sciences
• /
• 제28권9호
• /
• pp.1354-1361
• /
• 2015

The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative) leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs) in pigs of the breeds Hampshire (HS), Duroc (DU), Berlin miniature pig (BMP), German Landrace (LR), Pietrain (PIE), and Muong Khuong (Vietnamese potbelly pig). Genotyping was performed in 417 $F_2$ animals of a resource population (DUMI: $DU{\times}BMP$) that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE) show higher allele frequency of these SNPs than Vietnamese porcine breed (MK). Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9) as a candidate gene to improve general animal health in the future.

• 한국식품과학회지
• /
• 제34권2호
• /
• pp.290-295
• /
• 2002

김치 및 발효유 제품으로부터 분리한 유산균과 공시균주 12종을 대상으로 보체 용혈 분석법을 이용하여 면역계에서 중요한 역할을 담당하고 있는 보체계 활성화(항보체 활성, $TCH_{50}$) 정도를 측정한 결과, 김치로 부터 분리한 Lactobacillus plantarum이 타 유산균 종에 비해 높은 활성을 나타내었다. 이들 균주로 부터 조제된 세포벽 획분의 경우 세포질 획분보다도 높은 활성을 보였으며 각 획분의 활성은 농도 의존적 경향을 나타내었다. L. plantarum의 세포질 획분과 세포벽 획분의 경우 pronase 소화 후에는 활성의 변화가 없는 반면, 과요오드산 처리에 의해서는 급격한 활성의 감소를 나타내는데 이들 결과로부터 L. plantarum의 세포질과 세포벽 획분에 의한 보체계 활성화가 주로 다당 영역에 기인함을 알수 있었다. 한편 anti-human C3를 이용한 2차원 면역전기영동에 의해, $Ca^{++}$ 이온을 제거한 상태에서도 세포질과 세포벽 획분에 의한 C3 활성화 산물을 동정할 수 있었다. 또한 L. plantarum의 세포벽 획분에 의한 항보체 활성은 동일 조건에서 활성을 유지한 반면, 세포질 획분에 의한 활성화 정도는 동일 조건에서 상당히 감소하였다. 이상의 결과로부터 L. plantarum 세포벽 획분의 보체계 활성화 양식은 주로 alternative pathway의 활성화에 의한 것이며, 세포질 획분에 의한 활성화는 classical pathway와 alternative pathway 양 경로를 경유함을 알 수 있었다.

• 한국미생물학회:학술대회논문집
• /
• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
• /
• pp.23-25
• /
• 2008

Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

• Childhood Kidney Diseases
• /
• 제23권2호
• /
• pp.93-99
• /
• 2019

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.

• Applied Biological Chemistry
• /
• 제39권2호
• /
• pp.147-152
• /
• 1996

천연으로부터 보체 저해활성 물질을 선발할 목적으로 용혈성 보체측정법(hemolytic complement assay, $CH_{50}$)을 이용한 미량 탐색법을 확립하였다. 보체결합 반응은 microplate에서 수행하였으며, 표준 용혈(50% hemolysis)을 설정하기 위한 최적조건은 classical pathway (CP)의 경우 양 적혈구 농도를 $5.0{\times}10^8\;cells/ml$로 하였을때 hemolysin 희석농도 $1/75{\sim}1/100$ 및 보체 희석농도 $1/80{\sim}1/120$이었으며, alternative pathway (AP)의 경우는 토끼 적혈구 농도 $4.0{\times}10^8\;cells/ml$에서 보체 희석농도 l/5, EGTA 4mM 및 $Mg^{2+}\;4{\sim}8mM$ 이었다. 비수용성 화합물의 검정에는 dimethyl sulfoxide를 1% 수준이 되도록 시료의 농도를 조절하여 첨가하였다. 본 실험 조건에서 3종의 phenylpropanoid는 모두 농도에 비례하여 항보체 활성을 나타내었는데, 그중 rosmarinic acid의 항보체 활성은 CP의 경우 $0.063{\sim}0.5mM$에서 $5.4{\pm}3.6%{\sim}95.8{\pm}0.2%$, AP의 경우 $0.063{\sim}1\;mM$에서 $35.1{\pm}0.9%{\sim}95.6{\pm}1.1%$으로 측정되었다.

• 한국식품영양학회지
• /
• 제9권4호
• /
• pp.490-495
• /
• 1996

홑파래로부터 황산기를 함유한 다당체를 크로마토그래프로 분리정제하여 rhamnan sulfate가 항보체 활성화에 미치는 영향을 조사하였다. 항보체 활성능력은 F-4-3 획분을 비교군으로 Heparin H-180, Dextran과 비교해 결과 비교군보다 높았고, C4a와 C3a의 C convertase의 형성과 기능을 F-4-3 획분이 억제하였다. 이러한 보체 활성화 양식은 classical pathway 및 alternative pathway로도 경유함을 알 수 있었다.

• Clinical and Experimental Pediatrics
• /
• 제50권10호
• /
• pp.931-937
• /
• 2007

The hemolytic uremic syndrome (HUS) is a rare disease of microangiopathic hemolytic anemia, low platelet count and renal impairment. HUS usually occurs in young children after hemorrhagic colitis by shigatoxin-producing enterohemorrhagic E. coli (D+HUS). HUS is the most common cause of acute renal failure in infants and young children, and is a substantial cause of acute mortality and morbidity; however, renal function recovers in most of them. About 10% of children with HUS do not reveal preceding diarrheal illness, and is referred to as D- HUS or atypical HUS. Atypical HUS comprises a heterogeneous group of thrombomicroangiopathy (TMA) triggered by non-enteric infection, virus, drug, malignancies, transplantation, and other underlying medical condition. Emerging data indicate dysregulation of alternative complement pathway in atypical HUS, and genetic analyses have identified mutations of several regulatory genes; i.e. the fluid phase complement regulator Factor H (CFH), the integral membrane regulator membrane cofactor protein (MCP; CD46) and the serine protease Factor I (IF). The uncontrolled activation of the complement alternative pathway results in the excessive consumption of C3. Plasma exchange or plasma infusion is recommended for treatment of, and has dropped the mortality rate. However, overall prognosis is poor, and many patients succumb to end-stage renal disease. Clinical presentations, response to plasma therapy, and outcome after renal transplantation are influenced by the genotype of the complement regulators. Thrombotic thrombocytopenic purpura (TTP), another type of TMA, occurs mainly in adults as an acquired disease accompanied by fever, neurologic deficits and renal abnormalities. However, less frequent cases of congenital or hereditary TTP associated with ADAMTS-13 (a disintegrin and metalloprotease, with thrombospondin 1-like domains 13) gene mutations have been reported, also. Recent advances in molecular genetics better allow various HUS to be distinguished on the basis of their pathogenesis. The genetic analysis of HUS is important in defining the underlying etiology, predicting the genotype-related outcome and optimizing the management of the patients.

• Applied Biological Chemistry
• /
• 제35권6호
• /
• pp.462-469
• /
• 1992

대복피(빈랑나무의 과피)로부터 면역조절 역할이 기대되는 2종의 보체활성화(항보체) 다당을 정제하고 그 작용양식에 대해 검토하였다. 활성다당 AC-2-IIIa 및 AC-2-IIIc는 농도가 증가함에 따라 항보체 활성이 증가하는 양상을 보였으며, 2가 금속이온 부재시 대조구에 비해 거의 완전한 활성의 감소를 보인 반면, $Ca^{2+}$ 이온만을 선택적으로 제거한 경우 활성이 상당량 유지되었다. 또한 이들 활성다당들은 비교적 강력한 보체 제 2경로 활성화능을 나타내었으며, $Ca^{2+}$ 이온 부재 상태에서 정상인의 혈청과 반응시, C3의 분해산물을 anti-human C3를 이용한 면역 전기영동법에 의해 확인할 수 있었다. 또한 anti-human whole serum를 이용한 면역 전기영동 결과, ${\alpha}2-M$ peak 대비 3rd peak의 높이 비율은 AC-2-IIIa가 $1.50{\pm}0.04$, AC-2-IIIc가 $1.22{\pm}0.08$이었는바, 이러한 사실로부터 대복피 유래 AC-2-IIIa 및 AC-2-IIIc의 보체 활성화 양식은 classical 및 alternative pathway 양경로를 모두 경유함을 알 수 있었다.