1.Interactions of complement proteins C1q and factor H with lipid A and Escherichia coli: further evidence that factor H regulates the classical complement pathway.
Lee Aun TAN ; Andrew C YANG ; Uday KISHORE ; Robert B SIM
Protein & Cell 2011;2(4):320-332
Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.
Binding, Competitive
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immunology
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Complement Activation
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immunology
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Complement C1q
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chemistry
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immunology
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metabolism
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Complement C4b
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analysis
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Complement Factor H
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chemistry
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immunology
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metabolism
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Complement Pathway, Classical
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immunology
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Escherichia coli
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immunology
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metabolism
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Humans
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Iodine Radioisotopes
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Isotope Labeling
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Lipid A
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immunology
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metabolism
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Liposomes
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immunology
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metabolism
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Protein Binding
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immunology
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Recombinant Proteins
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chemistry
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immunology
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metabolism
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Substrate Specificity
2.Complement activation by phospholipids: the interplay of factor H and C1q.
Lee Aun TAN ; Bingbin YU ; Francis C J SIM ; Uday KISHORE ; Robert B SIM
Protein & Cell 2010;1(11):1033-1049
Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on complement activation by aPL, we surveyed C1q and factor H binding, and complement activation by aPL, either coated on microtitre plates or in liposomes. Both C1q and factor H bound to all aPL tested, and competed directly with each other for binding. All the aPL activated the complement classical pathway, but negligibly the alternative pathway, consistent with accepted roles of C1q and factor H. However, in this system, factor H, by competing directly with C1q for binding to aPL, acts as a direct regulator of the complement classical pathway. This regulatory mechanism is distinct from its action on the alternative pathway. Regulation of classical pathway activation by factor H was confirmed by measuring C4 activation by aPL in human sera in which the C1q:factor H molar ratio was adjusted over a wide range. Thus factor H, which is regarded as a down-regulator only of the alternative pathway, has a distinct role in downregulating activation of the classical complement pathway by aPL. A factor H homologue, β2-glycoprotein-1, also strongly inhibits C1q binding to cardiolipin. Recombinant globular domains of C1q A, B and C chains bound aPL similarly to native C1q, confirming that C1q binds aPL via its globular heads.
Animals
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Complement Activation
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Complement C1q
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chemistry
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metabolism
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Complement Factor H
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metabolism
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Humans
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Immunoglobulin G
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metabolism
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Mice
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Phospholipids
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chemistry
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metabolism
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Protein Binding
3.Prevalence and risk factors of genitourinary Chlamydia trachomatis infection among patients attending sexually transmitted disease clinics in northern Malaysia
Chin Aun Yeoh ; Lee Chin Chan ; Chin Chin Ch&rsquo ; ng ; Wooi Chiang Tan
The Medical Journal of Malaysia 2020;75(2):103-109
Chlamydia trachomatis; sexually transmitted disease; prevalence;infection
Introduction: Chlamydia trachomatis is one of the most
common sexually transmitted diseases (STDs) globally.
However, data on its prevalence and risk factors in Malaysia
is still scarce.
Objective: We aimed to identify the prevalence and risk
factors of genitourinary C.trachomatis infection among
patients attending STD clinics in northern Peninsular
Malaysia.
Methods: A hospital-based cross-sectional study was
conducted in STD clinics of Hospital Pulau Pinang and
Hospital Sultanah Bahiyah, Kedah from January to
November 2014. Participants were individually interviewed
using a structured data collection form followed by a
physical examination and laboratory tests. Nucleic Acid
Amplification Test (NAAT) was used to detect C.trachomatis
infection. Analysis was carried out using SPSS Version 15.
Results: Eighty-three sexually active patients were enrolled,
consisting of 51 males and 32 females. The median age was
28.0 years. In general, 32.5% patients were asymptomatic,
the remaining presented with genital discharge (41.0%),
genital warty lesion (25.3%), genital ulcer (13.3%), dysuria
(13.3%), dyspareunia (2.4%), urine hesistancy (1.2%) and
genital swelling (1.2%). The prevalence of genitourinary
C.trachomatis infection was 21.7% in the study population;
17.6% in males and 28.1% in females. Among the infected
females, 44.4% were pregnant. Of those infected 56.6% did
not show any symptoms of genital infection, and 77.8% were
aged between 18 and 30 years, of which most were females.
Among newly diagnosed HIV patients, the prevalence was
14.3%. From multivariable logistic regression analysis, age
under 28 years, being married and engagement in oral sex
had significantly increased odds of C.trachomatis infection.
Conclusions: C.trachomatis infection was common among
patients attending STD clinics in northern Penisular
Malaysia especially in the younger age groups. Majority of
the infected patients were asymptomatic.
4.Prevalence of growth and endocrine disorders in Malaysian children with transfusion-dependent thalassaemia.
Khian Aun TAN ; Su Han LUM ; Abqariyah YAHYA ; Shekhar KRISHNAN ; Muhammad Yazid JALALUDIN ; Way Seah LEE
Singapore medical journal 2019;60(6):303-308
INTRODUCTION:
Endocrine dysfunction due to iron overload secondary to frequent blood transfusions is a common complication in children with transfusion-dependent thalassaemia (TDT). We ascertained the prevalence of endocrine dysfunction in children with TDT seen in a hospital setting in Malaysia.
METHODS:
We reviewed all patients with TDT who had ≥ 8 blood transfusions per year. Patients who had a history of stem cell transplantation, concurrent autoimmune diseases or were newly diagnosed to have TDT were excluded. Standard diagnostic criteria were used in the diagnosis of various endocrine dysfunctions.
RESULTS:
Of the 82 patients with TDT, 65% had at least one endocrine dysfunction. Short stature was the commonest (40.2%), followed by pubertal disorders (14.6%), hypoparathyroidism (12.3%), vitamin D deficiency (10.1%), hypocortisolism (7.3%), diabetes mellitus (5.2%) and overt hypothyroidism (4.9%). Subclinical hypothyroidism and pre-diabetes mellitus were seen in 13.4% and 8.6% of the patients, respectively. For children aged < 10 years, the prevalence of both thyroid dysfunction and hypoparathyroidism was 9.1%.
CONCLUSION
Two-thirds of children with TDT experienced at least one endocrine dysfunction. Thyroid dysfunction and hypoparathyroidism may be missed if endocrine screening is only performed in children with TDT > 10 years of age. Close monitoring for endocrine dysfunction and hormonal therapy is essential to prevent long-term adverse outcomes.