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| 2. |
- Gulez, N., et al.
(author)
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Homozygosity For a Novel Mutation in the C1q C Chain Gene in a Turkish Family With Hereditary C1q Deficiency
- 2010
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In: Journal of Investigational Allergology & Clinical Immunology. - 1698-0808. ; 20:3, s. 255-258
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Journal article (peer-reviewed)abstract
- Hereditary complete deficiency of complement component C1q is associated with a high prevalence of systemic lupus erythematosus and increased susceptibility to severe recurrent infections. An 11-year-old girl was screened for immunodeficiency due to a history of recurrent meningitis and pneumonia. Immunologic studies revealed absence of classic pathway hemolytic activity and undetectable levels of C1q. Exon-specific amplification of genomic DNA by polymerase chain reaction followed by direct sequence analysis revealed a novel homozygous missense mutation at codon 48 in the C1q C gene causing a glycine-to-arginine substitution affecting the collagen-like region of C1q. No changes were seen in the exons of the A and B chains. The mutation affected both the formation and the secretion of C1q variant molecules. We describe a novel mutation in the C1q C chain gene that leads to an interchange in amino acids resulting in absence of C1q in serum.
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| 3. |
- Hamsten, C., et al.
(author)
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Heat differentiated complement factor profiling
- 2015
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 126, s. 155-162
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Journal article (peer-reviewed)abstract
- Complement components and their cascade of reactions are important defense mechanisms within both innate and adaptive immunity. Many complement deficient patients still remain undiagnosed because of a lack of high throughput screening tools. Aiming towards neonatal proteome screening for immunodeficiencies, we used a multiplex profiling approach with antibody bead arrays to measure 9 complement proteins in serum and dried blood spots. Several complement components have been described as heat sensitive, thus their heat-dependent detectability was investigated. Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. Measurements of C7, C8 and factor I were negatively affected by heating and non-heated samples should be used in analysis of these components. In addition, a proof of concept study demonstrated the feasibility of labeling eluates from dried blood spots to perform a subsequent correct classification of C2-deficiencies. Our study demonstrates the potential of using multiplexed single binder assays for screening of complement components that open possibilities to expand such analysis to other forms of deficiencies.
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| 4. |
- Paixao-Cavalcante, Danielle, et al.
(author)
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Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation
- 2012
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 82:10, s. 1084-1092
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Journal article (peer-reviewed)abstract
- C3 nephritic factors are autoantibodies that prolong the half-life or prevent regulation of the alternative pathway C3 convertase, resulting in uncontrolled complement activation. They are strongly associated with renal disease but their role in pathogenesis remains controversial. Here we optimized and compared a panel of assays to identify and interrogate nephritic factor activities. Of 101 patients with histologic or clinically evident disease, 48 were positive in some or all assays. In the presence of properdin, binding of autoantibody was detected in 39 samples and convertase stabilization was detected in 36. Forty-two of 48 nephritic factors tested prevented convertase decay by factor H, and most of these by decay accelerating factor (28) and complement receptor 1 (34). Representative properdin-independent nephritic factors had no effect on C5 cleavage and terminal pathway activity, while properdin-dependent nephritic factors enhanced activity. Biacore analysis of four purified IgG samples confirmed resistance to decay and showed that properdin-independent nephritic factors increased convertase half-life over 50-fold, whereas properdin-dependent nephritic factors increased the half-life 10- to 20-fold and also increased activity of the C3 convertase up to 10-fold. Thus, our study provides a rational approach to detect and characterize nephritic factors in patients. Kidney International (2012) 82, 1084-1092; doi:10.1038/ki.2012.250; published online 1 August 2012
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| 5. |
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| 6. |
- Schejbel, L, et al.
(author)
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Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations
- 2011
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In: GENES AND IMMUNITY. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:8, s. 626-634
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Journal article (peer-reviewed)abstract
- C1q is the central pattern-recognition molecule in the classical pathway of the complement system and is known to have a key role in the crossroads between adaptive and innate immunity. Hereditary C1q deficiency is a rare genetic condition strongly associated with systemic lupus erythematosus and increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till now and review the clinical spectrum of symptoms found in patients with C1q deficiency. With the results presented here, confirmed C1q deficiency is reported in 64 patients from at least 38 families.
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