Hereditary Human Complement C3 Deficiency Owing to Reduced Levels of C3 mRNA

Ulbrich, A. G.; Florido, M.P.C.; Nudelman, Victor; Baracho, Gisele V.; Isaac, Lourdes

doi:10.1046/j.1365-3083.2001.00934.x

Cited by 16 publications

(13 citation statements)

References 22 publications

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“…In line with the concept that C3dg acts as adjuvant in the activation of B cells and antibody production, differential ability in mounting antibody responses toward specific antigens after vaccination of C3‐deficient patients has previously been reported . Furthermore, extremely low levels of total IgG4 have been determined in some of the patients . In addition, recent reports have described impaired T‐ and B‐cell responses ex vivo when lymphocytes from C3‐deficient patients are used .…”

Section: Too Much Too Little: Disturbed C3 Balance and Its Clinical mentioning

confidence: 61%

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

352

295

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Summary As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target.

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Section: Too Much Too Little: Disturbed C3 Balance and Its Clinical mentioning

confidence: 61%

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

352

295

View full text Add to dashboard Cite

show abstract

“…1; Table 1). This weak radial lysis was not observed for a complement-deficient serum sample with undetectable C3 and a normal fB concentration (P2 sera) (18) or with sera from patients with low fB levels and residual C3 levels (P3 sera) or undetectable C3 levels (P4 sera) ( Fig. 1; Table 1).…”

Section: Resultsmentioning

confidence: 88%

“…On the other hand, primary C3-deficient patients have little C3 or completely lack of C3 but have normal levels of fB, fH, and fI (18,19). Impairment of the complement-dependent functions is observed in patients with both primary and secondary C3 deficiencies.…”

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confidence: 99%

Simple Method To Distinguish between Primary and Secondary C3 Deficiencies

Florido

Paula

Isaac

2003

Clin Vaccine Immunol

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Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent infections; and the application of easy, reliable, and low-cost methods for their detection and distinction are always welcome, notably in developing countries. When activation of the alternative complement pathway is evaluated in hemolytic agarose plates, some but not all human sera cross-react to form a late linear lysis. Since the formation of this linear lysis is dependent on C3 and factor B, it is possible to use late linear lysis to routinely screen for the presence of deficiencies of alternative human complement pathway proteins such as factor B. Furthermore, since linear lysis is observed between normal human serum and primary C3-deficient serum but not between normal human serum and secondary C3-deficient serum caused by the lack of factor H or factor I, this assay may also be used to discriminate between primary and secondary C3 deficiencies.The human complement system is formed by more than 30 proteins and plays several important inflammatory and immune functions derived from its activation (10). Complement can be activated by the classical, alternative, and lectin pathways. The activation of the alternative complement pathway occurs at a slow but constant rate and is initiated by the hydrolysis of an internal thioester bond in C3 that leads to the formation of C3(H 2 O) (12). When factor B (fB) binds to C3(H 2 O), it is cleaved by factor D (fD), generating the first C3 convertase of the alternative pathway, C3(H 2 O)Bb, which cleaves C3 to C3a and C3b. C3b binding to fB, followed by cleavage by fD, generates the second C3 convertase of the alternative pathway, C3bBb. As a consequence, several molecules of C3 are cleaved to C3a and C3b in a short period of time. If this activation is not properly regulated, C3 is converted into C3b and a marked consumption of C3 is observed (secondary deficiency) (1,2,19).Factor I (fI) is one of the most important C3 regulatory proteins since it cleaves C3b to iC3b, which is subsequently cleaved by fI to produce C3c and C3d. fI requires the presence of several cofactor proteins, principally, factor H (fH), to perform its regulatory functions properly.Sera from individuals with homozygous deficiencies of fI or fH or from individuals presenting with nephritic factors have very low levels of intact C3 and low levels of fB (2,7,11,19). On the other hand, primary C3-deficient patients have little C3 or completely lack of C3 but have normal levels of fB, fH, and fI (18,19). Impairment of the complement-dependent functions is observed in patients with both primary and secondary C3 deficienc...

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“…Serum samples from twelve controls and the Swedish [20] and Brazilian patients [21] were analysed for C3 levels by ELISA and serum microarrays. No C3 was detected in the two C3 deficient patient samples, whereas both methods readily detected C3 in all twelve control serum samples (varying from 0.7 to 1.2 g/l), with a correlation of 0.83 (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…A serum sample from an adult Brazilian C3 deficient patient [21] was collected at Laboratory of Complement, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil and lyophilized. Before use this C3 deficient serum was reconstituted in 100 µl of PBS.…”

Section: Methodsmentioning

confidence: 99%

Screening for C3 Deficiency in Newborns Using Microarrays

et al. 2009

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BackgroundDried blood spot samples (DBSS) from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods.Methodology/Principal FindingsWe have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients.Conclusions/SignificanceThe findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.

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Hereditary Human Complement C3 Deficiency Owing to Reduced Levels of C3 mRNA

Cited by 16 publications

References 22 publications

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Simple Method To Distinguish between Primary and Secondary C3 Deficiencies

Screening for C3 Deficiency in Newborns Using Microarrays

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