Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies

Sissy, Carine El; Rosain, Jérémie; Vieira-Martins, Paula; Bordereau, Pauline; Gruber, Aurélia; Devriese, Magali; Pontual, Loïc de; Taha, Muhamed‐Kheir; Fieschi, Claire; Pïcard, Capucine; Frémeaux‐Bacchi, Véronique

doi:10.3389/fimmu.2019.01936

Cited by 43 publications

(34 citation statements)

References 52 publications

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“…Although the dysmorphic C6 protein still has certain residual activity (9), the truncated C6 protein in the present study is expected to fail to produce a functional MAC, as it lacks more than half of the normal protein. Thus, it was indicated that the nonsense mutation (c.1062C>G/p.Y354*) identified in the C6 gene may be a potential candidate factor for the development of C6D, which is consistent with previous findings (4,10). The terminal complement system is essential for fighting MD.…”

Section: Discussionsupporting

confidence: 91%

Identification of a novel mutation in the C6 gene of a Han Chinese C6SD child with meningococcal disease

et al. 2021

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Deficiency of the sixth complement component (C6D) is a genetic disease associated with increased susceptibility to Neisseria meningitides infection. Individuals with C6D usually present with recurrent meningococcal disease (MD). According to the patients' C6 levels, C6D is divided into complete genetic deficiency of C6 and subtotal deficiency of C6 (C6SD). The present study reported on a Han Chinese pediatric patient with MD, in whom further investigation revealed a C6SD genetic lesion. A heterozygote nonsense mutation (c.1062C>G/p.Y354*) in the C6 gene was identified by Sanger sequencing. The mutation alters the tyrosine codon at position 354 to a termination codon and results in a truncated protein. In conclusion, the genetic lesion of a pediatric patient with C6SD who was diagnosed due to having MD was investigated and a novel pathogenic mutation in the C6 gene was identified. The study confirmed the clinical diagnosis for this patient with C6SD and also expanded the spectrum of C6 mutations.

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Section: Discussionsupporting

confidence: 91%

Identification of a novel mutation in the C6 gene of a Han Chinese C6SD child with meningococcal disease

et al. 2021

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“…In the more common type 1 C2D, there is an absence of translated protein, usually caused by a 28 base pair deletion resulting in the generation of a premature termination codon; this allele is present in 1% of healthy western Europeans. 1 The rarer type 2 C2D is due to a failure in the secretion of the translated protein. 2 C2D is frequently asymptomatic, however, some patients suffer from infections with encapsulated bacteria and/or autoimmune diseases, particularly systemic lupus erythematosus.…”

Section: Discussionmentioning

confidence: 99%

Lessons of the month 2: Meningococcal epiglottitis and connective tissue disease associated with C2 deficiency

et al. 2021

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Case presentationA 68-year-old woman was referred for immunological investigation following an episode of meningococcal epiglottitis with associated septicaemia. Several years previously, she had been diagnosed with undifferentiated connective tissue disease. On investigation, alternative pathway complement function was normal; however, classical pathway complement activation was reduced. C1q, C3 and C4 levels were all measured and found to be within their respective normal ranges, but C2 levels were low. Sequencing of the C2 gene was subsequently performed, confirming a diagnosis of type 1 C2 deficiency (C2D). DiscussionC2D is usually hereditary and inherited in an autosomal recessive manner. C2D is often asymptomatic, however, some patients suffer from infections with encapsulated bacteria and/or autoimmune diseases, particularly systemic lupus erythematosus. Recognition of complement pathway deficiency is important due to the predisposition to severe and/or recurrent infections by encapsulated bacteria. Immunisations have the potential to reduce both mortality and morbidity not only for the patient but also for any affected relatives.

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“…Complement deficiencies can be either primary (hereditary) or acquired [for review, see ( 8 , 19 – 22 )]. The inheritance is usually autosomal recessive (exception: properdin deficiency: X-linked; Factor B, C1-INH, and MCP/CD46 deficiency: autosomal dominant).…”

Section: Clinical Relevance Of Complementmentioning

confidence: 99%

Expanding Horizons in Complement Analysis and Quality Control

Frazer‐Abel¹,

Kirschfink²,

Prohászka³

2021

Front. Immunol.

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Complement not only plays a key role in host microbial defense but also modulates the adaptive immune response through modification of T- and B-cell reactivity. Moreover, a normally functioning complement system participates in hematopoiesis, reproduction, lipid metabolism, and tissue regeneration. Because of its powerful inflammatory potential, multiple regulatory proteins are needed to prevent potential tissue damage. In clinical practice, dysregulation and overactivation of the complement system are major causes of a variety of inflammatory and autoimmune diseases ranging from nephropathies, age-related macular degeneration (AMD), and systemic lupus erythematosus (SLE) to graft rejection, sepsis, and multi-organ failure. The clinical importance is reflected by the recent development of multiple drugs targeting complement with a broad spectrum of indications. The recognition of the role of complement in diverse diseases and the advent of complement therapeutics has increased the number of laboratories and suppliers entering the field. This has highlighted the need for reliable complement testing. The relatively rapid expansion in complement testing has presented challenges for a previously niche field. This is exemplified by the issue of cross-reactivity of complement-directed antibodies and by the challenges of the poor stability of many of the complement analytes. The complex nature of complement testing and increasing clinical demand has been met in the last decade by efforts to improve the standardization among laboratories. Initiated by the IUIS/ICS Committee for the Standardization and Quality Assessment in Complement Measurements 14 rounds of external quality assessment since 2010 resulted in improvements in the consistency of testing across participating institutions, while extending the global reach of the efforts to more than 200 laboratories in 30 countries. Worldwide trends of assay availability, usage, and analytical performance are summarized based on the past years’ experiences. Progress in complement analysis has been facilitated by the quality assessment and standardization efforts that now allow complement testing to provide a comprehensive insight into deficiencies and the activation state of the system. This in turn enables clinicians to better define disease severity, evolution, and response to therapy.

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Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies

Cited by 43 publications

References 52 publications

Identification of a novel mutation in the C6 gene of a Han Chinese C6SD child with meningococcal disease

Identification of a novel mutation in the C6 gene of a Han Chinese C6SD child with meningococcal disease

Lessons of the month 2: Meningococcal epiglottitis and connective tissue disease associated with C2 deficiency

Expanding Horizons in Complement Analysis and Quality Control

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