Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus

Kyushu University, Hukuoka, Fukuoka, Japan
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 04/2005; 330(1):298-304. DOI: 10.1016/j.bbrc.2005.02.159
Source: PubMed


A case of inherited homozygous complement C3 deficiency (C3D) in a patient with systemic lupus erythematosus (SLE) and the molecular basis for this deficiency are reported. A 22-year-old Japanese male was diagnosed as having SLE and his medical history revealed recurrent tonsillitis and pneumonia. He was diagnosed as having C3D because of undetectable serum C3 level. His parents were consanguineous. Sequence analysis of C3D cDNA revealed a homozygous deletion of exon 39 (84bp). A single base substitution (AG to GG) in the 3'-splice acceptor site of intron 38 was identified by sequencing the genomic DNA. Expression of C3Delta(ex39) cDNA, the C3cDNA lacking exon 39, in COS-7 cells revealed that C3Delta(ex39) was retained in endoplasmic reticulum-Golgi intermediate compartment because of defective secretion. These data indicate that a novel AG-->GG 3'-splice acceptor site mutation in intron 38 caused aberrant splicing of exon 39, resulting in defective secretion of C3.

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Available from: Takahiko Horiuchi, Oct 20, 2014
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    • "Systemic lupus erythematosus (SLE or Lupus) is an autoimmune disease that can attack the body's normal tissue and cells, resulting in inflammation and tissue damage [1, 2]. SLE occurs at any age and in any gender. "
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    ABSTRACT: Systemic lupus erythematosus (SLE) develops in relation to many environmental factors. In our opinion, it is more important to investigate the effect of melatonin on the environmental- related SLE. In the present study, 0.5 ml pristane were used to induce SLE in female BALB/c mice. Melatonin (0.01, 0.1, 1.0 mg/kg) was orally administered immediately after pristane-injection for 24 weeks. IgM anti ssDNA and histone antibodies were detected after 0, 1, 2, 4, 8 weeks pristane injection. The levels of IL-2, IL-6 and IL-13 were detected after 24 weeks. Renal lesions were also observed. The results showed that melatonin antagonized the increasing levels of IgM anti ssDNA and histone autoantibodies. Melatonin could also decrease the IL-6 and IL-13 production and increase the IL-2 production. Besides, melatonin could lessen the renal lesions caused by pristane. These results suggested that melatonin has a beneficial effect on pristane-induced lupus through regulating the cytokines disturbances.
    Mediators of Inflammation 07/2010; 2010(0962-9351). DOI:10.1155/2010/951210 · 3.24 Impact Factor
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    • "The deficiency is caused by mutations in the C3 gene, resulting in absence/markedly reduced levels, or dysfunction of the protein [4]. The disorder is rare, only 23 families (31 individuals) have been identified to date [for review see 3], [5]–[7] and ten different, unique mutations have been found in the C3 encoding gene [8]–[15]. In most cases, the defect is found in consanguineous family and noted already in infancy or early childhood due to life-threatening infections during the first year of life. "
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    ABSTRACT: Dried 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. We 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. The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.
    PLoS ONE 02/2009; 4(4):e5321. DOI:10.1371/journal.pone.0005321 · 3.23 Impact Factor
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