Journal article
The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes
The Journal of immunology (1950), v 169(3), pp 1570-1578
01 Aug 2002
PMID: 12133986
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Abstract
The disease course of a complete C4-deficient patient in the U.S. was followed for 18 years. The patient experienced multiple episodes of infection, and he was diagnosed with systemic lupus erythematosus at age 9 years. The disease progressed to WHO class III mild lupus nephritis and to fatal CNS vasculitis at age 23 years. Immunochemical experiments showed that the patient and his sibling had complete absence of C4A and C4B proteins and were negative for the Rodgers and Chido blood group Ags. Segregation and definitive RFLP analyses demonstrated that the patient and his sibling inherited two identical haplotypes, HLA A2 B12 DR6, each of which carries a defective long C4A gene and a defective short C4B gene. PCR and DNA sequencing revealed that the mutant C4A contained a 2-bp insertion in exon 29 at the sequence for codon 1213. The identical mutation was absent in the mutant C4B. The C4B mutant gene was selectively amplified by long range PCR, and its 41 exons were completely sequenced. The C4B mutant had a novel single C nucleotide deletion at the sequence for codon 522 in exon 13, leading to frame-shift mutation and premature termination. Thus, a multiplex PCR is designed by which known mutations in C4A and C4B can be elucidated conveniently. Among the 28 individuals reported with complete C4 deficiency, 75-96% of the subjects (dependent on the inclusion criteria) were afflicted with autoimmune or immune complex disorders. Hence, complete C4 deficiency is one of the most penetrant genetic risk factors for human systemic lupus erythematosus.
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Details
- Title
- The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes
- Creators
- Kristi L Rupert - The Ohio State UniversityJoann M Moulds - ∥Department of Microbiology and Immunology, MCP Hahnemann University School of Medicine, Philadelphia, PA 19129;Yan Yang - *Children’s Research Institute, Departments ofFrank C Arnett - The University of Texas Health Science Center at HoustonRobert W Warren - Texas Children's HospitalJohn D Reveille - The University of Texas Health Science Center at HoustonBarry L Myones - Baylor College of MedicineCarol A Blanchong - *Children’s Research Institute, Departments ofC Yung Yu - *Children’s Research Institute, Departments ofYonghong F Yang - Psychiatry
- Publication Details
- The Journal of immunology (1950), v 169(3), pp 1570-1578
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Psychiatry
- Web of Science ID
- WOS:000177025100054
- Scopus ID
- 2-s2.0-0036681601
- Other Identifier
- 991019167528904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology