Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Low C4A Gene Copy Number in Systemic Lupus Erythematosus.
Pereira4, Kaline M. C., Faria4, Atila G. A., Moreira1, Eloisa S., Santos3, Viviane C., Grecco3, Marcelle, Silva3, Neusa P., Andrade2, Luis Eduardo C.
Hospital Sirio Libanes, Brazil
Universidade Federal de São Paulo, Sao Paulo, Brazil
Universidade Federal de Sao Paulo - UNIFESP, Brazil
Universidade Federal de Sao Paulo - UNIFESP, Sao Paulo, SP, Brazil
C4 is an important component of Complement system and plays an essential role in the activation cascades of the classical Complement pathway. Complete deficiency of C4 is among the strongest genetic risk factors for systemic lupus erythematosus (SLE). There are two C4 circulating isoforms (C4A and C4B) encoded by C4A and C4B genes, respectively, that differ by only five nucleotides. C4A protein is involved in immune complex and apoptotic debris clearance while C4B protein is relevant in the defense against microbes. C4A and C4B genes are located at a gene cassette within the MHC class III region and depict gene copy-number variation (CNV). The number of C4A copies may be related to susceptibility to SLE.
To investigate the C4A and C4B gene CNV in patients with SLE.
One hundred SLE patients (meeting SLE ACR criteria) were sequentially retrieved from the rheumatology outpatient clinic and 100 healthy individuals (HI) without evidence of autoimmune diseases were retrieved among blood bank donors. Peripheral blood leukocyte DNA was amplified by quantitative real-time PCR (qPCR) technique using sequence specific TaqMan® probes with minor groove binding (MGB) non-fluorescent quencher. Gene copy number (GCN) was determined by the delta-delta cycle threshold (DDCT) method. Samples with known C4A and C4B GCN were kindly provided by Dr. Szilagyi (Hungary).
Gene copy number (GCN) varied from 2 to 8 for total C4 and from 0 to 5 for C4A and C4B. Patients with SLE had lower total C4 (C4A + C4B) and C4A GCN than HI. GCN for total C4 was lower in SLE patients (3.7 ± 1.2; 95% CI=3.5 3.9) in comparison with HI (4.3± 1.3; 95% CI= 4.0 4.5; p=0.003). This difference was due to C4A GCN variation that was lower in SLE (1.9 ± 1.0; 95% CI= 1.7 2.1) than in HI (2.3 ± 1.1; 95% CI=2.1 2.6; p=0.015). In contrast there was no difference in C4B GCN in both groups [(SLE = 1.8 ± 0.8; 95% CI= 1.6 1.9) and (HI = 1.9 ± 1.1; 95% CI=1.7 2.1) p=0.320]. The frequency of patients with only two C4 copies (C4A and/or C4B) was significantly higher in SLE (16%) than in HI (5%; p=0.028). The same was observed for subjects with only one C4A copy (SLE = 30%; controls = 16%; p=0.020). The frequency of patients with low C4 GCN (less than 4 copies) was significantly higher in SLE than in HI (40% versus 25%; p=0.022). The same was observed for low C4A gene dosage (less than 2 copies) (SLE = 35%; HI = 17%; p=0.009).
Patients with SLE presented lower C4A GCN as compared to control healthy individuals. This finding suggests that the ensuing relative deficiency in circulating C4A protein in individuals with low C4A GCN is one relevant risk factor for susceptibility to the development of systemic lupus erythematosus.
To cite this abstract, please use the following information:
Pereira, Kaline M. C., Faria, Atila G. A., Moreira, Eloisa S., Santos, Viviane C., Grecco, Marcelle, Silva, Neusa P., et al; Low C4A Gene Copy Number in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :498