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• W2331904553 abstract "<h3>Background</h3> The complement component C4 and its associated polymorphisms have a strong association with systemic lupus erythematosus (SLE). A low gene copy number (GCN) of C4 and its two isotypes (C4A and C4B) is a risk factor for SLE. At genetic level the C4 polymorphism has been studied in large groups of SLE patients of various ethnic origins. However, little is known about the relationship between these polymorphisms, serum protein levels, protein functional activity and clinical manifestations in SLE patients. <h3>Objectives</h3> The aim of this study was to assess C4 complement gene polymorphism, serum protein levels and protein functional activity in a cohort of SLE patients in relationship to clinical and serological manifestations. <h3>Methods</h3> Demographic data and ACR-criteria were collected in a cohort of 140 Dutch SLE patients (90% female, 69% Caucasian, mean age 42 yrs, mean disease duration 8.8 yrs). Measurements of total C4, C4A and C4B gene copy number, serum protein levels and protein functional activity were performed in SLE patients and in 104 healthy controls. Multiplex Ligation-dependent Probe Amplification (MLPA) assay, ELISA and functional C4 assay were used. [1,2] Statistical analyses were performed using Pearson’s chi square test, Mann-Whitney test and linear regression. <h3>Results</h3> A total C4 GCN of four was found in 35.7% of SLE patients, compared to 59.6% (p=0.0002) in controls. A GCN of less than four (i.e. a low GCN) was found in 55.7% (controls: 31.7%, p=0.0002); C4A and C4B deficiency (i.e. less than two copies) in 42.2% (controls: 25%, p=0.005) and 22.1% (controls: 33.6%, p=0.05) respectively. Median levels of serum protein and functional activity were significantly decreased in SLE patients versus controls, for both total C4 and the isotypes. As shown in table 1 presence of serositis was associated with lower C4A GCN as well as with lower C4A protein level and lower C4A functional activity. In addition associations were found between lower C4B protein level and lower C4B functional activity with presence of a history of nephritis, hemolytical anemia, anti-ds DNA and anticardiolipin antibodies. All these associations were also found in the Caucasian subgroup. <h3>Conclusions</h3> Complement C4 gene polymorphism, serum protein levels and for the first time also protein functional activity were studied in relationship to clinical and serological manifestations in SLE patients. The findings add to the understanding of the various phenotypes of systemic lupus erythematosus and advocate further studies in lupus nephritis patients. <h3>References</h3> Wouters D et al. Mol Immunol. 2009;46(4):592-600 Wouters D et al. Mol Immunol. 2007;44(16):3954 <h3>Disclosure of Interest</h3> None Declared" @default.
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• W2331904553 date "2013-06-01" @default.
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• W2331904553 title "THU0187 Complement C4 gene polymorphisms, serum protein levels and protein functional activity in relationship with clinical manifestations in patients with systemic lupus erythematosus:" @default.
• W2331904553 doi "https://doi.org/10.1136/annrheumdis-2012-eular.2152" @default.
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