Deficiency of C4a Is a Genetic Determinant of Systemic Lupus Erythematosus in Three Ethnic Groups

Dunckley, H.; Gatenby, Paul A.; Hawkins, B. R.; Naito, Setsuya; Serjeantson, S. W.

doi:10.1111/j.1744-313x.1987.tb00383.x

Cited by 98 publications

(31 citation statements)

References 14 publications

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“…[28][29][30][31][32][33][34] C4A*Q0 is also associated with SLE susceptibility in multiethnic Asian populations, including Japanese and Chinese. 35 This result has been replicated in Korean, 19 Japanese 36 and Chinese, 37 but also not in Chinese 16 and Malaysian. 38 However, C4A*Q0 is known to be in linkage disequilibrium with HLA-DR3.…”

Section: Resultsmentioning

confidence: 93%

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Kim

et al. 2009

Genes Immun

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There have been many genetic studies of systemic lupus erythematosus (SLE) in Asia, but the status of SLE in Asia remains unclear. Genes that have been associated with SLE in Caucasians have shown both consistent and inconsistent results in Asians. This prompted us to review studies of SLE-associated genes and compare the degree of consistency according to ethnicity in Asia. We searched PubMed and the national databases in Korea and Japan for SLE genetic studies. A total of 755 articles were found and after applying various exclusion criteria, 442 studies including 17 linkage studies, 2 genome-wide association studies and 423 candidate-gene analyses were reviewed. Nine linkage loci were confirmed to be associated with SLE susceptibility in non-Asians, but the risk locus (16q12) has been identified in only one Asian study. A total of 156 candidate genes were analyzed, of which 92 were studied in Asians. Although there were allelic (HLA-DRB1 and IRF5) or genetic heterogeneity (FCGR gene family), HLA-DRB1, the FCGR gene family, IRF5, STAT4 and MECP2 showed consistent associations with SLE susceptibility across ethnicities. In conclusion, genetic associations often vary with ethnicity, requiring validation in different ethnic groups, and hence future SLE genetic studies will require strong worldwide collaborations.

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Section: Resultsmentioning

confidence: 93%

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Kim

et al. 2009

Genes Immun

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“…However, it should be noted that 2 erythrocyte blood group antigens, Rodgers and Chido, have been shown to correspond to the C4d region of C4A and C4B, respectively (16,28), suggesting that both C4A and C4B can bind to and persist on the surface membranes of normal erythrocytes. C4-null alleles or partial deficiency of C4A and/or C4B has been associated with human SLE (36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

Liu

Manzi

Kao

et al. 2005

Arthritis & Rheumatism

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Objective. There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activationderived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest-lived erythrocytes (lifespan 24-48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE.Methods. We conducted a cross-sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2-color flow cytometric assay. The results were analyzed for correlations with SLE disease activity.Results. A wide range of increased levels of reticu-

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“…The relative importance of disease-related polymorphic genes, such as MHC class II, C4A, IgG heavy chain variable region, may also vary among groups (26,(38)(39)(40)(41)(42)(43)(44). Among Hispanics in Venezuela, a study of 41 patients also suggested an increased frequency of a phenotype containing at least one Fc␥RIIA-R131 gene (45).…”

Section: Discussionmentioning

confidence: 99%

Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans.

Salmon¹,

Millard²,

Schachter³

et al. 1996

J. Clin. Invest.

457

289

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Allelic variants of Fc ␥ R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc ␥ RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc ␥ RIIa-H131 is the only human Fc ␥ R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc ␥ RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc ␥ RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc ␥ RIIA alleles, with only 9% of SLE patients homozygous for Fc ␥ RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P ϭ 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc ␥ RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc ␥ RIIA-H131 as the likelihood for lupus nephritis increased ( P ϭ 0.0004) consistent with a protective effect of the Fc ␥ RIIA-H131 gene. The skewing in the distribution of Fc ␥ RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans. ( J.

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Deficiency of C4a Is a Genetic Determinant of Systemic Lupus Erythematosus in Three Ethnic Groups

Cited by 98 publications

References 14 publications

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans.

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