Anti-centromere antibodies (ACA) in systemic sclerosis patients and their relatives: a serological and HLA study

McHugh, Neil; Whyte, Jean; Artlett, Carol M.; Briggs, David; Stephens, Clare; Olsen, Nancy J.; Gusseva, N G; Maddison, Peter J.; Black, Carol M.; Ki, Welsh

doi:10.1111/j.1365-2249.1994.tb06552.x

Cited by 41 publications

(15 citation statements)

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“…The most solid, replicated associations with the autoantibody subgroups are the HLA-DQB1*0501/HLA-DRB1*0101 haplotype with the production of ACA (Arnett et al 2010;Simeon et al 2009;Kuwana et al 1999;Kuwana et al 1995), HLA-DRB1*1104 and HLA-DPB1*1301 with the production of ATA (Simeon et al 2009;Gilchrist et al 2001;Fanning et al 1998) and HLA-DQB1*0302 with the production of ARA (Arnett et al 2010;Kuwana et al 1999). It is noteworthy that the Wrm association of the absence of a polar aminoacid in the position 26 of the HLA-DQB1 molecule with the presence of ACA which has been only found in populations of Caucasian origin (Arnett et al 2010;Gilchrist et al 2001;McHugh et al 1994;Beretta et al 2011).…”

Section: Hla Genesmentioning

confidence: 99%

Unraveling the genetic component of systemic sclerosis

2012

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Systemic sclerosis (SSc) is a severe connective tissue disorder characterized by extensive fibrosis, vascular damage, and autoimmune events. During the last years, the number of genetic markers convincingly associated with SSc has exponentially increased. In this report, we aim to offer an updated review of the classical and novel genetic associations with SSc, analyzing the firmest and replicated signals within HLA and non-HLA genes, identified by both candidate gene and genome-wide association (GWA) studies. We will also provide an insight into the future perspectives and approaches that might shed more light into the complex genetic background underlying SSc. In spite of the remarkable advance in the field of SSc genetics during the last decade, the use of the new genetic technologies such as next generation sequencing (NGS), as well as the deep phenotyping of the study cohorts, to fully characterize the genetic component of this disease is imperative.

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Section: Hla Genesmentioning

confidence: 99%

Unraveling the genetic component of systemic sclerosis

2012

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“…[3] The presence of multiple SSc-associated autoantibodies, most commonly anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA), has been well described in SSc patients and provides indirect evidence for the importance of the B-cell lineage in SSc. [4–6] Interestingly, the SSc-associated autoantibodies correlate with distinct clinical subsets characterized by extent of cutaneous involvement and pattern of organ involvement. [7;8] For example, pulmonary arterial hypertension is more common in patients with anti-centromere antibodies (ACA), pulmonary fibrosis is more common in patients with anti-topoisomerase antibodies (ATA), and scleroderma renal crisis is more common in patients with anti-RNA polymerase III antibodies (ARA).…”

Section: Introductionmentioning

confidence: 99%

Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations

Gourh

Agarwal

Martín

et al. 2010

Journal of Autoimmunity

121

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Objective Genetic studies in the systemic sclerosis (SSc), an autoimmune disease that clinically manifests with dermal and internal organ fibrosis and small vessel vasculopathy, have identified multiple susceptibility genes including HLA-class II, PTPN22, IRF5, and STAT4 which have also been associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE). These data suggest that there are common autoimmune disease susceptibility genes. The current report sought to determine if polymorphisms in the C8orf13-BLK region (chromosome 8p23.1-B lymphoid tyrosine kinase), which is associated with SLE, are associated also with SSc. Methods Two variants in the C8orf13-BLK region (rs13277113 & rs2736340) were tested for association with 1050 SSc cases and 694 controls of North Americans of European descent and replicated in a second series 589 SSc cases and 722 controls from Spain. Results The “T” allele at rs2736340 variant was associated with SSc in both the U.S. and Spanish case-control series (P=6.8×10−5, OR 1.27, 95%CI 1.1–1.4). The “A” allele at rs13277113 variant was associated with SSc in the U.S. series only (P=3.6×10−4, OR 1.32, 95%CI 1.1–1.6) and was significant in the combined analyses of the two series (P=2.0×10−3; OR 1.20, 95%CI 1.1–1.3). Both variants demonstrated an association with the anti-centromere antibody (P=2.2×10−6 and P=5.5×10−4, respectively) and limited SSc (P=3.3×10−5 and P=2.9×10−3, respectively) in the combined analysis. Peripheral blood gene expression profiles suggest that B-cell receptor and NFκB signaling are dysregulated based on the risk haplotype of these variants. Conclusion We identify and replicate the association of the C8orf13-BLK region as a novel susceptibility factor for SSc, placing it in the category of common autoimmune disease susceptibility genes.

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“…Autoantibodies to centromeric proteins are found in 22%-55% of patients with lSSc and are strongly associated with the specific disease variant [61], although various reports have described the presence of ACA in large series of unselected patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjö gren Syndrome (SSj) [62,63]. IIF has historically been used as a routine screening test for ACA detection and remains the gold standard.…”

Section: Discussionmentioning

confidence: 99%