HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma).

Abstract

Objective-To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). Methods-HLA class II genes were determined using polymerase chain reaction/ restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. Results-Frequency of DQBI*0501 was increased in ACA positive SSc patients compared with ACA negative SSc patients (36% versus 13%; p = 0-02, odds ratio = 4 0, 95% confidence interval 1 1 to 13.9), but the association ofACA with a polar amino acid at position 26 in the DQB1

Anti-centromere Antibody-positive Subjects Presenting with Hypertensive Emergency and Renal Dysfunction in the Absence of Skin Manifestations: A Variant of Systemic Sclerosis or a Novel Entity?

“…Previous studies investigated the association of HLA genotyping with disease susceptibility in ACApositive patients. A high frequency of the HLA-DQB1*0501 or DRB1*0101 alleles in Japanese patients with ACApositive SSc was reported (12,13), whereas none of the patients in the present study had them. Furthermore, though HLA-DRB1*0803 is reportedly associated with the development of PBC in Japanese (14), the gene was present in only 1 patient (Patient 5) who was asymptomatic but had positive anti-mitochondrial antibodies.…”

Is systemic sclerosis an antigen‐driven T cell disease?

“…Anti-topo I antibodies are characteristic of the diffuse type of SSc (1,120). The possibility that an autoantigen elicits both an autoantibody response and a cellular response is supported by the findings of a substantially stronger HLA association with autoantibody profiles than with the disease itself (64)(65)(66)(67)(68)140). Kuwana et al reported that HLA-DQ and DR genes together control the anti-topo I antibody response in patients with SSc (68).…”

“…Antibodies to CENP-E, a centromere kinesin-like protein, are found mostly in a rather infrequent form of SSc known as the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), and their presence is associated with the HLA-DQB1*05 alleles (121). Certain HLA-DRB1 (DRB1*0101,*0405, and *01302) or DQB1 (DQB1*0501) alleles were found to be associated with high serum anticentromere titers (140).…”

Unraveling the genetic component of systemic sclerosis

“…Hence, most of the strongest associations are found within the major autoantibody positive subgroup of patients ( Table 2). 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).…”