Evidence for an HLA‐Linked Resistance Gene in Buerger's Disease

Abstract

The incidence of Thromboangiitis Obliterans in brothers and the high prevalence in some ethnic groups have led us to investigate the histocompatibility HLA—A, B and DR antigens of 46 Buerger's disease patients. The main result indicates a marked decreased frequency of the B12 antigen: 2.2% vs 28% in controls. Our study suggests that Buerger's disease is, on the basis of HLA antigens, a distinct immunogenetic entity and not a particular form of arteriosclerosis. Moreover, this disorder may represent a clue to the existence of resistance genes linked to HLA.

Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients

“…Patients with Buerger's disease present a statistically significantly higher frequency of HLA‐DR4 and a significantly lower frequency of the HLA‐DRW6 antigen. This observation may serve as further evidence that an autoimmune mechanism is involved in TAO [22,24]. Our study complements these findings, further emphasizing the participation of autoimmune mechanisms in the aetiology of the development of TAO, as we show significant increases of IL‐17 and IL‐23, cytokines related closely to autoimmunity activation [25–27].…”

“…By using an antigen-sensitive thymidine-incorporation assay, Adar et al [21] showed that patients with TAO have an increased cellular sensitivity to types I and III collagen compared to patients with arteriosclerosis obliterans or healthy males. De Moerloose et al [22] found a marked decrease in the Similarly to other autoimmune diseases, TAO may have a genetic predisposition without a direct 'causative' gene mutation. Most investigators believe that TAO is an immunemediated endarteritis.…”

“…De Moerloose et al . [22] found a marked decrease in the frequency of human leucocyte antigen (HLA)‐B12 in patients with Buerger's disease (2·2% versus 28% in controls).…”

One of the most frequent vascular diseases in northeastern of Turkey: Thromboangiitis obliterans or Buerger's disease (experience with 344 cases)

“…A significant increase in several human leukocyte antigen (HLA) subtypes has been reported in patients with Buerger's disease by several investigators: A9, B5, A1, B8 and DR4 [19,20]. It has also been suggested that HLA-B12 antigen may be associated with disease resistance, since it is almost never detected in patients with Buerger's disease [21]. Eichhorn et al [22] identified significantly elevated antiendothelial cell antibodies in a small group of patients with active Buerger's disease [23].…”

Guideline for Management of Vasculitis Syndrome (JCS 2008) - Digest Version -

“…70-72 There is a negative association between this disease and HLA-B12. 73 The incidence of Buerger disease is low among individuals with HLA-DPB1*0401 and those with HLA-DRB*1302. 74 …”