PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis.

Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
Arthritis & Rheumatology (Impact Factor: 7.48). 11/2007; 56(10):3502-8. DOI: 10.1002/art.22922
Source: PubMed

ABSTRACT To investigate potential associations of the PlA1/A2 polymorphism of the platelet glycoprotein IIIa (GPIIIa) gene with susceptibility to, and clinical expression of, giant cell arteritis (GCA).
One hundred forty patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 241 population-based healthy controls from the same geographic area were genotyped for the PlA1/A2 polymorphism of the platelet GPIIIa gene by molecular methods. The patients were divided into subgroups according to the presence or absence of polymyalgia rheumatica and cranial ischemic complications. The distribution of the PlA1/A2 genotype was investigated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
The distribution of the PlA1/A2 genotype differed significantly between GCA patients with and those without visual loss caused by anterior ischemic optic neuritis (P = 0.016, corrected P [P(corr)] = 0.048). The PlA2 allele was found significantly more frequently in GCA patients with anterior ischemic optic neuritis than in those without anterior ischemic optic neuritis (P = 0.023, P(corr) = 0.046, OR 2.4 [95% CI 1.2-4.8]). Homozygosity for the PlA2 allele was significantly more frequent among GCA patients with anterior ischemic optic neuritis than among those without (P = 0.019, P(corr) = 0.038, OR 7.1 [95% CI 1.64-30.6]). Cranial ischemic complications occurred in 8 of 19 patients (42.1%) receiving antiplatelet therapy, compared with 22 of 118 patients (18.6%) not receiving such therapy (P = 0.03, OR 3.2 [95% CI 1.1-8.8]).
Our findings show that A2/A2 homozygosity is associated with an increased risk of visual loss due to anterior ischemic optic neuritis in GCA patients. Antiplatelet therapy, however, was not effective in reducing the risk of ischemic events in this population of GCA patients.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ischemia is a leading causes of morbidity in giant cell arteritis (GCA). We studied circulating platelets and leukocytes in patients with GCA and with polymyalgia rheumatica. Normal healthy donors (>60 a) served as controls. Patients had a significantly greater fraction of platelets expressing P-selectin, of platelet-Nph and platelet-Mo aggregates, and of Nph and Mo expressing tissue factor. These differences were correlated with the percentage of platelets expressing P-selectin and were not influenced by clinical features or by systemic inflammation. Activated circulating leukocytes and platelets could contribute to indolent vessel inflammation and possibly to thromboembolic events in patients with systemic large vessel vasculitis.
    Autoimmunity 05/2009; 42(4):386-8. · 2.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory diseases that typically affect white individuals >50 years. Women are affected ∼2-3 times more often than men. PMR and GCA occur together more frequently than expected by chance. The main symptoms of PMR are pain and stiffness in the shoulders, and often in the neck and pelvic girdle. Imaging studies reveal inflammation of joints and bursae of the affected areas. GCA is a large-vessel and medium-vessel arteritis predominantly involving the branches of the aortic arch. The typical clinical manifestations of GCA are new headache, jaw claudication and visual loss. PMR and GCA usually remit within 6 months to 2 years from disease onset. Some patients, however, have a relapsing course and might require long-standing treatment. Diagnosis of PMR and GCA is based on clinical features and elevated levels of inflammatory markers. Temporal artery biopsy remains the gold standard to support the diagnosis of GCA; imaging studies are useful to delineate large-vessel involvement in GCA. Glucocorticoids remain the cornerstone of treatment of both PMR and GCA, but patients with GCA require higher doses. Synthetic immunosuppressive drugs also have a role in disease management, whereas the role of biologic agents is currently unclear.
    Nature Reviews Rheumatology 07/2012; 8(9):509-21. · 9.75 Impact Factor
  • Current Immunology Reviews 11/2011; 7(4):435.

Full-text (2 Sources)

Available from
May 29, 2014