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HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) region to the susceptibility to develop ACPA-positive RA in a Latin American (LA) population with admixed ancestry. A total of 289 ACPA-positive RA patients and 510 controls were enrolled in this study. The presence of HLA-DRB1*04:01, *09:01 and *10:01 was increased in ACPA-positive RA patients compared with healthy controls (p < 0.0001, p < 0.001 and p < 0.01, respectively), whereas DRB1*07:01 and *08:02 was associated with a decreased risk of ACPA-positive RA (p < 0.001 and p < 0.01, respectively). These results showed a strong correlation with estimates from studies in Asians but not in Caucasian populations. The present study describes the protective effects of the HLA-DRB1*07:01 and *08:02 alleles in ACPA-positive RA patients in a LA population for the first time. Identifying relationships between HLA-DRB1 alleles and RA is important for identifying disease associations in different ethnic groups in order to reach a better understanding of RA worldwide.

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It is known that polymorphisms of beta (2)-glycoprotein I (beta (2)GPI) in exon 7 affect interaction between the phospholipid binding site and the antibodies, and that other polymorphisms in exon 8 increase the generation of antibodies. In this study, we analyzed genetic polymorphisms of beta (2)GPI in unselected Chilean patients to determine the prevalence of beta (2)GPI polymorphisms in the phospholipid domain in patients with venous and arterial thrombosis and the clinical correlation with thromboembolic complications. This study comprised 149 patients with venous and arterial thrombosis (62 with venous thrombosis and 87 with arterial thrombosis) and 160 healthy controls with no previous history of thrombosis. Polymorphisms of exons 7 and 8 of beta (2)GPI, which encode for its fifth domain, were determined by PCR-RFLP. The presence of aPL or anti-beta (2)GPI in the patients was detected by ELISA. Anti-beta (2)GPI were present in 8/149 patients (5.4%); of these, five had aCL antibodies of low titer. The allele containing Val/Leu(247) and Trp/Ser(316) was significantly more frequent in patients with thrombosis than in the control group (OR=3.1, CI 1.6-6.0, p=0.0003; OR=2.9, CI 1.1-8.6, p=0.027, respectively). These polymorphisms did not correlate with aPL or anti-beta (2)GPI but significant differences were observed with venous thrombosis (p=<0.0001) and arterial thrombosis (p=0.026). In conclusion, the beta (2)GPI polymorphisms Val/Leu(247) and Trp/Ser(316) are not related to the presence of anti-beta (2)GPI antibodies in unselected Chilean patients with venous and arterial thrombosis, but they are significantly associated with venous and arterial thrombosis.

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Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-beta(2)GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further.

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BACKGROUND: Factor V Leiden and G20210A mutation of prothrombin gene are two important genetic polymorphisms associated with an increased risk for thrombosis. AIM: To establish the prevalence of factor V Leiden and prothrombin G20210A mutation in the Chilean population and their association to venous and arterial thromboembolism. MATERIAL AND METHODS: A case-control study was conducted where 149 patients with thrombosis (87 with arterial and 62 with venous thrombosis) confirmed by CAT-scan, electrocardiogram and cardiac enzymes or Doppler depending on the case, and 160 healthy blood donors were genetically analyzed for the presence of both polymorphisms. RESULTS: Factor V Leiden mutation was found in 5.4% of patients and in 1.3% of healthy controls (p=0.04). Heterozygosity for G20210A prothrombin mutation was found in 5.4% of patients and in 2.5% of the control group (p=NS). When arterial and venous thrombosis were considered as separate entities, 4.6% of patients with arterial thrombosis and 6.5% with venous thrombosis presented factor V Leiden (p=NS). Likewise, 8.1% of patients with venous thrombosis and 3.5% of patients with arterial thrombosis had G20210A prothrombin mutation (p=NS). CONCLUSIONS: In non selected consecutive Chilean patients with arterial and venous thrombosis the frequency of factor V Leiden and prothrombin G20210A is less than we could expect from their prevalence in the general population.

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Antiphospholipid antibodies (aPL) are a heterogeneous family of antibodies associated with thrombotic events and other complications. The objective of this study was to investigate the prevalence of aPL in a group of Chilean patients with thrombosis. Two hundred and twenty-six patients with venous and arterial thrombosis and 95 healthy controls were studied. Anticardiolipin (aCL), anti-beta(2 )glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies were determined. Eighty-eight out of 226 (38.9%) patients with thrombosis had some type of aPL. Fifty-seven patients (25.2%) were positive for aCL, 31 (13.7%) for aPT, and 14 (6.2%) for anti-beta(2)GPI antibodies. Twelve patients (5.3%) were positive for more than one aPL. IgG, IgM and IgA isotypes were observed in aCL, anti-beta(2)GPI, and aPT antibodies. Twenty-six out of 92 (28.3%) patients with venous thrombosis and 31/134 (23.1%) patients with arterial thrombosis were positive for aCL antibodies. With regard to the control group (4/95=4.2%), the odd ratios (OR) were 5.2 (1.3-19.8; p0.01) and 5.7 (1.6-22.3; p0.01), respectively. Additionally, we observed statistically significant OR with aPT and anti-beta(2)GPI antibodies; in the first, with venous and arterial thrombosis, and in the second, only with arterial thrombosis. Our results show a significant prevalence of aPL, predominantly aCL and aPT antibodies, in patients with thrombosis. Additionally, aCL and aPT antibodies appear to be a risk factor for venous and arterial thrombosis, and anti-beta(2)GPI antibodies appear to be a risk factor for arterial thrombosis.

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Antiphospholipid antibodies (aPLs) are a heterogeneous family of antibodies found in autoimmune disorders, infectious diseases, and other situations. The presence of different aPLs has been associated with various clinical manifestations of the antiphospholipid syndrome (APS). The objective of this study was to investigate the prevalence of aPLs in a group of 90 Chilean patients with systemic lupus erytematosus (SLE) and 90 healthy controls. We measured anticardiolipin antibodies (aCLs), antiphosphatidylserine antibodies (aPSs), anti-beta(2) glycoprotein I antibodies (anti-beta(2)GPIs), and antiprothrombin antibodies (aPTs) with an enzyme-linked immunosorbent technique using "in-house" assays. Fifty-four of 90 SLE patients (60.0%) had some type of aPL. Forty of 90 (44.4%) were positive for aCLs, 9 of 61 (14.8%) had aPSs, 21 of 90 (23.3%) had anti-beta(2)GPIs, and 18 of 90 (20.0%) had aPTs. In the control group, prevalences were as follows: aCLs, 3.3%; aPSs, 1.1%; anti-beta(2)GPIs, 1.1%; aPTs, 2.2%. In most cases, values were in the low-positive range. Of all aPL detected, 29.5% was of the IgG isotype, 37.5% IgM, and 33.0% IgA. We observed a correlation between aCLs and aPSs and of these antibodies with anti-beta(2)GPIs and aPTs but not between anti-beta(2)GPIs and aPTs. Our results show a high prevalence of aPLs in SLE patients. An association between different specificities and isotypes of aPLs was also observed.

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