ABSTRACT
Severe aplastic anemia (SAA) is a heterogeneous hematological disorder with a high mortality. Genetic predisposition has been shown to play a role in a considerable proportion of SAA cases. For instance, the human lymphocyte antigen HLA-DR2 has been repeatedly demonstrated to be over-represented in SAA patients. In this paper, we expand on the evidence for the contribution of HLA polymorphism in the susceptibility to SAA, which was obtained using the "high-resolution" technique of HLA-DRB1 subtyping. The DRB1*1501 allele appeared to be responsible for the predominance of DR2 specificity in SAA patients and was the most significant risk factor for this disease. It was observed in 23/44 (52.3%) patients versus 22/100 (22.0%) donors [odds ratio (OR) = 3.9; 95% confidence interval (CI): 1.8-8.3; P = 0.0005, corrected P (Pc) < 0.05]. In addition, DRB1*04 alleles also displayed non-random distribution in the SAA group. In particular, DRB1*04 variants coding for alanine at position 74 of the DR beta 1 chain (HLA-DR4-Ala74 beta subtype) were detected in all 13 DR4-positive SAA patients but only in 15/24 (62.5%) controls (OR = 16.6; 95% CI: 0.9-312.0; P = 0.015). Multiple comparison analysis confirmed that the HLA-DR4-Ala74 beta subtype confers susceptibility to SAA independently from the DRB1*1501 allele. Finally, examination of the clinical records has shown that the HLA-DR4-Ala74 beta subtype is associated with poor outcome of SAA.
Subject(s)
Anemia, Aplastic/immunology , Adolescent , Adult , Anemia, Aplastic/epidemiology , Child , Child, Preschool , Disease Susceptibility/immunology , Female , Genotype , HLA-DR Antigens/genetics , HLA-DR4 Antigen/genetics , HLA-DRB1 Chains , Humans , Male , Middle Aged , Odds Ratio , Outcome Assessment, Health Care , Risk FactorsABSTRACT
Prevalence of human papillomavirus (HPV) infection was estimated in women from St. Petersburg, Russia. The study included 309 attendants of gynecological practice, who met the following criteria: (1) history of sexual activity; (2) reproductive age; (3) lack of evidence for a specific disease of the genital tract or a current pregnancy; and (4) no cervical abnormalities revealed by cytological examination. Papillomavirus detection was carried out by PCR using MY09/11 primers. Ninety (29%) females turned out to be HPV-positive. HPV presence did not correlate with the current age, age at the sexual debut, or time interval since the first intercourse. However, women with the history of more than two contraceptive abortions had a higher prevalence of papillomavirus infection as compared to the remaining group (30/66 (45%) vs. 56/207 (27%); P = 0.005; OR = 2.25 (1.27-3.97)). HPV genotyping procedure involved reverse dot-blot hybridization and restriction endonuclease analysis. High-risk, low-risk and non-identified viruses were detected in 58, 26, and 16% of the positive samples, respectively. HPV16 was the most prevalent type, being present alone in 21% of the infected women, and in combination with other HPVs in 5% of the virus-positive females. No other papillomavirus types showed exceptionally prominent prevalence. The data suggest that HPV occurrence among Russian women is within the range of world-wide variations.
