Protective effect of CCR5-Δ32 against HIV infection by the heterosexual mode of transmission in a Polish population.

Effects of chemokine receptor alleles (CCR5-Δ32 and CCR2-64I) on susceptibility to human immunodeficiency virus (HIV) infection were studied in a Polish population. The CCR5 and CCR2 genotypes were determined for 311 healthy, HIV-negative individuals (control group), 121 exposed to HIV infection but uninfected (EU group), and 470 HIV-positive patients. The frequency of the alleles in the control group was calculated as 0.12 for both CCR5-Δ32 and CCR2-64I. The logistic regression method was used to analyze the effects of the described factors. A protective effect was observed for the CCR5-Δ32 allele but only in the case of heterosexual exposure. Prevalence of the CCR5-Δ32/+ genotype in HIV(+) patients infected via the heterosexual route (n=61; 8.2%) was much lower than in the control group (n=311; 21.5%); in the heterosexually exposed uninfected group it was slightly higher (n=28; 25%). This suggested that in this mode of infection, the native CCR5 expression level was crucial for establishment of infection. Individuals with the CCR5-Δ32 allele have more than three times less chance of infection in the case of HIV heterosexual exposure (odds ratio, 3.37; 95% confidence interval, 1.055-10.76). However, a protective effect of the CCR5-Δ32/+ genotype was not observed in the case of intravenous drug users (IDUs). The rates of the genotype were similar in HIV-infected IDU individuals (n=356; 17.7%) and in exposed uninfected patients (n=84; 15.5%), not significantly different from control group. No effect of the CCR2 genotype was observed. The analysis revealed that the important factor increasing infection risk was, in particular, hepatitis C virus (HCV) infection (odds ratio, 12.9). Moreover, the effect of HCV infection was found to be age dependent. Susceptibility to HIV infection resulting from HCV positivity became weaker (6% per year) with increasing age.

Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.

We analyzed the incidence, etiology, risk factors, and clinical management of hemorrhagic cystitis (HC) in 102 children who underwent allogeneic stem cell transplantation: 28 from matched siblings, 57 from unrelated donors, and 17 from mismatched relatives. Conditioning regimens consisted of high-dose chemotherapy (n=83) or total body irradiation (n=19). In all children, urine and plasma were prospectively screened for human polyomavirus (HPV; BK virus [BKV] and JC virus [JCV]) or adenovirus (AdV) DNA with a polymerase chain reaction-based assay. Viral DNA was detected in the urine of 56 children (54.9%): BKV in 48 (47%), JCV in 4 (3.9%), and AdV in 4 (3.9%). HC occurred in 26 children (25.5%), and viruria was detected in all of them: BKV in 21 (80.8%), AdV in 4 (14.4%), and JCV in 1 (3.8%). All patients with AdV viruria developed HC. The cumulative incidence of HC in patients with HPV viruria was 0.43. The only significant risk factor for HC in patients with HPV-positive urine was conditioning with high-dose chemotherapy. Twenty-two children were treated with cidofovir, with no significant toxicity. In all treated patients but 1, the clinical symptoms were moderate, and no HC-related death was observed. We conclude that virus-induced HC is a frequent complication after allogeneic hematopoietic cell transplantation. Treatment with cidofovir is feasible, and further studies are warranted to evaluate its activity in HC mediated by BKV or JCV.

Age related natural antiviral non-specific immunity of human leukocytes.

BACKGROUND: The purpose of our study was to examine the dependence of innate antiviral immunity on age and sex in human leukocytes. MATERIAL/METHODS: Innate antiviral immunity was measured by using the direct method of infection of leukocytes with vesicular stomatitis virus (VSV), which was selected as the indicatory virus for detection of immunity. The lack of VSV replication by infected leukocytes (0-1 log TCID50) was taken as an indicator for complete immunity; a low level of VSV replication (2-3 log) for partial immunity; and a high VSV titer (4 or more log) for the no or very low immunity. RESULTS: The kinetics of VSV replication was studied in leukocytes isolated from 127 individuals ranging in a age from 0 to 89 years. Individual differentiation in the kinetics of VSV replication indicated differing degrees of innate immunity even in newborns. Age-related differences in natural immunity were observed: low immunity in newborns, highest in the age group 31-40, and reduced in the age group >60. Sex dependent innate immunity was shown in the group of aged persons, as innate immunity was higher in women than in men. CONCLUSIONS: Innate immunity of leukocytes develops to age 30-40, after which immunity is gradually reduced. Sex dependence was observed only in the group of elderly persons, where women expressed higher immunity; this is probably a reason for their statistically greater longevity.

[Virus infection in children after allogenic stem cell transplantation ]. / Zakazenia wirusowe u dzieci po allogenicznym przeszczepieniu komórek krwiotwórczych.

Allogenic hematopoietic cell transplantation (alloHCT) is the treatment of choice for various pediatric malignancies and nonmalignant diseases. The most prominent complication of allotransplantation is graft vs host disease (GvHD). The treatment of GvHD influence negatively function of immune system and increase risk of bacterial, fungal and viral infections. Clinical symptoms of viral infection may mimic GvHD and lead to inappropriate treatment. Human cytomegalovirus (CMV, Herpesviridae) has been recognized as most important viral pathogen after alloHCT. Increasing number of procedures, especially from alternative donors, requiring more intensive immunosuppression, led to identification more viral pathogens causing transplant related mortality and morbidity. Among them are adenoviruses (ADV, Adenoviridae), BK and JC viruses (Papovaviridae) and human herpes virus 6 (HHV-6, Herpesviridae). Frequency of complications caused by those pathogens is higher in children then in adults.

[Emphysema connected with Alpha-1 anti-trypsin deficiency]. / Rozedma pluc zwiazana z niedoborem alfa 1 antytrypsyny.

45-years old smoker with 6 years history of COPD symptoms has been described. Taking into consideration rapid deterioration of lung functions leading to respiratory insufficiency as well as young age of patient at the onset of the diseases, alfa 1 anti-trypsin (AAT) level was estimated in serum. Significantly decreased AAT level led to AAT deficiency syndrome diagnosis and to introduction of substitutory treatment.