Anti-human leukocyte antigen antibodies are present in blood of blood donors: is therapy with blood preparations safe for graft recipients?

BACKGROUND: Blood products infusions are often administrated to graft recipients. Post-transfusion reactions of anti-human leukocyte antigen antibodies (anti-HLA) are responsible for transfusion-related acute lung injury, but cases of graft rejection after blood product infusions were recently also proven. METHODS: The aim of this study was to assess, with the use of the very sensitive Luminex technology and traditional lymphocytotoxic test, the prevalence and cytotoxic activity of anti-HLA in blood donors with different medical histories to evaluate a potential risk of post-transfusion immune complications. Data were analyzed according to different normalized background cutoffs (1.5, 2.2; and the high cutoffs-10.8 for I class and 6.9 for II class anti-HLA). RESULTS: We observed that anti-HLA may be present in 36% of donors, and even in up to 73.6% of risk groups. Significant risk factors included female sex (23.9% to 64.2% for different cutoffs) and pregnancy history (30% to 72.5%), regardless of the cutoff used in analysis, whereas sera from female donors showed lower cytotoxicity (panel reactive antibodies). Anti-HLA were also detected in men (3.7% to 37%), in donors after a transfusion (0% to 62.5%), and even with no known risk factors (3.8% to 26.9%). CONCLUSIONS: Luminex technology is a sensitive tool in anti-HLA detection, but consensus in measurement interpretation for blood donors is needed. Selection of blood products on the basis of medical history can be a useful alternative for routine testing of blood donors. The clinical significance of treatment of graft recipients with blood products requires further study; until then, more attention should be paid to possible complications.

Cytokine response in patients with chronic infections caused by Staphylococcus aureus strains and diversification of their Agr system classes.

This study aimed to describe the levels of circulating cytokine levels produced by Th lymphocytes (IFN-γ, IL-4, IL-10, IL-17A), as well as the levels of cytokines produced by monocytes/macrophages (TNF-α, IL-1ß, IL-12), in patients with chronic infections caused by Staphylococcus aureus strains, particularly in the context of the diversification of their Agr system classes. The studies were conducted on adult patients, including 50 patients with chronic suppurative dermatitis, 40 patients with chronic infections of the upper respiratory tract and 25 healthy individuals (control group). Blood serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). S. aureus was detected in cultures of suppurative dermal exudates or of pharyngeal smears. Classes of Agr systems in the S. aureus strains were identified using polymerase chain reaction (PCR). In both groups of patients, on average, levels of IFN-γ were doubled, while levels of IL-17A were increased by 2.5-fold, which, however, was not accompanied by increased levels of TNF-α or IL-12. The data indicate that the development of S. aureus infection among the studied patients was linked to an impoverished cytokine response of monocytes/macrophages, while that induced by the pathogen lymphocytes Th17/Th1 may be responsible for promotion of the chronic inflammatory response. In parallel, no quantitative or qualitative differences were disclosed between cytokine responses manifested by subgroups of patients infected with S. aureus strains belonging to class IV Agr, as compared to patients infected with strains of classes I to III Agr. Nevertheless, in the patients, strains belonging to class IV Agr prevailed, which points to the preferential relationship between the class and the pathogenicity of S. aureus.

The association between past Chlamydia pneumoniae infection and markers of chronic inflammation in obese women.

It has been widely accepted that obesity is associated with chronic, low-grade inflammation that affects the adipose tissue as well as the entire system. The aim of this study was to assess whether past Chlamydia pneumoniae infection influences obesity phenotypes and serum levels of low-grade inflammation markers in obese, healthy premenopausal women. The study was performed on 48 obese and 42 normal-weight women, aged 31.2 +/- 7.2 years. Serum levels of C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha) and its soluble receptor R2 (sTNF-R2), and interleukin 6 (IL-6) were measured. Body composition was assessed by bioimpendance. Insulin sensitivity was assessed by quantitative insulin sensitivity check index (QUICKI). The seroprevalence of C. pneumoniae infection was 69.1% and was similar in obese and normal-weight women (75.2% and 61.9%, respectively; P = 0.18). Obese women had higher CRP than healthy controls (P < 0.05). IL-6, TNFalpha, and sTNF-R2 showed no significant differences when comparing obese and normal-weight or C. pneumoniae infected and uninfected women. In multivariate regression analysis, fat mass (P < 0.001) and QUICKI (P < 0.01), accounting for 35% of the variance of CRP and C. pneumoniae infection, did not significantly contribute to this model (P = 0.51). In conclusion, past C. pneumoniae infection was not associated with changes in chronic inflammation markers in premenopausal obese women.

Soluble HLA class I molecules exert differentiated influence on renal graft condition.

The function of soluble HLA (sHLA) antigens in the process of immunoregulation and especially in graft tolerance versus rejection has not yet been established. It has been suggested that donor-derived sHLA may exert an immunotolerant influence on the graft. We sought to determine the role of sHLA class I in kidney graft survival by evaluating the influence of these molecules on allotypic lymphocytotoxic antibodies and the concentration of gamma interferon (INF-gamma). Analysis of sHLA was performed indirectly utilizing their ability to inhibit lymphocytotoxic reaction dependent on complement activation. To demonstrate the inhibitory properties of sHLA, we modified the NIH microcytotoxic test. Furthermore, we determined the concentration of INF-gamma in all sera samples for comparison with the intensity of the cytotoxic test. The comparison of the intensity of cytotoxic test inhibition with the concentration of INF-gamma revealed that high concentrations of this cytokine were associated with stronger inhibition of the cytotoxic test, thus with higher concentrations of sHLA class I molecules in recipient sera. We observed that high concentrations of sHLA class I molecules in recipient sera significantly inhibited cytotoxic reactions, which could contribute to a protective influence of sHLA on renal grafts. On the other hand, the observed increase of INF-gamma concentration might be caused by sHLA themselves, which would produce a detrimental influence on a transplanted organ. Therefore we concluded that the role of sHLA class I molecules in renal graft condition remains ambiguous.

Short-term storage of human haematopoietic cells. Influence of air and deoxyribonuclease I.

The aim of this study was to optimize strategy for ex vivo short-term storage of human cord blood and bone marrow haematopoietic cells. We report that the presence of air in the vials (1/2 of their volume), in which hematopoietic cells are stored, improves the survival of clonogenic progenitors. We observed that presence of air prevented a rapid decrease in the pH of storage medium. Similarly, a beneficial effect on cell survival and recovery also had an addition of Deoxyribonuclease I (DNase I). We observed that DNase I efficiently prevented cell clumping, and moreover, did not affect the clonogenecity of the haematopoietic progenitors. Therefore containers, in which haematopoietic cells are stored, should contain enough air (source of oxygen) and the storage medium itself should be supplemented with DNase I.

[Biocenosis of the vagina and infection with Chlamydia trachomatis]. / Biocenoza pochwy a zakazenie Chlamydia trachomatis.

The authors have examined 379 women for infection by Chlamydia trachomatis, performing vaginal smears and routine bacterial cultures. C. trachomatis was discovered in 33.2% of the women, most frequently accompanied by erosion of the collum, cervicitis and CIN-Ca. Women with C. trachomatis had the following levels of vaginal purity: 1-44.4%, 2-23.0%, 3 and 4-29.4%, 3.2% -leukocytes only. Leukocytes were present in significantly more women with level 1 of vaginal purity than in the control group. Additional infections (Gardnerella vaginalis, Streptococcus agalactiae, Candida albicans, Escherichia coli and Trichomonas vaginalis) were found in only a small percentage of women with C. trachomatis, just as in controls. The presence of leukocytes or level 1 of vaginal hygiene with leukocytes may favour C. trachomatis, just as in controls. The presence of leukocytes or level 1 of vaginal hygiene with leukocytes may favour C. trachomatis infection, therefore these cases should be subjected to a more thorough examination.