Jacek Roliński

T helper 1- and T helper 2-type cytokine imbalance in pregnant women with pre-eclampsia.

OBJECTIVES The purpose of our study was to investigate T helper 1/T helper 2 balance in pregnant women with pre-eclampsia. STUDY DESIGN 18 patients with pre-eclampsia and 20 healthy pregnant women were included in the study. Peripheral blood mononuclear cells (PBMC) were stimulated with phytohaemagglutinin (PHA) for 48 h. Cytokine: interleukin-2 (11-2), interferon-gamma (IFN-gamma) and interleukin-10 (I1-10) concentrations in culture supernatants were determined using the ELISA method. Statistical analysis was performed using a standard non-parametric Mann-Whitney U-test. RESULTS We found that in pre-eclamptic patients PHA-stimulated 11-2 and IFN-y production was significantly higher (P<0.001) and I1-10 production significantly lower (P<0.005) in comparison with the control group. CONCLUSION These results could suggest that there is Th1/Th2 imbalance in pre-eclamptic patients with predominant Th1-type immunity.

The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients

Darmochwal‐Kolarz D, Rolinski J, Leszczynska‐Gorzelak B, Oleszczuk J. The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients. AJRI 2002; 48:381–386

T type 1/type 2 subsets balance in B-cell chronic lymphocytic leukemia: the three-color flow cytometry analysis

The impairments in immune cell functions as well as changes in cytokine network are the cause of malignant cell accumulation and secondary immune deficiencies in B-cell chronic lymphocytic leukemia (B-CLL). To broaden the knowledge of immune system in B-CLL we tried to evaluate the Th1/Th2 and Tc1/Tc2 balance in B-CLL patients in comparison with healthy individuals and changes of this pattern during disease progression. The three-color flow cytometry technique was used to analyze IL-4 and IFNgamma expression in peripheral blood CD3+CD4+ and CD3+CD8+ cells. The results indicate the dominance of T type 1 cells and T-cell-mediated immunity in B-CLL patients that is however shifted towards T type 2 during disease progression.

Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis

In order to evaluate the effects of vitamin D3 on monocyte-derived dendritic cells (DCs) of relapsing—remitting multiple sclerosis patients, DCs differentiation and maturation were evaluated in vitro based on surface phenotypic changes. The expression of CD14, CD83, CD1a, CD80, CD86, CD206 and C209 was analysed by fluorescence-activated cell sorting. The results reveal that vitamin D3 inhibits both the differentiation and maturation of DCs. Moreover, inhibits the secretion of IL 23/12p40 and increases the secretion of CCL2. The data suggest that one of the mechanisms of the beneficial action of vitamin D3 in multiple sclerosis may be associated with its influence on DCs.

Epstein-Barr virus-associated lymphoproliferative disorders.

The Epstein-Barr virus (EBV) is one of the most common human viruses, infecting more than 90% of the worlds adult population. In some individuals the interplay between EBV replication, latency and immune control can be disrupted and evokes prolonged proliferation of EBV-infected lymphocytes and their malignant transformation. Since its discovery as the first human tumor virus, EBV has been implicated in the development of a wide range of human cancers. The evidence for an association with EBV is the strongest for Burkitts lymphoma, NK/T cell lymphoma, nasopharyngeal carcinoma, Hodgkins lymphoma and for malignant lymphomas in immune incompetent patients. Additionally, certain epithelial cell tumors, such as gastric carcinoma and breast carcinoma, have been defined as EBV related. However, the virus may be encountered in other types of malignancies. The oncogenic potential of EBV is related to its ability to infect and transform B lymphocytes into continuously growing lymphoblastoid cell lines. EBV encodes a series of products mimicking several growth, transcription and anti-apoptotic factors, to usurp control of the pathways that regulate diverse homeostatic cellular functions. However, the exact mechanism by which EBV promotes oncogenesis remains unclear. The focus of this review is to summarize the current knowledge of oncogenic potential of the Epstein-Barr virus and its role in the pathogenesis of EBV-associated lymphoproliferative disorders.

Production of Proangiogenic Cytokines During Thalidomide Treatment of Multiple Myeloma

Recently a growing number of studies have suggested the efficacy of thalidomide (THAL) in the treatment of relapsed or resistant multiple myeloma. Some of these studies indicate that the thalidomide antimyeloma effect is associated with decreased vessel density. Here we first present our experience with THAL treatment and then focus on the determination of the role of proangiogenic cytokines during THAL therapy. Thirty relapsing or resistant multiple myeloma (MM) patients were treated with THAL at a median dose of 400 mg/daily. Eighteen responded to THAL therapy and 12 were resistant or intolerant to THAL. We determined the plasma level of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) as the main biological parameters associated with tumour angiogenesis. In addition I1-6 and TNF α levels were also assayed. Assessment of peripheral blood (PB) and bone marrow (BM) cytokine levels were done before and during THAL treatment at weeks 4 and 8 of therapy. In the responder group VEGF, bFGF I1-6 and TNF α concentrations were significantly decreased after four weeks of therapy both in PB and BM. In the non-responder group no significant changes in bFGF and VEGF levels were observed. However, a significant increase in IL-6 and TNF concentrations was evident. We conclude that the significant decrease of VEGF, bFGF, I1-6 and TNF α concentrations reflected response to THAL therapy. Also it seems that VEGF is a better marker of response to treatment than bFGF.

Immune Disorders in Hashimoto’s Thyroiditis: What Do We Know So Far?

This review of literature attempts to identify the factors that are involved in the pathogenesis of Hashimoto thyroiditis, an immune defect in an individual with genetic susceptibility accompanied with environmental factors. The frequency of Hashimotos disease is a growing trend and among Caucasians it is estimated at approximately 5%. The dysfunction of the gland may be clinically evident (0.1–2% of the population) or subclinical (10–15%). The pathology is diagnosed five to ten times more often in women than men and its incidence increases with the age (the peak of the number of cases is between 45 and 65); however, it can also be diagnosed in children. The pathogenesis of Hashimotos thyroiditis is still not fully comprehended. In the etiology of Hashimoto thyroiditis excessively stimulated T CD4+ cells are known to play the most important role. Recent research has demonstrated an increasing role of newly discovered cells such as Th17 (CD4+IL-17+) or T regulatory cells (CD4+CD25+highFoxP3+) in the induction of autoimmune disorders. The process of programmed cell death also plays an equally important role in the pathogenesis and the development of hypothyroidism.

Interleukin-18 levels in the plasma of psoriatic patients correlate with the extent of skin lesions and the PASI score.

Interleukin-18 is a cytokine with a possible role in the pathogenesis of psoriasis. We examined subpopulations of peripheral blood lymphocytes and their expression of activation markers and correlated this with plasma levels of IL-18 and clinical disease severity in patients with psoriasis. We included 12 patients with psoriasis who had a PASI score from 15 to 48 and compared them to controls. IL-18 plasma concentrations were determined with an enzyme-linked immunosorbent assay. We observed a significant correlation between the IL-18 levels and the area of skin affected with psoriasis and the PASI score. We also observed an increase in NK cells and memory helper CD45RO + /CD4+cells.

Antibody and Plasmablast Response to 13- Valent Pneumococcal Conjugate Vaccine in Chronic Lymphocytic Leukemia Patients - Preliminary Report

Background Chronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60–80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects. Methods Both groups were evaluated for: the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses and selected peripheral blood lymphocyte subpopulations including the frequency of plasmablasts before and after immunization. Results Adequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in the IgG2 subclass levels following vaccination (P = 0.0301). After vaccination, the frequency of plasmablasts was significantly lower (P<0.0001) in CLL patients in comparison to that in controls. Patients who responded to vaccination had lower clinical stage of CLL as well as higher total IgG, and IgG2 subclass levels. No significant vaccine-related side effects were observed. Conclusions PCV13 vaccination in CLL patients is safe and induces an effective immune response in a considerable proportion of patients. To achieve an optimal vaccination response, the administration of PCV13 is recommended as soon as possible following CLL diagnosis.

Lipoprotein (a) in patients with psoriasis: associations with lipid profiles and disease severity

Background  Lipoprotein (a) [Lp(a)] is a genetically determined molecule whose role has been implied in cardiovascular pathology, and whose levels have been reported to be elevated in patients with psoriasis.