Introduction. Psoriasis is a T cell-mediated inflammatory disease in which pathogenesis T helper (Th) lymphocytes (Th1, Th17, and Th22) play an important role. The aim of the study was to assess the serum levels of some cytokines involved in the Th17 and Th22 responses in psoriatic patients. Material and Methods. The study comprised 60 psoriatic patients and 30 healthy controls. In the serum collected from psoriatic patients and healthy controls, the concentrations of IL-6, IL-12, IL-17, IL-20, IL-22, and IL-23 were examined with ELISA kits. Severity of psoriatic skin lesions was assessed by means of PASI, BSA, and PGA scores. Results. IL-6, IL-20, and IL-22 concentrations were significantly higher in psoriatic patients in comparison with the control group. The positive correlations between the concentrations of IL-22 and IL-20 and severity of psoriasis assessed with PASI and BSA scores as well as IL-17 and PASI score were found. There was also a positive correlation between IL-23 and IL-17 concentrations. Conclusions. Results of the conducted studies suggest that Th22 response may contribute to the skin and systemic inflammatory disease in psoriasis. It seems that early identification of soluble biomarkers and initiation of well-matched treatment may prevent exacerbation and progression of psoriasis.

Abstract. The status of the immune system of patients with B-cell chronic lymphocytic leukemia (B-CLL) is not yet sufficiently characterized. Clinically, B-CLL patients present immunodeficiency increasing along with disease progression and signs of autoimmunity. In the current study, we evaluated the expression of FOXP3 in CD4 + CD25 hi T regulatory lymphocytes (Treg) and their influence on immune response against tumor and viral antigens in the complex system of peripheral blood mononuclear cells. In 80 B-CLL patients, the frequency of Treg (CD4 + CD25 hi FOXP3 + ) cells was significantly higher in B-CLL patients when compared to healthy volunteers (HV) and increased with the progression of the disease (median: 8.24% in stage A, 11.24% in stage B and 12.57% in stage C according to the Binet classification). The frequency of Treg showed no correlation with prognostic markers such as ZAP-70, CD38 and HLA-G. Notably, Treg frequency correlated with serum levels of TNF (r 2 =0.45, p=0.001). T-cell immune responses against epitopes derived from the tumor-associated antigens survivin, fibromodulin and RHAMM as well as from the influenza matrix protein were evaluated. Functionally, higher frequencies of Treg correlated with decreased T-cell responses against viral and tumor antigens. In conclusion, we detected higher frequencies of Treg in B-CLL patients than in HV. Furthermore, Treg constitute the crucial mechanism of immunosuppression in B-CLL patients. IntroductionThe immune status of patients with B-cell chronic lymphocytic leukemia (B-CLL) is poorly characterized (1,2). Clinically, CLL patients present immunodeficiency, along with signs of autoimmunity (3). Several studies have aimed to characterize the immunity of B-CLL, however, results were ambiguous and difficult to interpret especially towards active immunotherapy for those patients (4). The graft vs. leukemia effect (5) as well as the 'spontaneous' remissions associated with an increased immunity against viral antigens (6) suggest that CLL cells may be targeted by a T cell-mediated immune response. Naturally occurring tumor-reactive T cells were found in some B-CLL patients (7). During disease progression, patients displayed signs of immunosuppression resulting in an impaired immune response against tumor-associated antigens (TAA) as well as against viral and bacterial antigens. Several immunosuppressive mechanisms allow CLL cells to escape from immunosurveillance. Recently, enhanced frequencies of CD4 + CD25 hi T regulatory cells (Treg) in B-CLL were reported by Beyer et al (8). Apart from CD4 + CD25 hi T cells, other immunomodulatory factors such as cytokines IL-10 and TGF-ß may suppress immune responses (9,10). Defects of immune response might be induced by a direct cell-cell contact suggesting the immunosuppressive role of the B-CLL cell itself that might be mediated by the expression of the non-classic human leukocyte antigen (HLA)-G protein (11). HLA-G released in its soluble (sHLA-G) form may also inhibit immune responses against TAA since sHLA-G in...

In this prospective randomized trial, we compared the efficacy and toxicity of cladribine (2-CdA) alone to 2-CdA combined with cyclophosphamide (CC) or cyclophosphamide and mitoxantrone (CMC) in untreated progressive chronic lymphocytic leukemia (CLL). Study end points were complete response (CR), overall response, minimal residual disease (MRD), progression-free survival, overall survival, and toxicity. From January 1, 1998 to December 31, 2003, 508 patients from 15 hematology departments were randomized. Compared with 2-CdA, CMC induced higher CR rate (36% vs 21%, P ‫؍‬ .004), and a trend for higher CR rate with CC was observed (29% vs 21%, P ‫؍‬ .08). Furthermore, the percentage of patients who were in CR and were MRD negative was higher in CMC compared with 2-CdA (23% vs 14%, P ‫؍‬ .042). There were no differences in overall response, progressionfree survival, and overall survival among treatment groups. Grade 3/4 neutropenia occurred more frequently in CC (32%) and CMC (38%) than in 2-CdA (20%) (P ‫؍‬ .01 and P ‫؍‬ .004, respectively). Infections were more frequent in CMC compared with 2-CdA (40% vs 27%, P ‫؍‬ .02).In conclusion, CMC used in first-line treatment of CLL results in a higher CR rate and suppresses MRD more efficiently than 2-CdA monotherapy, although associates with increased toxicity. No important differences in efficacy and toxicity were found between CC and 2-CdA regimens.

Menkes disease is an effect of ATP7A gene mutation in humans, coding the Cu-ATP-ase which is essential in intestinal copper absorption and its subsequent transfer to circulation. This mutation results in a deficiency of copper in all tissues except the epithelia of intestine and kidney tubules. Subcutaneous injection of copper ions is the main therapy for Menkes patients. Mosaic (Atp7a(mo-ms)) mice closely simulate the situation in Menkes disease. The aim of this study was to evaluate the changes in structure and element content in kidneys of mosaic mice after copper supplementation. Hematoxylin-eosin staining was used to analyze tissue morphology and atomic absorption spectrometry to estimate Cu and Zn content. X-ray microanalysis was performed to measure Na, Mg, P, Cl, and K content in the cells of the proximal and distal tubules. Copper administration lengthened the lifespan of the mutants but led to its high accumulation and results in severe kidney damage. Karyomegalia, necrosis of tubular and Bowman's capsule epithelium, lesions, and atrophy of glomeruli were observed in the treated mutants. Copper treatment afterwards led to sclerosis of glomeruli and tubules enhanced proliferation of epithelial cells and formation of both polycystic and papillary carcinoma patterns in kidney. We suggest that copper excess may impair the activity of Na(+)/K(+) ATP-ase in renal tubules of ms/- males. The content of Mg, P, and Cl in kidneys in mutants was also changed after copper administration.

Angiogenesis has been shown to substantially contribute to the progression of chronic lymphocytic leukemia (CLL). Neuropilin-1 (NRP1) represents a receptor for vascular endothelial growth factor (VEGF), which has been reported to be overexpressed in several malignancies. In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed. Earlier we described the specific Treg reduction during the therapy with thalidomide in vivo. Now we observe the reduction of the NRP1 expression on Tregs in vitro, thereby suggesting a possible target of thalidomide action. In conclusion, NRP1 might represent an interesting link between angiogenesis and tolerance mechanisms and represents interesting target for therapy.