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Abstract Background About 30% of the population worldwide are infected with the protozoan parasite Toxoplasma gondii. Latent toxoplasmosis has many specific behavioral and physiological effects on the human organism. Modified reactivity of the immune system has been suggested to play a key role in many of these effects. For example, the immunosuppression hypothesis explains the higher probability of the birth of male offspring observed in Toxoplasma-positive humans and mice by the protection of the (more immunogenic) male embryos against abortion. Methods Here we searched for indices of immunosuppression in Toxoplasma-positive subjects by comparing clinical records of immunology outpatients. Results Our cohort study showed that the male patients with latent toxoplasmosis had decreased and the Toxoplasma-positive women had increased leukocyte, NK-cell and monocyte counts in comparison with controls. The B-cell counts were reduced in both Toxoplasma-positive men and women. The difference between Toxoplasma-positive and Toxoplasma-negative subjects diminished with the decline of the specific Toxoplasma antibody titre (a proxy for the length of infection), which is consistent with the observed decreasing strength of the effect of latent toxoplasmosis on human reproduction. The prevalence of toxoplasmosis in 128 male patients was unusually low (10.9%) which contrasted with normal prevalence in 312 female patients (23.7%) and in general population Prague (20-30%). Conclusions Latent toxoplasmosis has immunomodulatory effects in human and probably protects men against some classes of immunopathological diseases. The main limitation of the present study was the absence of the data on the immunoreactivity of immune cells subpopulations. Therefore further studies are needed to search for indices of immunosuppression in human using more specific markers.

As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.

Calprotectin (MRP8/14, S100A8/S100A9, 27E10 antigen) is a heterodimer of two calcium-binding proteins present in the cytoplasm of neutrophils and expressed on the membrane of monocytes. Upon neutrophil activation or endothelial adhesion of monocytes, calprotectin is released and may be detected in serum or body fluids as potentially useful clinical inflammatory marker. The soluble form of calprotectin provides both bacteriostatic and cytokine-like effects in the local environment. When calprotectin metabolism is affected on a systemic level, the zinc-binding properties of protein may induce severe dysregulation of zinc homeostasis with severe clinical symptoms. The distribution of membrane form of calprotectin is restricted to monocytes and immature macrophages and the presence of calprotectin-positive infiltrating cells reflects the influx of mononuclear phagocytes to the site of inflammation. Calprotectin expression and release seems to be of particular importance in immune and immunopathological reactions.

Recent literary data suggest that antibodies to HLA antigens undetectable by the standard complement-dependent cytotoxicity test may cause not only chronic, but also acute immunological complications after kidney transplantation. The aim of this study was to investigate the significance of non-cytotoxic antibodies to HLA antigens for the development of immunological complications and a worse graft prognosis after first kidney transplantation. Sera before and early after transplantation from 120 first kidney recipients were analyzed by flow cytometry (FCXM), ELISA and the standard complement-dependent cytotoxicity (CDC) test. Pre-transplant FCXM negativity was related to a lower incidence of rejection episodes in the first post-transplant year ( P<0.01). A significant association between acute rejection and the presence of antibodies to HLA class II antigens before and after transplantation was also found ( P<0.05). Our study supports the findings of other centers of the detrimental role to the kidney graft played by anti-HLA antibodies undetectable by the classical CDC test.

Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF-beta1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF-beta1 plasma levels, cyclosporine levels, plasma lipids, HLA-mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF-beta1 tissue expression is linked with chronic vasculopathy.

Objectives: MRP8/14 is a heterodimer of two myeloid calcium-binding proteins associated with different types of acute inflammatory processes. We studied MRP8/14 together with procalcitonin (PCT) serum levels in order to diagnose infectious complications or the rejection process affecting kidney or heart allograft., Methods: A total of 419 serum samples was evaluated. MRP8/14 levels were measured by ELISA (BMA Biomed), PCT by a sensitive immunoluminiscent assay ILMA (Brahms Diagn.), Results: Both parameters showed very low basal levels in healthy subjects (range 303-1,660 ng/ml of MRP8/14; less than 0.08 ng/ml of PCT). A rapid increase in serum levels occurred in response to bacterial infections (MRP8/14 up to 6,230 ng/ml; PCT up to 297 ng/ml). Serum PCT concentration remained low in the presence of kidney allograft rejection, where MRP8/14 levels were increased. An uncomplicated outcome of kidney or heart transplantation did not change basal serum MRP8/14 and PCT levels., Conclusions: We conclude that 1) both MRP8/14 and PCT are very sensitive markers of complications in organ transplant recipients (normal values in uncomplicated outcome) 2) combination of both parameters is useful to discriminate between rejection (increased MRP8/14 with normal PCT) and systemic bacterial infection (both parameters increased).

Objective: The aim of this study was to characterize patient antibodies before and after cadaver and/or living-donor kidney transplantation and to correlate these data with the clinical course after transplantation., Methods: Sera from 69 cadaver, 9 living-related and 2 patients waiting for living-donor kidney transplantation were analyzed by the complement dependent cytotoxicity (CDC) test, flow cytometry (FCXM) and ELISA., Results: FCXM revealed that 15.0% of patients before transplantation and 16.7% after transplantation had antibodies to donor cells. 10.3% patients were positive before and after transplantation (+/+), while 6.8% developed antibodies early after transplantation (-/+). Analysis of the specificity of those antibodies by ELISA showed that it was directed to: 1) mismatched donor HLA antigens 2) antigens belonging to the same cross-reacting group (CREG) as the mismatched donor antigens 3) HLA antigens not expressed by donor cells or, probably, to non-HLA antigens., Conclusion: Anti-HLA antibodies were detected in patients before and after transplantation and in most cases their anti-HLA specificity could be determined. Fast and precise characterization of antibodies in patients before and after transplantation can be performed by both sensitive methods--FCXM and ELISA--which may help predict the onset of immunological complications and, consequently, improve the prognosis after organ transplantation.

Alveolar macrophages (AM) originate from blood monocytes and, during the maturation process, undergo functional and morphological changes which are also reflected in their phenotypic pattern. Among the macrophage membrane antigens, adhesion molecules of the integrin family are particularly important for effector functions and cell-cell interactions. The aim of this study was to analyse the membrane expression of selected integrins by AM recovered from bronchoalveolar lavage (BAL) as compared to their precursors, peripheral blood monocytes (PBM). The cells were stained using a sensitive immunoperoxidase assay with 10 different monoclonal antibodies. The data showed a higher expression by AM than PBM of all but one of the studied adhesion molecules. The only exception was CD11b (Mac-1, CR3) which showed a higher expression in PBM than in AM. Several molecules, for example, CD49d (VLA-4), CD51 (vitronectin receptor), and CD54 (intercellular adhesion molecule-1, ICAM-1) were found to be upregulated by AM in patients with a lymphocytic pattern of BAL. In contrast, the phenotype of PBM does not show any changes in these patients. In conclusion, we have demonstrated differences in the expression of integrins between AM and PBM which can be partially responsible for some of their functional differences.

The phenotype of alveolar macrophages (AMs) is known to be modulated during pathological immune reactions in the lung. In this study, we wanted to determine the relationship between the AM phenotype and changes in the proportions of the various immune cells in bronchoalveolar lavage (BAL). BAL was performed in 76 consecutive patients, including 32 with sarcoidosis, 8 with idiopathic pulmonary fibrosis, 9 with pneumoconiosis, 13 with other respiratory disorders, and 14 controls without evidence of interstitial lung disease. The phenotype of AMs was studied by a panel of 15 monoclonal antibodies against various myeloid antigens, and was correlated with the proportions of cells obtained by BAL. The percentage of BAL lymphocytes showed a relationship with the expression of macrophage antigens in 11 out of 15 antigens studied (all except adhesive molecules CD11a, CD11c, CD18 and the antigen 25F9 present on mature macrophages). Furthermore, the CD4/CD8 ratio of BAL T-lymphocytes correlated with the AM expression of CD54 (intercellular adhesion molecule-1 (ICAM-1)), RFD1 (marker of dendritic cells), and CD71 (transferrin receptor). In samples with an increased number of bronchoalveolar neutrophils, the subpopulation of 27E10 positive AMs (inflammatory acute phase macrophages) was increased. Eosinophils in BAL were not associated with a significant increase in AM membrane antigen expression. Prominent changes of the AM phenotype were found in active sarcoidosis showing lymphocytic alveolitis, with more frequent expression of CD54, KiM2, CD71, CD11b and RFD9. In conclusion, this study shows that the phenotype of AMs is related to the type and intensity of the immunopathological reaction in the lung, and correlates with the proportions of bronchoalveolar cells.