Abstract: Invasive fungal rhinosinusitis (IFR) is a life-threatening infection. Its onset is subtle and a late diagnosis leads to severe complications. Death may occur within a few weeks notwithstanding treatment. We describe a comprehensive pre- and post-operative approach to care for haematological patients with IFR. Five haematological patients with IFR were treated with systemic antifungal therapy and endoscopic surgical debridement of infected tissues, followed by amphotericin-B directly instilled in the sinuses by a new type of ethmoidal drainage. The IFR remitted in all cases; after 32 months of follow-up, three patients are still alive, and two have died of other causes. Two of the patients who experienced IFR progression to the brain at the IFR onset are still alive. The pharmacological and surgical approach with the post-operative local therapy by a new ethmoidal drainage system could support radical antifungal sinus treatment, thus improving the overall survival.
Abstract: Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder of iron metabolism, genetically heterogeneous. In JH, symptomatic organ involvement occurs as early as the second decade of life. Heart failure and/or arrhythmias are the most frequent causes of death. Phlebotomy is the safest, most effective, and most economic therapeutic approach in hemochromatosis patients but is not indicated during the treatment of severe congestive heart failure with unstable hemodynamic status. The treatment of iron overload in these prohibitive clinical situations has to be carried out using iron chelators. We report a case of heart failure in the setting of unrecognized juvenile hemochromatosis successfully treated by the simultaneous administration of deferoxamine and deferiprone. To our knowledge, this is the first patient affected by JH treated with combined chelation regimen.
Abstract: This case report describes the previously-unreported clinical course of a patient with a so-called incomplete systemic lupus erythematosus (SLE), i.e. symptoms related to one organ system only, together with the presence of ANA. He had an indolent course initially and developed, 6 months after the first symptoms, a severe disease with rapid appearance of major and unusual manifestations. The possibility of fast progression and a grave course of an incomplete SLE should be kept in mind. This report is meant to heighten awareness of such an atypical presentation so that prompt and aggressive immunosuppressive therapy may be instituted.
Abstract: BACKGROUND/AIMS: Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8(+) and CD4(+) T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects. METHODS: Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3(+)CD8(+) and CD3(+)CD4(+) subsets. RESULTS: The patients studied showed a significant decrease of total lymphocyte count, T CD4(+)CD3(+), CD28(+), CD8(+)CD28(+) lymphocytes and natural killer (NK) CD56(+)CD16(+)CD3(-) cells. The reduction of CD28(+) and CD8(+)CD28(+) lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3(+)CD8(+) subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population. CONCLUSIONS: The association of a decreased number of T CD8(+) cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.
Abstract: Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV-1) before 1986 through contaminated plasma products are currently healthy, with CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched hemophiliacs infected in the same period but who have progressive HIV disease (progressors) and one additional slow-progressing individual were also studied. One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs, respectively, were found in LTNPs compared with progressors. Plasma and cell-associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for viral isolation from PBMCs or who were positive only after removal of CD8+ cells. No substantial differences were observed in the in vitro production of chemokines including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV isolation was simultaneously accomplished exclusively after removal of CD8+ cells. Low levels of HIV load and replication in peripheral blood are the strongest correlates of nonprogression in this small number of infected hemophiliacs.
Abstract: We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups.
Abstract: We compared the frequencies of HLA antigens in two matched groups of 31 HIV-seronegative and 31 HIV-seropositive haemophiliacs, exposed during the years 1981-85 to comparable amounts and batches of presumably infectious clotting factor concentrates. The frequency of A2 was significantly higher in HIV-seropositive than in seronegative haemophiliacs, with a relative risk (RR) of seroconversion of 3.92, whereas both Bw52 and DR4 were negatively associated with it. We also studied the distribution of HLA antigens in a larger group of 76 HIV-seropositive haemophiliacs, who were at different clinical stages of HIV infection (CDC classes II-IV) but were comparable for age and time elapsed since seroconversion. DR3 and DQw2 antigens were, particularly when concomitantly present, associated with a high risk of developing symptomatic HIV infection (RR = 11.79 and 25.33). Our data suggest that the HLA region controls susceptibility to infection with HIV and its progression to symptomatic disease in Italian haemophiliacs.
Abstract: In this study we investigated whether the interindividual variability of lymphocyte sensitivity to cyclosporin A (CsA) could be controlled by the HLA region. The models used were the in vitro primary and secondary autologous (AMLR) and allogeneic mixed lymphocyte (MLR) cultures of cells from 32 healthy subjects from our HLA reference panel. Our results show that CsA inhibited primary allogeneic MLR to a much greater extent than primary AMLR (-81 +/- 2% vs -38 +/- 8%, P less than 0.001). The same pattern was observed when cells harvested from CsA-treated primary cultures were rechallenged in secondary cultures with the original sensitizing stimulator cells (-40 +/- 6% vs -17 +/- 9%, P less than 0.05). No differences were observed in primary autologous and allogeneic cultures among responders of different HLA phenotypes. In contrast, the secondary responses did vary according to the HLA types: in secondary AMLR, CsA-priming did not lower, or even enhance, the proliferative responses of DR5+ and/or DR2+ lymphocytes (+7 +/- 13%), whereas it significantly lowered the responses of DR2-5- cells (-46 +/- 8%). In secondary MLR, lymphocytes proliferation was lowered by CsA-priming in all but DRW11(5)+ subjects (-45 +/- 7% vs +2 +/- 23%, P less than 0.05). It is concluded that the individual HLA phenotype influences the pattern of lymphocyte sensitivity to CsA.
Abstract: Thirty-one AIDS patients were typed for HLA A, B, C, and DR antigens. We confirmed that frequency of B35 is significantly higher in patients than in controls. No significant frequency differences in other HLA antigens were found. The analysis of HLA distribution in AIDS patients by risk categories suggests that B35 is a major risk factor, primarily mainly for patients belonging to the category of intravenous (IV) drug addicts.
Abstract: Peripheral blood mononuclear cells (PBMC) from 40 normal individuals, 20 men and 20 women, divided according to age were evaluated for their ability to mediate natural killer (NK) cytotoxicity, using the K562 erythroleukemic cells as target. The results of a specific 51Cr release assay demonstrated that NK activity was greater in men than in women. There was a significant correlation between NK activity and the percentages of Leu 11a+ cells in younger women, but not in the other groups and no correlation between NK activity and Leu 7+ cells.
Abstract: To investigate the contribution of genetic susceptibility to infection with human immunodeficiency virus, 50 subjects with lymphadenopathy syndrome (LAS) and 7 subjects with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma were typed for HLA A, B, C, and DR antigens. The frequency of B35 was significantly higher in LAS patients who progressed to AIDS than in those who did not or in healthy controls. The association between DR5 and AIDS/Kaposi's sarcoma was also confirmed in these patients.
Abstract: Studying families of schizophrenic patients, we observed that the risk of developing the overt form of the illness could be enhanced by some factors. Among these various factors we focused our attention on a biological variable, namely the presence or the absence of particular HLA antigens: partitioning our schizophrenic patients according to their HLA structure (i.e. those with HLA-A1 or CRAG-A1 antigens and those with HLA-non-CRAG-A1 antigens, respectively), revealed different illness distribution in the two groups. From a genetic point of view, this finding suggests the presence of heterogeneity in the hypothetical liability system related to schizophrenia and we evaluated the heterogeneity hypothesis by applying alternative genetic models to our data, trying to detect more biologically homogeneous subgroups of the disease.
Abstract: We have examined the allogeneic mixed lymphocyte reaction (MLR) and autologous mixed lymphocyte reaction (AMLR) stimulating activities of T cells precultured in vitro with soluble allogeneic or autologous HLA-DR antigens. These cells (Ts) are known to suppress the human MLR: this suppression is specific in that it occurs only when stimulator cells have the same HLA-DR antigen as that used to induce differentiation of suppressor cells. Ts cells express new membrane specificities; they can be separated by immunoabsorption into two populations: Ts enriched (Tx+; with suppressive activity) and Ts depleted (Ts-; with helper function). In the present study, we have demonstrated that both Ts cell subsets activated by soluble HLA-DR alloantigens are able to stimulate both MLR and AMLR. Ts cells activated by soluble autologous HLA-DR antigens are able to stimulate MLR, but not AMLR.
Abstract: We investigated HLA antigen and haplotype frequencies in 47 couples with primary recurrent abortions of unknown origin, in 65 fertile couples, and in a control panel of 98 males and 92 females. A significant increase of HLA-B17 was found in abortion couples in comparison with fertile couples. No difference between abortion and control fertile couples was observed regarding HLA sharing.
Abstract: Peripheral blood lymphocytes from 15 healthy subjects, selected on the basis of their HLA types, were cultured in vitro in the presence of PHA and of a number of drugs which bind adrenergic or dopaminergic receptors (dopamine, norepinephrine, chlorpromazine, haloperidol, propranolol and apomorphine). The results obtained are consistent with an interference between HLA-A1 and cross-reacting specificities and the effect explained by these drugs on the lymphocyte activation by PHA. The possibility is suggested that HLA-A1 and cross-reacting antigens interfere with the binding of such drugs to the cell membrane receptors.
Abstract: Human MLR-specific suppressor T lymphocytes were induced by in vitro cultivation of human peripheral T lymphocytes in the presence of soluble HLA-DR alloantigens isolated from normal serum. The suppression is specific in that responder cells autologous to the suppressor cells respond to allogeneic stimulating cells that express the same HLA-DR specificity as that recovered from serum and used to induce the suppressor cells. This antigen-specific suppressor T cell population could be divided into suppressor and non-suppressor subpopulations as a function of adherence to a 6MB Sepharose immunoadsorbent coated with the inducing HLA-DR soluble antigen. As a consequence of activation by soluble DR antigen, the suppressor T lymphocyte population as well as the column-enriched suppressor subpopulation express new membrane specificities that can be recognized by antisera from pluriparous women. The specificities that are recognized are not found on autologous, unstimulated B and T cells, nor do they appear to recognize conventional HLA-A,B,C or DR determinants.
Abstract: Human T lymphocytes precultured for 36 hr in the presence of soluble HLA-DR antigens suppress the MLR response of autologous peripheral blood lymphocytes to allogeneic stimulating cells. The suppression is DR antigen-specific in that it appears that the MLR stimulating cell donor and the soluble suppressor-inducing antigen must share DR specificities. The soluble DR antigens were fractionated from the sera of normal donors using QAE-Sephadex chromatography and CNBr-activated Sepharose immunoadsorption. Similarly prepared HLA-A and -B antigens failed to induce suppressive activity. The suppressive activity of DR-antigen cultured T cells is resistant to mitomycin C treatment and, further, the antigen specificity is maintained with or without mitomycin C treatment. The kinetics of suppressor cell induction as well as the kinetics of suppression in the test MLR cultures are presented. The implications of these results are discussed.
Abstract: The interference of chlorpromazine (CPZ) and several preincubated CPZ metabolites on the lymphocyte absorption of antibodies directed against HLA-A1 and other nonrelated HLA specificities were investigated. Both CPZ and metabolites 7-OH-, Nor1-, and Nor2-CPZ were found to interfere with the specific absorption of anti-HLA-A1 antibodies. The meaning of such a result is discussed.
Abstract: HLA phenotype distribution was investigated in 91 affective patients. Significant increases over those of the control population were found in HLA-A 29 and in Bw 22 frequencies, while A 10 and A 30 were decreased. No significant difference was shown between the two clinical subgroups (41 unipolar patients and 50 bipolar ones). On comparing our data with those from other authors, Bw 16 was significantly increased. However, a high degree of heterogeneity was also shown for this antigen. Of some interest is the finding that relapsed and non-relapsed patients during long-term lithium therapy display diverging HLA phenotype distributions, with B 5 increased among the non-relapsed subjects.
Abstract: When a group of 104 aged subjects was screened for autoimmune reactions, positive reactions for the rheumatoid factor and/or autoantibodies (ANA, anti-thyroid, PCA, anti-smooth muscle, anti-mitochondria) were recorded in 40.4%. Immunological functions were studied in 32 positive aged subjects, 32 age- and sex-matched negative controls, and 32 young subjects. Some differences attributable to the process of aging were quite evident, such as a depression in the percentage of E rosette forming peripheral lymphocytes and in their response to PHA, and an increase in the percentage of IgG-bearing peripheral lymphocytes and in the serum levels of IgA and three complement fractions (C'3, C'4, and C'3-PA). No clear-cut picture was noted when autoimmunity-positive and -negative, aged subjects were compared. However, some differences between sexes suggest that autoimmune reactions are linked to a depressed T cell function mainly in males, whereas the reverse is true for females.
Abstract: The effect of sera from pregnant women on the percentage of spontaneous rosette-forming peripheral lymphocytes was investigated. Pregnancy lymphocytes displayed a significantly lower capacity to bind SRBC than control male lymphocytes. However, after an exhaustive washing, it was possible to demonstrate a significant increase of spontaneous rosettes formed by pregnancy lymphocytes. It was found that the incubation of pregnancy-washed lymphocytes with pregnancy but not homologous male serum restored to depressed levels the values of rosette-forming peripheral lymphocytes. This blocking activity was significantly higher with autologous serum than homologous pregnancy serum. Control lymphocytes were unaffected both by washing and by incubation with pregnancy sera. The blocking activity was found in the same ion-exchange chromatography fraction of pregnancy serum where paternal HLA antigens could be demonstrated, and was reproduced by a soluble HLA preparation from the husband's lymphocytes.
Abstract: In this work T-enriched lymphocyte populations (obtained from Ig-anti-Ig-Degalancoated columns) were studied for their surface markers, especially for Fc and complement receptors, before and after a pulse-PHA-stimulation. It has been demonstrated that activated T lymphocytes express on their surface both of these markers in high percentage. The hypothesis is discussed that B and T lymphocytes differ only with regard to the presence of surface immunoglobulins or the ability of forming spontaneous rosettes. On the contrary the other surface markers may probably be expressed when needed functionally by the cells.
Abstract: The HLA-SD phenotype distributions of hebephrenic and paranoid schizophrenics, and of the two groups combined, in an Italian population and in a combined group from the Swedish population have been analyzed statistically. There is a significantly decreased frequency of HLA-A10 in all of these. Theae are some preliminary indications of an increased frequency (a positive association) for some of the other antigens of the HLA-SD series, but there is insufficient data at present for evaluating the significance of these findings. Differences between hebephrenic and paranoid schizophrenics have been detected.
Abstract: Twenty-two patients with the Lennox-Gastaut syndrome and their families were examined for HL-A antigens by the microlymphocytotoxicity test. The antigen HL-A7 belonging to the HL-A locus showed a significantly increased frequency (p less than 0.0005) both in parents and in patients. The same antigen showed a significantly altered segregation in patients but a normal one in healthy siblings. Another antigen of the second HL-A locus, HL-A12, did not display a normal segregation in our patients, in whom it was nearly not represented.
