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The serum levels of beta 2-microglobulin (beta 2-m) were determined in 80 intravenous drug addicts (IVDA) with acquired immunodeficiency syndrome (AIDS), in 128 HIV-positive IVDA with persistent generalized lymphadenopathy (PGL) and in 44 HIV-seronegative IVDA. Seventy-two out of 80 (90%) AIDS patients had elevated serum beta 2-m levels and high levels of beta 2-m were also found in 105 of 128 (82%) HIV-infected subjects without AIDS. The mean beta 2-m level was significantly higher in HIV-infected patients with PGL than in HIV-negative IVDA. Nine out of 64 (14%) PGL patients developed AIDS in a period of 24-54 months. In these patients the mean beta 2-m level (5.16 +/- 2.37 mg/l), obtained from sera stored at the first observation, was significantly higher than in the other PGL patients (3.40 +/- 1.03 mg/l); in particular, 5 out of 7 PGL patients with beta 2-m levels greater than 5.0 mg/l showed an advanced disease.

An impaired function of splenic macrophages, measured as the clearance rate of erythrocytes coated with IgG (E-IgG), was observed in 7 out of 8 cryoglobulinemic patients with severe urinary abnormalities and systemic symptoms, and in 0 out of 6 patients without urinary symptoms and only mild systemic signs of disease. The E-IgG clearance rate was not related to HLA or Rh phenotype, patients' age or disease duration. Moreover, longitudinal studies showed this parameter to be strictly related to disease activity. To investigate the nature of the defect, five series of analyses were planned using peripheral blood phagocytes (PBP) from 8 patients: a) detection of cell-bound immune material by using the antibody CE59 directed to the Fc fragment of IgG modified by the antibody-antigen reaction; b) cytofluorometric and/or radiometric analyses of the cell surface expression of HLA II, CR1 and FcR structures by means of specific monoclonal antibodies (MoAbs); c) electron microscopy (EM) examination of diverse combinations of cryoglobulins incubated with PBP from patients and normals; d) analysis of cryoglobulin-induced inhibition of E-IgG phagocytosis; e) measurement of the generation of chemiluminescence (CL) in response to Zymosan, Phorbol Myristate Acetate and n-Formyl-Methyonine-Leucine-Phenilalanine (n-FMLP). Patients' PBP were found to have a higher amount of cell-bound immune material as compared to normals (p less than 0.01). CR1 and FcR expression was not different from controls, whereas a slight increase in percentage of monocytes bearing HLA II structures was found in patients (p less than 0.05). Upon EM examination no obvious differences were found in the internalization capacity of cryoglobulins between patients and controls. The CL production was lower than normal (p less than 0.02), whatever stimulus used, with a maximal impairment for n-FLMP (p less than 0.005), the most specific test probe for cytoskeleton integrity. Finally, a remarkable cryoglobulin-induced inhibition of E-IgG phagocytosis was shown. A combination of saturation mechanisms and intracellular abnormalities could underlie the apparent discrepancy between E-IgG clearance defect and preserved potential of cryoglobulin internalization in cryoglobulinemia.

The effects of gliadin and glyc-gli on leukocyte chemiluminescence response, cytotoxic activity and locomotion were assessed in vitro. A dose-dependent increase in chemiluminescence response of neutrophils stimulated by Zymosan was observed by using gliadin at concentrations ranging between 1 and 20 micrograms. By increasing glyc-gli concentrations, a bimodal response was observed with an enhancement up to 50 micrograms/ml, followed by dose-dependent suppressive effects. The cytotoxic activity of a suspension of peripheral blood mononuclear cells on the human myeloid line K562 was assessed in a Chromium release assay. By pretreating effector cells with optimal doses of gliadin (5 micrograms/ml) or glyc-gli (50 micrograms/ml), an enhancement of cytotoxic activity, similar to that of the gamma-Interferon, could be achieved. Finally glyc-gli was found to elicit neutrophil chemokinesis. The possible implications of these findings in diseases characterized by gluten intolerance are discussed.

Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.

We analysed the possible mechanisms responsible for the functional abnormalities reported on phagocyte cell function in IgA nephropathy patients. The oxidative metabolism by the superoxide anion ferricytochrome C reduction test on monocytes and the chemiluminescence response on neutrophils was examined in 32 patients. Moreover the expression of cell membrane structures involved in immune response and phagocytosis (i.e. Fc receptors and HLA class II antigens) was evaluated cytofluorimetrically using specific monoclonal antibodies. Our own results did not show striking differences in oxidative potential and phenotype of patients' phagocyte cells as compared with healthy controls. However a HLA class II-associated structure was found to be quantitatively more expressed in patients' monocytes than in normal controls (P less than 0.005). These findings suggest that the defective phagocyte system function reported in IgA nephropathy patients is not simply due to a loss of cell surface receptors, nor to abnormalities in intracellular metabolic pathways implying oxygen consumption. The increase in expression of some HLA class II structures, often associated with the presence of circulating IgA immune complexes, probably reflects a protracted immunological stimulation.

Serum beta 2 microglobulin (beta 2-M) levels were determined in patients with Acquired Immunodeficiency Syndrome (AIDS), AIDS Related Complex (ARC), Persistent Generalized Lymphadenopathy (PGL), healthy intravenous drug addicts (IVDA) and heterosexual controls. Seventy-eight out of 79 AIDS patients (98.7%) exhibited elevated beta 2-M levels. High levels of beta 2-M were also found in 83 of 100 (83%) of PGL/ARC patients and in 24 of 56 (42.8%) healthy IVDA. Patients with AIDS had significantly higher mean beta 2-M levels when compared with all other groups. The mean levels of PGL/ARC patients were significantly higher than those of healthy IVDA and the mean levels for healthy IVDA significantly differ from those of the heterosexual controls. After 2-24 months of follow up three out of four PGL/ARC patients whose serum beta 2-M was greater than 8.0 mg/l developed AIDS.