Humoral immune response in patients with hemophilia

Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses.     

Identification of a subset of patients with scleroderma with severe pulmonary and vascular disease by the presence of autoantibodies to centromere and histone.

OBJECTIVES--The role of autoantibodies in the investigation and management of rheumatic diseases is well recognised. The objective of this study was to determine the clinical significance of the co-occurrence of antibodies to centromere and histone in serum samples from patients investigated for systemic rheumatic diseases. METHODS--Serum samples from 1316 consecutive patients were screened for antinuclear antibodies and the clinical findings in patients with antibodies to centromere alone were compared with those with antibodies to both centromere and histone. RESULTS--Twenty six patients had antibodies to centromere. Fourteen patients had antibodies to centromere alone and 12 patients had antibodies to centromere and histone. Four of the 12 patients with antibodies to centromere and histone had diffuse scleroderma with severe pulmonary or vascular disease. CONCLUSIONS--A subset of patients with scleroderma with antibodies to centromere and histone has been identified retrospectively, who have severe pulmonary or vascular disease. It will be of interest to follow up the clinical course of other patients with scleroderma who have both antibodies for the development of pulmonary or vascular disease.     

Practicability of protontherapy using compact laser systems

Protontherapy is a well-established approach to treat cancer due to the favorable ballistic properties of proton beams. Nevertheless, this treatment is today only possible with large scale accelerator facilities which are very difficult to install at existing hospitals. In this article we report on a new approach for proton acceleration up to energies within the therapeutic window between 60 and 200 MeV by using modern, high intensity and compact laser systems. By focusing such laser beams onto thin foils we obtained on target intensities of 6 x 10(19) W/cm2, which is sufficient to produce a well-collimated proton beam with an energy of up to 10 MeV. These results are in agreement with numerical simulations and indicate that proton energies within the therapeutic window should be obtained in the very near future using such economical and very compact laser systems. Hence, this approach could revolutionize cancer treatment by bringing the "lab to the hospital-rather than the hospital to the lab".     

An antigen in metaphase chromatin and the midbody of mammalian cells binds to scleroderma sera

Antibodies from 5 patients with systemic sclerosis reacted with an antigen localized to the metaphase chromatin, the cleavage furrow and the midbody of anaphase and telophase HEp-2 cells. The titer of antimidbody antibodies ranged from 1:160 to 1:1280. Four patients had systemic sclerosis and one had idiopathic Raynaud's phenomenon. In situ biochemical characterization of the antigen revealed that it was resistant to DNase I, micrococcal nuclease and RNase A, but was sensitive to trypsin treatment. The antigen remained insoluble in 400 mM acetic acid but was extracted from the cells with 400 mM hydrochloric acid. The antibody was not seen in sera from 2500 normal female blood donors, 120 patients with systemic lupus, 60 patients with rheumatoid arthritis, 15 patients with linear scleroderma or 25 patients with Raynaud's disease.     

Immunocytological studies of Epstein-Barr viral antigen and antibody in rheumatoid synovial fluids

Evidence for intra-articular immunity to Epstein-Barr virus (EBV) was sought in synovial fluids (SF) and SF phagocytes derived from patients with and without rheumatoid arthritis (RA). Antibody titres to EBV were not significantly different in SF of 32 RA and 25 non-RA patients. Whereas the majority of RA patients (69%) showed Ig-containing complexes (IC) in SF phagocytes, fluorescent antibody staining of these by anti-EBV serum was negative except with 6 RA patients. Extended analysis of the SF phagocytes of the latter, however, showed no EBV specificity in their IC, suggesting that these represented non-specific "pseudo-IC'. These studies do not support a role for EBV-containing IC in the propagation of rheumatoid synovitis and demonstrate that not all immunofluorescent inclusions in RA phagocytes (ragocytes) represent immune complexes.     

Detection of autoantibodies to ss-a/ro by indirect immunofluorescence using a transfected and overexpressed human 60 kd ro autoantigen in hep-2 cells

The objective of the study was to determine the sensitivity and specificity of an indirect immunofluorescence (IIF) assay using transfected HEp-2 cells to detect anti-SS-A/Ro autoantibodies in human sera. Seventy-three sera having SS-A/Ro autoantibodies as determined by double immunodiffusion (ID) and immunoblotting (IB) were tested by IIF on a HEp-2 cell substrate that had been transfected with a full-length cDNA encoding a human 60 kD SS-A/Ro autoantigen. Controls included 30 normal human sera and 50 sera with a variety of other antinuclear antibodies. Prototype human and rabbit sera directed against the 60 kD SS-A/Ro antigen produced intense speckled nuclear and nucleolar staining of transfected cells. Sixty-nine of 73 (95%) SS-A/Ro positive sera also produced this characteristic staining pattern. The endpoint autoantibody titers on transfected cells was fivefold greater than on untransfected cells. The 30 normal human sera and the 50 sera with other antinuclear antibodies did not produce this characteristic staining. Six of 32 (19%) unselected sera that were sent for autoantibody testing had reactivity with transfectants by IIF. Four of the six sera were confirmed to have anti-SS-A/Ro antibodies by ID and 5/6 by IB. By contrast, only three of these sera were scored as having a staining pattern compatible with SS-A/Ro antibodies by IIF on standard HEp-2 substrates. We conclude that SS-A/Ro autoantibodies can be detected by an IIF assay using a HEp-2 cell substrate transfected with a SS-A/Ro cDNA. This new substrate detects SS-A/Ro antibodies that were not identified on standard HEp-2 substrates and by other immunoassays.©1995 wiley-Liss, inc.