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Biomedical subjects

F H Claas

Publications and source records attributed to F H Claas.

At least 217 records · Page 12Linked to original sources

Felty syndrome: autoimmune neutropenia or immune-complex-mediated disease?

Immunofluorescence on polymorphonuclear cells (PMN) of patients with Felty syndrome (FS) revealed increased amounts of IgG, IgA, and IgM bound to the PMN surface compared with PMN of patients with rheumatoid arthritis alone. A positive correlation was found between the score for surface-bound immunoglobulins on FS-PMN and the results of the Clq binding assay in FS sera. After preincubation with sera from 20 patients with FS, immunofluorescence on PMN from healthy controls (HC) showed that these cells had bound IgG, IgA, and IgM. However F(ab')2 fragments of IgG from FS sera did not bind to PMN, although the antigen-binding reactivity of the F(ab')2 fragments was maintained as shown by control experiments. Immunoglobulins eluted from FS-PMN failed to bind to HC-PMN, whereas the corresponding IgG of patients with autoimmune neutropenia was bound. Gel filtration of FS sera on Sepharose 4B showed that the binding of IgG in FS sera to PMN did not coincide with the 7S peak but occurred mainly in fractions containing larger material. No binding of IgA and IgM to HC-PMN was found after incubation with FS sera pretreated with polyethylene glycol (PEG) to precipitate immune complexes. These results indicate that in sera of patients with FS the PMN-binding reactivity of IgG, IgA, and IgM is due to the binding of immune complexes containing these immunoglobulins and not to presence of autoantibodies directed to antigens on the neutrophil surface.

Antigen-Antibody Complex↗

Humoral immunity in normal and complicated pregnancy.

To evaluate the role of some immunological phenomena involved in the pathogenesis of preeclamptic toxaemia, we studied the humoral immune reactivity in patients with preeclamptic toxaemia during the third trimester of pregnancy, and three days and six weeks after delivery. The results were compared with those of patients with intrauterine growth retardation and with uneventful pregnancy. During the third trimester, patients with complicated preeclamptic toxaemia had significantly lower IgG, CH50, C4 and C3 levels than normal pregnants. Post-partum levels of IgM were significantly higher than in all other groups of patients. Circulating immune complexes were not detectable by a C1q binding assay in patients and controls. However, with a conglutinin binding assay and a granulocyte phagocytosis test complexes were demonstrable in patients with complicated preeclampsia (incidence 44% and 33%, respectively). In addition, 66% of these patients showed deposits of immunoglobulins and complement components in superficial blood vessels of the skin biopsy, suggestive of the presence of tissue deposits of immune complexes. This was found in about 30% of the other patient groups and in none of control pregnants. Allo-antibodies to lymphocytes were present in 63% of complicated preeclamptic toxaemia patients and 22% of normal pregnants. Our data show several changes in humoral immune reactivity in preeclamptic toxaemia which may contribute to the pathogenesis of this disorder.

Adult↗

Influence of ultraviolet radiation treatment on the survival of heterotopic skin grafts in the mouse.

Isolated mouse tail skin was UV-irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove the Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When there was a total H-2 difference between donor and recipient, the UV-irradiated skin did not show a prolonged survival compared to control grafts. In the case of an I-region difference only, i.e., B10.AQR grafts onto B10.T (6R) recipients, a significant prolongation of the survival time was observed, whereas 50% of the UV-treated grafts were not rejected at all.

Animals↗

Thrombocytopenia and leucopenia with mianserin-dependent antibodies.

By indirect immunofluorescence specific mianserin-dependent antibodies were detected against platelets but not against granulocytes in the serum of a patient with thrombocytopenic purpura and mild leucopenia. A complement-mediated cytotoxicity assay demonstrated 70% lysis of granulocytes but no lysis of platelets, only when mianserin was added to the medium. We suggest that, at least in some patients, mianserin may cause blood disorders by an immunologically-mediated mechanism.

Aged↗

Model for detection of membrane-associated antigens on epithelial cells (HLA-A, -B, -C alloantigens and pemphigus antigens).

Incubation of skin explant culture with HLA-A, -B and -C alloantibodies results in detachment of cells at the periphery of the outgrowth. This detachment can be observed within 1 1/2 h, using the reflection contrast microscope. During the detachment of the epithelial cell, characteristic changes occur, such as disorganization of the filopodia and lifting up of the cell borders from the surface of the Petri dish. The same changes were seen using antibodies against pemphigus antigens.

Antigen-Antibody Reactions↗

IgM immune complexes, lymphocytotoxins, and rheumatoid factors in renal transplant recipients with CMV disease.

In studying 127 consecutive adult recipients of cadaver renal transplants, we found that the 23 patients who developed CMV disease produced IgM immune complexes as measured by a polyethyleneglycol precipitation (PEG) assay which coincided with symptoms of their illness. In addition to anti-CMV antibodies, PEG precipitated apparently non-specific antibodies such as lymphocytotoxins and rheumatoid factor (RF). The lymphocytotoxins were IgM antibodies that were not directed against HLA antigens and lysed granulocytes as well as lymphocytes but not platelets at 22 degrees C. Lymphocytotoxin production was correlated with HLA-DR 3 and 7 and with graft dysfunction during the CMV disease. The RF also were predominantly IgM antibodies that were detectable for only 3-8 weeks. The production of RF coincided with the initial rise in IgG anti-CMV antibody activity and some reacted with the Fab fragments of IgG raising the possibility that they could modulate the cellular or humoral immune response to CMV. Patients with RF tended to have severe CMV infections with pneumonia and graft dysfunction.

Adult↗

Antigenic composition of human renal vascular endothelium assessed by kidney perfusion.

Intravascular perfusion of healthy, viable human kidneys either with human sera or with monoclonal antibodies specific for individual HLA-A, B, DR or E-M antigens demonstrated that all of these antigens are exposed to circulating antibodies and thus can serve as stimuli or targets for immunologic mediators of renal transplant rejection. In addition, these antibodies could be recovered from the renal vessels by brief treatment with acid buffer.

Adult↗

[Thrombocytopenia due to antibodies induced by ticlopidine].

Ticlopidine is a new drug for the inhibition of the aggregation of platelets, which is used in arteriosclerosis. Here we describe a patient, who developed a thrombocytopenic purpura whilst using this drug. After stopping the drug, platelet counts normalized in two weeks. In the serum of this patient antibodies were found which reacted with the Ticlopidine exposed platelets of the patient after recovery and with those of healthy donors. These antibodies did not react when these platelets were exposed to tetrahydro-4,5,6,7,thiéno(3,2-c)pyridine, a metabolite of Ticlopidine. We conclude that after adherence of the drug to the platelet membrane, antibodies induced by Ticlopidine destroy the platelets as carriers of the drug.

Aged↗

Renal graft dysfunction during infection with cytomegalovirus: association with IgM lymphocytotoxins and HLA-DR3 and DR7.

Of 121 consecutive adult recipients of cadaver renal transplants who were treated with low dose steroids and azathioprine, 23 developed active cytomegalovirus infections. These 23 patients were divided into three groups on the basis of their symptoms related to the infection: five patients had no renal, respiratory, or haematological abnormalities; seven had renal dysfunction; and nine had renal dysfunction plus respiratory or haematological abnormalities. Two patients were regarded as a separate group because their infections occurred two to four weeks after graft nephrectomy. All but three of the patients produced IgM or IgG lymphocytotoxins during their infections. In the patients with mild infections and in control patients without infections, however, these lymphocytotoxins were predominantly IgG antibodies that were not precipitated by 3.5% macrogol (polyethylene glycol). In contrast, 12 of the 16 patients with renal dysfunction during their infections had broadly reactive IgM lymphocytotoxins. These IgM lymphocytotoxins lysed T as well as B lymphocytes at 22 degrees C and were precipitated by 3.5% macrogol, suggesting that they were circulating as immune complexes. Rheumatoid factors were found in sera from nine patients with cytomegalovirus infections, seven of whom developed leukopenia or pneumonia, or both, in addition to renal dysfunction. Some of these immune responses associated with cytomegalovirus infection in transplant recipients may be genetically controlled since 10 of 11 patients positive for HLA-DR3 or DR7 produced IgM lymphocytotoxins.

Adult↗

HLA-DRw6 and renal allograft rejection.

HLA-DRw6-positive patients are "high responders" to certain renal allograft antigens. A study was therefore conducted of the outcome of 247 first renal allografts in 74 DRw6-positive and 173 DRw6-negative recipients. The effectiveness of matching for HLA-DR determinants in both groups was also analysed. The one-year graft survival in DRw6-positive patients was 59% as compared with 75% in DRw6-negative recipients (p = 0.012). A striking difference between the two groups was that HLA-DR matching significantly improved renal allograft survival only in the DRw6-positive patients. In those patients the one-year survival of HLA-DR-identical grafts was 95% as compared with only 38% for 2-DR mismatched grafts (p = 0.009). In DRw6-negative patients only a slight beneficial effect of HLA-DR matching was observed (83% versus 72% at one year for the 0-DR and 2-DR mismatched grafts, respectively) (p greater than 0.05). These findings are clear evidence that DRw6-positive patients (about a quarter of the patients on the waiting list of Eurotransplant) should be given HLA-DR-identical kidney transplants only.

Graft Rejection↗

Expression of HLA-like structures on a permanent human tumor line PC-93.

A permanent human tumor-line PC-93 was HLA allotyped with the use of a complement-dependent cytotoxicity test supplemented with absorption experiments. In comparison with the peripheral blood lymphocytes of the patient, whose adenocarcinoma of the prostate was the origin of PC-93, remarkable differences were observed. The tumor line lacked the expression of the genetically appropriate HLA-A1, A2 and B15 antigens. Instead of these antigens, cross-reactive HLA antigens seemed to be expressed on PC-93, i.e. All, A28 and B17. Absorption experiments showed that the antibodies reactive with the neo-HLA antigens were not the same as those reactive with the specific HLA antigens. This alien expression of HLA-like structures was specific for the patients' prostatic tumor line, as EB-virus transformed B-lymphocytes of the patient expressed the genetically appropriate HLA antigens.

Absorption↗

All monocyte antigens are not expressed on renal endothelium.

Recently a tissue restricted antigen system, which is expressed on endothelial cells and monocytes (E-M antigens) but not lymphocytes, has been associated with kidney graft rejection. In screening sera from recipients of kidney, bone marrow or skin grafts for possible reactivity with endothelial cell antigens, we have found that all (13 of 13) endothelial reactive sera also reacted with monocytes, but that many (21 of 34) monocyte reactive sera did not react with endothelial cells. Additionally, one well-defined monoclonal antibody (M1/70), which was cytotoxic for human monocytes, neither stained renal endothelium nor was absorbed by renal endothelium when perfused through a human kidney. Thus, not all monocyte antigens appear to be expressed in high concentrations on renal vascular endothelium. This may explain why monocyte reactive antibodies do not always correlate with kidney graft rejection.

Absorption↗