W. M. Baldwin

Vascular endothelial alloantigens in renal transplantation.

Revue detudes faites chez lhomme et chez lanimal: la composition alloantigenique de lendothelium dans le rein; les reactions produites lors de transplantations; les antigenes endotheliaux definis par anticorps monoclonaux. Importance dune meilleure recherche sur ces phenomenes pour la comprehension de la pathogenese du rejet

Expression of HLA-DR on T lymphocytes following renal transplantation, and association with graft-rejection episodes and cytomegalovirus infection

The expression of HLA-DR by T lymphocyte subpopulations recognized by monoclonal antibodies and flow cytometry was monitored in 10 normal controls, 15 patients on hemodialysis, 25 recipients of a renal allograft with stable graft function, 16 transplant recipients suffering rejection episodes, and 4 transplant recipients with cytomegalovirus (CMV)4 infection. No significant differences in HLA-DR expression were observed in the OKT4-reactive subpopulation among these controls and patients. In the 16 patients who suffered rejection episodes a significant increase in HLA-DR expression by OKT8-reactive cells was observed. In the 10 patients in whom rejection episodes occurred later than 1 week after transplantation, the percentage of OKT8-reactive cells that expressed HLA-DR was dramatically increased 2-6 days before the onset of clinical symptoms of rejection (P less than 0.001 Students t test). When the rejection episode responded to treatment, expression of HLA-DR on the OKT8-reactive cells decreased--whereas in 3 patients who lost their grafts because of irreversible rejection, expression of HLA-DR remained elevated. In addition, the 4 patients with CMV infection had increased percentages of OKT8-reactive cells that expressed HLA-DR (P less than 0.001 Students t test). This increase in expression of HLA-DR coincided with the onset of clinical symptoms of the CMV infection, and the expression of HLA-DR returned to normal values after the titers of antibodies to CMV had increased significantly and symptoms of infection had disappeared.

Serum immune complexes containing IgA appear to predict erosive arthritis in a longitudinal study in rheumatoid arthritis.

Fifty seven patients with rheumatoid arthritis (RA) were studied longitudinally, and the presence of rheumatoid factor (RF) and various types of immune complexes (IC) was correlated with joint activity and the presence of extra-articular features (EAF). In a cross sectional study it was found that the levels of circulating IC and RF correlated significantly with joint disease activity and the presence of EAF. Longitudinally, levels of IC measured by the C1q binding activity and IC containing IgG and IgM correlated significantly with fluctuations in joint disease activity, whereas IC containing IgG and IgA correlated with the occurrence of EAF. RF and IC levels, however, did not predict the clinical course of the disease. IC containing C3 and C4 were found infrequently and were only present in patients with active rheumatoid vasculitis (RV). The continuous presence of these IC appeared to be linked to the recurrence of vasculitis, irrespective of treatment. Significantly more erosions of hands and feet were found after one year follow up in those RA patients who presented early (disease duration less than one year) who initially had a raised serum IgA IC level (r = 0.72; p less than 0.005).

Association of rheumatoid factors in renal transplant recipients with cytomegalovirus infection and not with rejection

Because rheumatoid factors (RF) were detected in the circulation of the majority of early renal transplant recipients and could he eluted from rejected transplants, RF were hypothesized to he related to antibody responses to the histoincompatible graft, The possibility that EF production might have been related to infection and not rejection has not been considered previously. Therefore, we investigated serial serum samples from 147 adult renal transplant recipients for RF with latex agglutination and radioimmune assays. RF were detected hi the sera of 32 patients, 30 of whom had coincident active cytomegalovirus (CMV) infections. Another 45 patients with active CMV infections did not have detectable circulating RF. In contrast, of 74 patients who experienced a total of 103 treated reversible or irreversible rejection episodes in the absence of evidence of active CMV infections, only 2 patients produced RF during their rejection episodes. Nine of the patients who did not produce RF during a rejection episode subsequently produced RF during a later CMV infection. These data indicate that EF production in renal transplant recipiento is associated with CMV infection and not rejection. Moreover, EF production was found to be more frequently associated with primary and severe CMV infections than with secondary or milder CMV infections. SF production was not more frequent in patients who were HLA-DR-4-positive., older, or female, characteristics that have been associated with RF production in other populations. Ail of the sera, with detectable RF contained IgM antibodies that were directed to the Fc portion of human IgG, and about half contained additional IgM antibodies directed to Fab. Thus CMV infections may be the stimuli for the IgM anti-Fab antibodies that have been reported in pretransplant serum samples. Eleven patients produced IgG or IgA RF in addition to IgM RF during CMV infections.

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.

Two alloantigens on human monocytes: A diallelic system?

A positive monocyte crossmatch and therefore anti-monocyte antibodies are negative factors in bone marrow and renal transplantation. When the monocyte antigens themselves can be recognized, matching for the antigens involved here may become a possibility. In order to find useful anti-monocyte sera as typing reagents, human sera were screened against panel cells. Several monocyte specific sera were obtained. These sera recognized two monocyte antigens, HMA-1 and HMA-2. No similarity with any of the HLA antigens was observed. Every individual tested was positive for at least one of these two monocyte antigens, suggesting that HMA-1 and HMA-2 constitute a diallelic system.

Immunopathological abnormalities in the normal skin of patients with rheumatoid arthritis in relation to clinical and serological findings: a one year follow up study.

Fifty two patients with seropositive rheumatoid arthritis (RA) were studied over a period of one year to investigate possible relationships among changes of circulating immune complexes (CIC), deposits of immunoglobulins and complement around the cutaneous blood vessels, clinical activity of the disease, and the presence of extra-articular manifestations (EAM). The presence or absence of IgM and C3 in and around the cutaneous blood vessels correlated significantly with the presence or absence of extra-articular features in cross sectional and longitudinal studies. Patients with evidence of these cutaneous immune deposits also had a greater prevalence of CIC as determined by the Clq binding assay (ClqBA) or polyethylene glycol (PEG) assay for IC containing IgM (IgM IC). Although the degree of perivascular mononuclear cell infiltration around the blood vessels in the papillary dermis was related to the patients clinical state at the initial assessment, it did not correlate with the later changes in the activity of the joint disease or the occurrence of EAM. Thus the deposition of immunoglobulin or complement, or both, seems to be independent of cellular infiltration. The meaning of these cellular infiltrates is not yet fully understood. Our study has shown that many patients with RA who appeared to have only joint disease in fact had subclinical systemic disease as reflected by a positive skin biopsy or CIC. Moreover, the disappearance of IgM deposits from the skin correlated with the disappearance of EAM and improvement of joint disease.

Definition of Two Monocyte-Specific Antigens, One of Which Correlates with the 9 a Antigen

Anti-monocyte antibodies are negative factors in bone marrow and renal transplantation [1]. If the monocyte antigens themselves can be recognized, typing and perhaps matching for these antigens will be possible, which may further improve the results of transplantation.

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 dys? function; and nine had renal dysfunction plus respira? tory or haematological abnormalities. Two patients were regarded as a separate group because their in? fections occurred two to four weeks after graft neph rectomy. 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 pre? dominantly 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 lym? phocytes at 22?C and were precipitated by 3-5% macrogol, suggesting that they were circulating as immune com? plexes. 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.