Biomedical subjects

Juan C Scornik

Publications and source records attributed to Juan C Scornik.

7 recordsLinked to original sources

PubMed2006

Measuring human complement activation by HLA antibodies.

CONTEXT: The clinical significance of HLA antibodies in transplantation depends on their ability to activate complement, which is measured by the standard complement-dependent cytotoxicity test. Recent reports indicate that C3b measurement on target cells may be a better indicator of human complement activation than standard cytotoxicity. OBJECTIVE: To determine the characteristics of the test, the role of other complement components, and the potential influence of the patient's own complement activity. DESIGN: The T-cell deposition of multiple complement components triggered by HLA alloantibodies was evaluated by flow cytometry using normal human serum as the source of complement. Complement activity in patients' sera was measured after activation with a standard antibody. RESULTS: When HLA antibodies activate complement, C3b deposition is usually highest, followed by that of C4b and C5b. Deposition of C1q, C3d, iC3b, or C5b-9 was low or undetectable in this study. The C5 was activated only when relatively high levels of C3b were present. There was a critical concentration of antibody, unique for each patient, below which activation of C3 declined abruptly. The complement activity in the serum of candidates for liver, heart, and lung transplantation that was tested with a standard antibody was similar to normal serum. In contrast, kidney transplant candidates exhibited higher complement activity. Unexpectedly, serum C3 activity was retained for at least 72 hours after collection. CONCLUSIONS: Measurement of C3b, and in some instances C4b or C5b, offers a better definition of the ability of HLA antibodies to activate human complement than tests that are in current use. The results provide a necessary baseline to conduct clinical correlation studies.

Complement Activation↗

PubMed2005

IVIG and HLA antibodies. Evidence for inhibition of complement activation but not for anti-idiotypic activity.

The immediate effects of IVIG can be due to the presence of anti-idiotypic antibodies or inhibition of complement, but there is limited data about these possible mechanisms specifically on HLA antibodies (HLA Abs). Potential blocking activity of IVIG on HLA Ab binding and complement activation was investigated by flow cytometry. IVIG did not inhibit the IgG binding of any of 23 sera from sensitized patients containing Abs to several different HLA specificities. In contrast, IVIG produced significant dose-dependent complement inhibition. Low IVIG concentrations could be inhibitory if there was little C3 activation, but high concentrations were needed when C3 was activated more efficiently. The data do not support any significant contribution of anti-idiotypic antibodies against HLA Abs to the activity of IVIG. The results also highlight a relationship between the magnitude of C activation and the C inhibitory effect of IVIG.

Antibodies, Anti-Idiotypic↗

PubMed2004

Human leukocyte antigen antibodies and human complement activation: role of IgG subclass, specificity, and cytotoxic potential.

BACKGROUND: Human leukocyte antigen (HLA) antibodies are defined as complement (C) fixing and clinically relevant based upon the complement-dependent cytotoxicity (CDC) test. However, the sub-lytic activation of individual C components is of critical biologic significance. The requirements of HLA antibodies to activate human C are not known. METHODS: IgG, IgM, IgG subclasses, and human C3b deposition upon T cells were evaluated by flow cytometry with sera from HLA-sensitized patients and human monoclonal HLA antibodies. RESULTS: Comparative studies showed that there was poor correlation between the amount of IgG on target cells and their ability to produce CDC. Human C3b deposition was influenced more by the particular serum/cell combination under study than by the amount of IgG, with some combinations showing high IgG and low C3b and others showing low IgG and high C3b. IgG1 was the predominant IgG subclass in all patients. The other subclasses were low or undetectable and did not correlate with C3b deposition. Human monoclonal HLA antibodies, mostly IgG1, did not activate human C efficiently despite high IgG binding. However, combinations of two monoclonal antibodies to different epitopes of the same antigen did produce significant C3b deposition. CONCLUSIONS: Contrary to common assumptions, CDC, IgG binding, and IgG subclass are poor predictors of human C activation by HLA antibodies. The mix of specificities in a given serum and the antigens of a particular target cell appear to determine the efficiency of C activation. Measuring both antibody and C3b deposition (or other C component) may improve the assessment of donor-recipient compatibility.

Antibodies, Monoclonal↗

PubMed2002

The changing causes of graft loss and death after kidney transplantation.

BACKGROUND: The results of kidney transplantation have improved markedly over the last three decades. Despite this, patients still lose grafts and die. We sought to determine whether the causes of graft loss and death have changed over the last 30 years. METHODS: We reviewed patients who underwent transplantation or who died between January 1, 1970 and December 31, 1999. We compared the causes of graft loss or death for three decades: 1970 to 1979, 1980 to 1989, and 1990 to 1999. RESULTS: From January 1, 1970 to December 31, 1999, we performed 2501 kidney transplantations in 2225 patients. For the three periods, 210, 588, and 383 patients lost their grafts, respectively. Graft survival increased substantially. Graft loss occurred later after transplantation, with 36.0% losing grafts in the first year during 1970 to 1970, 22.8% during 1980 to 1989, and 11.4% during 1990 to 1999. Death with a functioning graft increased from 23.8% for 1970 to 1979 to 37.5% for 1990 to 1999. Concomitantly, rejection as a cause of graft loss fell from 65.7% for 1970 to 1979 to 44.6% for 1990 to 1999. Approximately two thirds of the patients who died after transplantation died with a functioning graft and one third died after returning to dialysis. Cardiac disease as a cause of death increased from 9.6% for 1970 to 1979 to 30.3% for 1990 to 1999. Deaths from cancer and stroke also increased significantly over the three decades from 1.2% and 2.4%, respectively, for 1970 to 1979, to 13.2% and 8.0%, respectively, for 1990 to 1999. CONCLUSIONS: The causes of graft loss and death have changed over the last three decades. By better addressing the main causes of death, cardiac disease, and stroke with better prevention, graft loss due to death with a functioning graft will be reduced.

Adolescent↗

PubMed2002

Improved flow cytometric detection of donor-specific HLA class II antibodies by heat inactivation.

Flow cytometry is a powerful technique for T-cell crossmatching but is prone to false-positive reactions with B cells. In this study the flow cytometry crossmatch (FCXM) was performed in 319 cases, using the patient's serum untreated and incubated at 56 degrees C for 30 minutes. Heat treatment inhibited B-cell reactivity in 30 of 39 cases. Flow cytometry testing with latex beads coated with human leukocyte antigen (HLA) class II antigens showed no class II antibodies in sera that were completely inhibited by heat treatment. There was no inhibition of class I antibodies to either T or B cells, or of class II antibodies to B cells. Experiments with aggregated IgG showed that inhibition by heat treatment is likely due to the prevention of complement binding to aggregates or dissociation of aggregates, or both. We conclude that heat inactivation is a simple step that eliminates false-positive reactions in the B-cell flow cytometry crossmatch.

B-Lymphocytes↗

PubMed2002

Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report.

Humoral or antibody-mediated rejection in cardiac transplant recipients is mediated by donor-specific cytotoxic antibodies and is histologically defined by linear deposits of immunoglobulin and complement in the myocardial capillaries. Antibody-mediated rejection often is accompanied by hemodynamic compromise and is associated with reduced long-term graft survival. Standard immunosuppression, designed to target T cell immune function, is largely ineffective against this B cell-driven process. Current treatment options for humoral rejection are limited by a lack of specific anti-B cell therapies. We present the case of a 50-year-old woman with hemodynamically significant humoral rejection resistant to steroids, cyclophos-phamide, and plasmapheresis who responded to the addition of anti-CD20 monoclonal antibody therapy (rituximab). One year posttransplant, the patient is rejection-free, with normal left ventricular systolic function and coronary arteries.

Acute Disease↗

PubMed2002

Obesity does not portend a bad outcome for kidney transplant recipients.

BACKGROUND: Kidney transplant programs may avoid transplantation in obese patients because of reports indicating that obese patients have poorer outcomes than do nonobese patients. We recently reviewed our experience. METHODS: Patients receiving a kidney transplant between January 1, 1990 and December 31, 1999 were divided according to body mass index (BMI): group 1, BMI<25 (n=457); group 2, BMI> or =25 and <30 (n=278); and group 3, BMI> or =35 (n=98). RESULTS: Cadaveric graft survival rates at 2 years were 85% for group 1, 88% for group 2, and 85% for group 3 (P>0.10). Cadaveric patient survival rates at 2 years were 92% for group 1, 91% for group 2, and 94% for group 3 (P>0.10). There were no differences in technical losses or in posttransplantation wound complications. Group 3 patients, however, did have a higher incidence of steroid-induced posttransplantation diabetes mellitus than the other two groups (P<0.01). CONCLUSION: Obese transplant recipients have similar outcomes to nonobese patients.

Adult↗