Biomedical subjects

Marilyn Marrari

Publications and source records attributed to Marilyn Marrari.

3 recordsLinked to original sources

PubMed2005

Serum analysis after transplant nephrectomy reveals restricted antibody specificity patterns against structurally defined HLA class I mismatches.

This study deals with HLA-mismatched kidney transplants that have been removed following rejection. Sera from 27 patients were screened for HLA-specific antibodies by direct complement-dependent lymphocytotoxicity with HLA-typed cell panels. Circulating donor-specific antibodies were detected in 3 cases (11%) before and in 26 cases (97%) after allograft nephrectomy. These findings demonstrate the production of donor-specific antibodies in patients with rejected transplants, but in most cases, they were undetectable before nephrectomy, because the graft had adsorbed them. With an HLAMatchmaker-based serum analysis program, we observed restricted antibody specificity patterns against amino acid triplet-defined epitopes on donor HLA-A,B antigens. Many donor triplets were non-reactive while others were apparently recognized by antibodies. In some patients, the donor triplet specific antibodies persisted for a long time whereas in many other patients, they became undetectable after a few months. The characterization of the antibody specificity profiles of post-allograft nephrectomy sera is clinically useful in defining criteria of HLA mismatch acceptability for sensitized patients awaiting another transplant. It provides also opportunities for determining the relative immunogenicity of mismatched triplets.

Adult↗

PubMed2003

Multilaboratory evaluation of serum analysis for HLA antibody and crossmatch reactivity by lymphocytotoxicity methods.

CONTEXT: This report presents results of the serum antibody analysis and crossmatch challenges in the proficiency testing program for histocompatibility testing jointly sponsored by the American Society for Histocompatibility and Immunogenetics and the College of American Pathologists. OBJECTIVE: To obtain information about consensus rates among participating laboratories that reported antibody screening and crossmatch results by direct complement-dependent lymphocytotoxicity (CDC) and/or anti-human globulin (AHG)-augmentation methods. DESIGN: We analyzed responses from approximately 165 laboratories participating in 32 surveys during 1993-2000. Most of the testing was done by CDC methods, but increasing proportions of laboratories are using AHG augmentation of these techniques; almost one half of the serum screenings and crossmatches were done by AHG. RESULTS: A total of 40 serum specimens were screened to determine the percent panel-reactive antibody (PRA) and identify HLA-specific antibodies. Participants often reported very wide ranges of PRA values. Panel-reactive antibody ranges exceeded 60 percentage points for 16 (40%) of the serum screening results by CDC and for 31 (77%) of the results by AHG. The interlaboratory variability of PRA values suggests that in many laboratories, the CDC or AHG procedures were often too insensitive or overly sensitive. The antibody identification results revealed inconsistent patterns among the participants performing CDC or AHG screening. Most participants reported the same primary antibody specificities by both methods. The consensus levels were generally high for the monospecific sera. On the other hand, there was much less agreement among the participants if the sera reacted with 2 or more HLA antigens. Participants using the more sensitive AHG method reported additional antibody specificities in many specimens, but invariably the consensus levels were rather low. A total of 192 serum-cell combinations were used for the crossmatch challenges. There was considerable interlaboratory variability; 21% of the CDC crossmatches and 36% of AHG crossmatches failed to reach the 90% consensus threshold. CONCLUSIONS: This experience demonstrates considerable inconsistencies in serum screening and crossmatching among laboratories participating in the American Society for Histocompatibility and Immunogenetics/College of American Pathologists surveys. A lack of uniformity in test results may limit the efficient application of these methods in a clinical setting. Standardization of crossmatch and antibody screening techniques is highly desirable.

Antibody Specificity↗

PubMed2002

HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. II. Verification of the algorithm and determination of the relative immunogenicity of amino acid triplet-defined epitopes.

HLAMatchmaker is a computer algorithm that assesses human leukocyte antigen (HLA) compatibility at the structural level by intralocus and interlocus comparisons of polymorphic amino acid triplets in antibody-accessible sequences of HLA class I molecules. This program permits the identification of mismatched HLA antigens that share all of their polymorphic triplets with the patient's HLA antigens and, therefore, could be considered fully compatible. The validity of this algorithm has been verified by analyzing the antibody specificity patterns of 127 well-characterized sera (panel reactive antibody [PRA] > 80%) that had been screened by direct complement-dependent and/or anti-human globulin augmented lymphocytotoxicity testing with large HLA-typed cell panels. A 2 x 2 table-based Chi-square analysis program was applied to determine positive and negative correlations between serum reactivity and the presence HLA triplets assigned from the HLA types in the cell panel. The results indicate that high PRA patients do not produce antibodies to shared triplets on mismatched HLA antigens. Moreover, this serum analysis has permitted the identification of triplets with different degrees of immunogenicity as indicated by the frequencies of positive and negative correlations of serum reactivity with the HLA-typed cell panel. Mismatching for triplets with low immunogenicity provides further opportunities for identifying donors with acceptable HLA mismatches for highly sensitized patients.

Algorithms↗