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Biomedical subjects

M Fotino

Publications and source records attributed to M Fotino.

At least 73 records · Page 4Linked to original sources

Association of HLA-DRw2 with autoimmune thrombocytopenic purpura.

Peripheral blood lymphocytes from 38 patients with autoimmune thrombocytopenic purpura (AITP) were tested for HLA-A, -B, and -C alloantigens. Isolated B lymphocytes from 20 of these patients were tested for HLA-DRw (Ia) alloantigens. The profile of HLA alloantigens in the patients with AITP was significantly different from that of a matched control population. The most significant finding was the presence of the HLA-DRw2 alloantigen in 75% of patients as compared with 23% in the control population, P less than 0.001, relative risk 10.0 (A relative risk of 1 would indicate no association between the presence of the antigen and the disease.) The co-occurrence of either A3 and B7 (known to be in linkage disequilibrium with DRw2) or A26 and Bw38 was significantly increased as compared with the control population (P less than 0.001). Of the patients positive for DRw2, 47% had the association A26 and Bw38 as compared with the control population association incidence of 21% (P less than 0.1). Thus, in the patient population, A26-Bw38 appears to be a haplotype that is in linkage disequilibrium with DRw2 (as presumably is the case with A3-B7). These data indicate that a predisposition to AITP is inherited with a DRw2 gene of the major histocompatibility system.

Autoimmune Diseases↗

Adverse presensitization to renal transplants. Detection by utilization of a D locus antigen-defined lymphoblastoid cell panel as targets in antibody-dependent cell-mediated cytotoxicity assays.

Sera obtained before transplantation from 52 consecutive renal allograft recipients were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) and for complement-dependent cytotoxic antibodies (CDC). A D locus antigen-defined lymphoblastoid cell panel (B lymphoblastoid cell panel) was used as targets for the ADCC, and a peripheral blood lymphocyte (PBL) panel from 40 donors was used as targets for the CDC. Of the 343 ADCC assays, 118 of 168 performed with pretransplant sera from 24 recipients with early graft loss were positive, whereas only 81 of 175 performed with pretransplant sera from 25 recipients with a successful graft outcome were positive (P less than 0.001). A significantly greater degree of presensitization to the B lymphoblastoid cell panel was found in the group that lost their grafts as compared to the group with successful grafts (69% versus 49%, P less than 0.001). Sera from all six recipients with hyperacute rejection were positive in the ADCC before and after absorption with pooled platelets. In contrast, pretransplant CDC results were not predictive of ultimate graft outcome. Utilizing any level of cytotoxicity against the PBL panel as an index of adverse presensitization, no significant correlation between pretransplant CDC results and graft outcome was observed. These results suggest a prognostic role for ADCC using a B lymphoblastoid cell panel as targets to screen and identify high-risk potential graft recipients.

Antibody-Dependent Cell Cytotoxicity↗

Human gamma globulin enhances the survival of renal allografts.

Ninety seven transplant recipients participated in a controlled, clinical trial measuring the graft-enhancing property of a human gamma globulin preparation. The latter was prepared from the blood of pregnant women (RPGG) and contained antibodies with specificities for HLA locus products. Data analysis indicated that RPGG treated recipients had enhanced survival rates of their grafts if they had received one or more blood transfusions prior to transplantation.

Antilymphocyte Serum↗

Disease associations of the Ia-like human alloantigens. Contrasting patterns in rheumatoid arthritis and systemic lupus erythematosus.

Increasing evidence has been obtained of the special value of Ia-like B-cell alloantisera for demonstrating disease associations with histocompatibility antigens. This was particularly evident for the study of the immunogenetics of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), two conditions frequently considered related. The profiles of antigens recognized by the alloantisera in patients from each disease group was distinctive. Two types of alloantisera were obtained that illustrated the divergence between the twod iseases. One type showed a higher than normal incidence in RA but lower than normal in SLE; the other showed a higher incidence in SLE. While these sera were not totally defined, evidence was obtained that the SLE-reactive alloantiserum related to two alleles of the major histocompatibility complex DRw2 and DRw3, while the RA-reactive alloantiserum related to a common specificity shared by cells positive for either DRw4, DRw7, or DRw10. The data indicate that immunogenetic factors are relevant to the development of both RA and SLE, but that these are distinct for each disease.

Antigens, Surface↗

Lack of association of histocompatibility antigens with primary open-angle glaucoma.

Eighty-seven patients (35 with primary open-angle glaucoma, 20 with angle-closure glaucoma, and 32 controls) underwent HLA typing of peripheral lymphocytes. Sixteen specificities were detected at the A locus, 19 at the B locus, and four at the C locus. No significant differences were found between patients with either type of glaucoma and control patients.

Ethnicity↗

Contrasting patterns of newer histocompatibility determinants in patients with rheumatoid arthritis and systemic lupus erythematosus.

The Ia alloantigens as measures of different alleles of loci in the major histocompatibility complex were determined in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). The Ia specificities of reagents used were defined by their pattern of reaction with lymphoblastoid lines derived from normal donors homozygous for HLA-D determinants. The reagent specificities included those associated with a single Dw type as well as those reacting with a single specificity shared by several Dw types. Patients with RA had a marked elevation in the frequency of alloantigens detected by reagent sera that recognize various determinants shared by cell lines from HLA-Dw4, Dw7, or Dw10 individuals (Ia 4-7-10). The frequency of mixed lymphocyte culture alleles Dw4 and Dw10 was found to be increased; however this elevation did not approach the higher frequency for the serologically determined antigens of the Ia 4-7-10 group. In contrast, patients with SLE had an increased frequency of reactions with the reagent alloantisera defined by reactions with either HLA-Dw2 or Dw3 positive cell lines. The data suggest that immunogenetic factors are relevant to both groups of patients, but that these are entirely distinct for each disease.

Arthritis, Rheumatoid↗

Renal transplantation between HLA identical siblings. Comparison with transplants from HLA semi-identical related donors.

We compared 26 HLA-A, B identical sibling kidney-transplant recipients followed for one to 10 years, with 104 HLA-A, B semi-identical kidney recipients from living, related donors to determine clinical differences. Graft-survival rates were significantly better in the HLA identical group at two years (85 per cent identical versus 53 per cent in semi-identical, P less than 0.005); patient-survival rates were high for both (96 per cent in identical and 87 per cent in semi-identical at two years, P less than 0.005). The incidence of complications was similar in HLA identical and semi-identical recipients. Nine of the 26 grafts in HLA identical recipients failed one week to eight years after transplantation. Rejection caused most of the graft failures. Recipients of HLA identical-sibling kidney transplants have a high patient and graft survival, but they also encounter many complications. Immunologic rejection occurs, even with negative mixed lymphocyte culture, suggesting the importance of donor determinants other than the HLAA, B and D other than the HLA-A, B and D.

Acute Disease↗

The HLA system in the families of patients with juvenile diabetes mellitus.

The HLA and Bf genotypes were determined in 10 families with one or more children with JDM. A statistically significant association was found between HLA-D-identity and the chance to present JDM within a sibship. No such association was detectable with the SD antigens. A highly significant increase in the frequency of intra-HLA recombination was also found in these families.

Diabetes Mellitus, Type 1↗

Histocompatibility (HL-A) antigens and primary open-angle glaucoma.

To assess the association between open-angle glaucoma and HL-A antigens, the frequencies of 25 HL-A antigens were determined in 49 patients with OAG, and 22 patients with increased intraocular pressure, due to causes other than OAG, using the microcytotoxicity method. The results were compared to 250 individuals from the general population who were tested in the same laboratory at the same period of time. Using rigid statistical analysis, the incidence of the Bw35 antigen was found to be significantly (less than 0.012) higher among OAG patients. In a group of 27 first relatives of OAG patients who were tested at the same time, the frequency of Bw35 antigen was increased compared to the general population. The biological importance of the association between Bw35 and OAG, which may still be a chance deviation, is not yet fully understood. It may indicate that the Bw35 antigen or the HLA loci are among the genetic factors which produce susceptibility to open-angle glaucoma.

Aged↗

Mixed lymphocyte culture determinants and C2 deficiency: LD-7a associated with C2 deficiency in four families.

Four families with C2 deficiency were studied. Among eight HL-A haplotypes involved with C2 deficiency, five were HL-A 10,W18. Three homozygotes for C2 deficiency from different families were mutually nonreactive in mixed lymphocyte cultures (MLC) and the heterozygotes from the fourth family failed to react to the homozygous cells. It appeared that identical MLC determinants were associated with all the genes from the different families that related to C2 deficiency. Further experiments identified the MLC determinant, LD-7a, as being involved. These results suggest marked linkage disequilibrium between the genes for C2 deficiency and the major histocompatibility complex (MHC). Studies of possible recombinants have offered tentative evidence for the positioning of the locus for C2 deficiency with respect to other segments of the MHC.

Chromosome Mapping↗