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Biomedical subjects

E M Mickelson

Publications and source records attributed to E M Mickelson.

At least 55 records · Page 3Linked to original sources
PubMed1984

Change in functional phenotype of cloned human alloreactive cytolytic T cells.

Alloreactive T cell clones primed in vivo were tested for the expression of T cell differentiation antigens CD2, CD3, CD4, and CD8. Each of 29 different clones were found to express CD2 and CD3, but were variable in their expression of CD4 (7 positive clones) and CD8 (15 positive clones). Six clones were positive for both CD4 and CD8. One of the 29 clones expressed neither CD4 or CD8. Over a period of 12-18 weeks of culture, these clones began to lose their alloreactivity but acquired NK-like activity. By changing the concentration of TCGF, the "allo" and "NK-like" lytic activities could be modulated. After 18 weeks of culture, these clones lost their alloreactive specificity, but not their NK activity. The expression of surface markers was unchanged. CD2 and CD3 molecules were determined to play a role in both the alloreactive and NK activity of these clones.

Adult↗
PubMed1984

Ninth International Histocompatibility pre-workshop testing of Dw6 HTCs. Two subtypes of Dw6.

In the scope of the cellular part of the 9th International Histocompatibility Workshop, the offered homozygous typing cells (HTCs) of several specificities have been screened in a pre-Workshop. In Leiden and Seattle all HTCs typing for "HLA-Dw6" have been tested. This implied that in both laboratories mixed lymphocyte culture (MLC) matrices were performed between the Dw6 HTCs and that all HTCs were tested as stimulator cells against a panel of heterozygous responder cells. The results clearly demonstrated that "HLA-Dw6" as defined by the different participating laboratories can be split into two major groups, Dw6.a and Dw6.b. This observation confirms and extends previous reports. None of the 9th Workshop B-cell sera could discriminate between the two presently described subgroups of HLA-Dw6.

HLA-DR Antigens↗
PubMed1983

Analysis of the HLA-DRw8 haplotype: recognition by HTC typing of three distinct antigen complexes in Caucasians, Native Americans, and Orientals.

We have used seven HLA-D homozygous typing cells (HTC) in a comparative study of the DRw8 antigen complex in three racial groups. Three distinct HLA-D specificities were recognized, each associated with HLA-DRw8. Four of the HTC defined a DRw8-associated HLA-D specificity designated 8.1, one defined a specificity designated 8.2, and two defined a specificity designated 8.3. Each of the three specificities showed an association with a distinct racial group: Dw"8.1" in Caucasians, Dw"8.2" in Pacific Northwest Indians, and Dw"8.3" in Orientals. An informative primed lymphocyte (PLT) cell generated against a Dw"8.1" haplotype was able to distinguish 8.1 from 8.2 and 8.3. Using selected anti-DRw8 sera, a serologic distinction between 8.1 and 8.3 could also be made. It was thus possible, by using both cellular and serologic techniques in a comparative population study, to recognize at least three HLA-D-defined splits of the DRw8 haplotype.

Asian People↗
PubMed1982

HLA antigens in Yakima Indians with rheumatoid arthritis. Lack of association with HLA-Dw4 and HLA-DR4.

Women of the Yakima Indian Nation, a northwest Native American population, are known to have an increased prevalence of a rheumatoid arthritis-like disease characterized by erosive arthritis, frequent involvement of metacarpophalangeal and wrist joints, and positive rheumatoid factor. These patients are frequently positive for antinuclear antibodies and often demonstrate adverse reactions to gold therapy. HLA antigens were determined for 29 Yakima Indians with this disease, but there was no increased frequency of either HLA-Dw4 or HLA-DR4, in contrast to other populations with rheumatoid arthritis. There was, however, a trend toward an increase in HLA-B40 and a decrease in HLA-DR8. The relative risk for rheumatoid arthritis in Yakima Indians was 2.53 in the presence of B40 and 0.28 in the presence of DR8.

Arthritis, Rheumatoid↗
PubMed1982

Definition of LD "4 X 7": a unique HLA-D specificity defined by two homozygous typing cells.

Two homozygous typing cells (HTC) from the Eighth International Histocompatibility Workshop were used to define a unique HLA-D specificity, designated LD "4 X 7". Typing cell 8W316 (Seattle) was obtained from a donor of Japanese descent; cell 8W324 (Leiden) was obtained from a European Caucasian donor. The HLA-D specificities defined by these two HTC showed a significant correlation (R = 0.65) in unselected panel studies and clear segregation as a single determinant within families. LD "4 X 7" was found in low frequency in Caucasians (1.0%) but with detected with a frequency of 24% in Japanese. The cells of the donors of HTC 8W316 and 8W324 express DRw9, and the LD "4 X 7" antigen fills an HLA-D locus "blank" on DRw9-positive haplotypes. The frequency of LD "4 X 7" noted in this study corresponds to the frequency of DRw9 reported for Japanese and Caucasian ethnic groups, a further indication that LD "4 X 7" and DRw9 are associated.

Epitopes↗
PubMed1981

Marrow transplantation from donors other than HLA identical siblings.

As of 31 December 1979, 39 patients in Seattle have received marrow grafts from donors other than HLA genotypically identical siblings. Sixteen transplants were between siblings, 21 from a parent to a child, one from a paternal uncle, and one from an unrelated donor. Ten patients had aplastic anemia and 29 had a hematological malignancy. As of 1 February 1980, only one of the ten patients transplanted for aplastic anemia is currently alive (greater than 1048 days) with a normal marrow and without graft-versus-host disease. This surviving patient was untransfused and received marrow from an HLA phenotypically identical mother. There were five episodes of graft rejection among the ten aplastic patients. Among the 29 patients transplanted for hematological malignancy, 12 (42%) are surviving from greater than 64 to greater than 995 days. Twelve of 29 patients were transplanted while in remission and eight (75%) are alive from greater than 148 to greater than 790 days. The two most frequent causes of death were relapse of leukemia and interstitial pneumonia. Only two patients died from complications clearly related to graft-versus-host disease. Five of the surviving patients were phenotypically identical with their donor for HLA, while seven were incompatible for some HLA determinants. One patient--donor pair was incompatible for HLA-D and DR as a result of HLA-B/D recombination, and six pairs were incompatible for HLA-A and/or B.

Anemia, Aplastic↗
PubMed1981

Studies of the response in mixed leukocyte culture of cells from patients with aplastic anemia to cells from HLA-identical siblings.

We have studied the mixed leukocyte culture (MLC) reactions of 64 patients with severe aplastic anemia. Their peripheral blood mononuclear cells showed an increased relative response (RR) to cells from HLA-identical siblings as compared to cells from normal HLA-identical siblings, confirming the results reported in an earlier series of 34 patients. Elevated RRs were associated with patient antidonor lymphocyte antibodies as detected by the antibody-dependent cell-mediated cytotoxicity assay, but were not associated with antidonor complement-dependent cytotoxic antibodies or with antidonor cytotoxic T lymphocytes. Among 98 patients receiving marrow grafts from HLA-identical sibling donors, those with elevated RRs before transplantation were more apt to reject the transplant than those without (P less than 0.0001). There was no elevation of the RR in 10 untransfused patients, although positive RRs were noted in 2 patients within 12 to 24 hr of their first transfusions. Five patients with identical twins were also tested, and elevated RRs were noted in three. Although blood transfusion appears to be responsible for the increased RRs observed in some aplastic patients, genetic differences between donor and recipient were not always necessary for eliciting an increased MLC response, suggesting that mechanisms other than alloimmunization are involved.

Adolescent↗
PubMed1980

Two homozygous typing cells defining a subgroup of HLA-Dw6.

Homozygous typing cells (HTC) and responder cells from a panel of randomly selected unrelated caucasians were used in a study of the HLA-Dw6 antigen complex. Using HTC characterized by the Eighth International Histocompatibility Workshop, the Dw6 specificity was shown to be a broadly defined, heterogeneous cluster that could be subdivided. An HTC from our laboratory, 8W146, and a second locally identified cell, EMJ, were used to define one clearly distinguishable subcluster of Dw6, provisionally termed "6.1." HTC 8W146 and EMJ were mutually nonreactive in mixed leukocyte culture and showed strong association (r = 0.85) when used as stimulators against the caucasian cell panel. The calculated gene frequency of the 8W146/EMJ determinant in this population was 0.024. In an informative family, the 6.1 specificity could be shown to segregate independently of other Dw6 subgroups. DR typing of 8W146 and EMJ showed both to be positive for MT-1 and MT-2 but negative for DRw "3 + 6."

Epitopes↗
PubMed1980

Autoimmune and alloimmune phenomena in patients with aplastic anemia: cytotoxicity against autologous lymphocytes and lymphocytes from HLA identical siblings.

We have studied peripheral blood lymphocytes of 117 patients with severe aplastic anemia and 237 healthy individuals for reactivity against autologous lymphocytes and/or lymphocytes from HLA-identical siblings using a 51Cr release assay. Lymphocytes from 29% of the patients exhibited reactivity against their own lymphocytes, while only 3% of lymphocytes from normal individuals showed such reactivity. Lymphocytes from 49% of the patients showed reactivity against lymphocytes from their HLA-identical siblings compared to 4% of normal individuals. Correlation existed between allogeneic and autologous reactivities (p < 0.001), suggesting a common pathway for cytotoxicity. Both reactivities showed an association with extremely low granulocyte counts (p < 0.01) and an inability of the patient's mononulcear cells to stimulate in allogeneic mixed leukocyte culture (p < 0.05) as well as an inverse correlation with time from diagnosis (p < 0.001). At least two explanations exist for the transfusion-independent autologous and allogeneic cytotoxicities: (1) they could be epiphenomena secondary to the stem cell defect, such as the loss of a cell that suppresses (or regulates) naturally occurring cytotoxic cells, or (2) they may be involved in the cause of the disease.

Anemia, Aplastic↗
PubMed1979

Association of interstitial pneumonia and diminished in vitro lymphocyte blastogenesis in human marrow graft recipients.

The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days after marrow grafting by stimulation with lymphocytes from unrelated individuals or phytohemagglutinin (PHA). Fourteen of the 51 patients subsequently developed interstitial pneumonia (IP). The relative responses of the lymphocytes of patients who developed IP were significantly lower than those of individuals not developing IP (P less than 0.01 for allogeneic cells, P = 0.02 for PHA). These nonspecific in vitro tests of cell-mediated immunity are of value in identifying patients at risk of developing IP.

Anemia, Aplastic↗
PubMed1976

Correlation of the relative response index with marrow graft rejection in patients with aplastic anemia.

Thirty-four patients with severe aplastic anemia were treated with cyclophosphamide or total body irradiation and an infusion of marrow from a genotypically HLA-identical sibling donor. Engraftment occurred in all patients but rejection was noted in 12. Mixed leukocyte culture (MLC) tests undertaken before grafting to determine donor-recipient histocompatibility were analyzed retrospectively. The response of patient cells to sibling cells in mixed culture was compared to the response of patient cells to cells of an unrelated individual and expressed as a relative response index (RRI). Of the 12 patients who showed positive RRI to donor leukocytes in pregraft MLCs, 9 rejected their grafts, wheras of 23 patients with negative RRI only three rejected their grafts (P LESS THAN 0.005). The results suggest that the MLC test can detect individuals who are most likely to reject their HLA identical sibling graft.

Adolescent↗
PubMed1976

Aplastic anemia: failure of patient leukocytes to stimulate allogeneic cells in mixed leukocyte culture.

One-way mixed leukocyte cultures were used to study the ability of cells from 53 patients with aplastic anemia and 65 of their HLA-identical siblings to stimulate and to respond to cells from unrelated individuals. The capacity of leukocytes from 28 of 53 patients to stimulate was diminished or absent, wheras their ability to respond remained comparable to that of cells from their HLA-identical siblings. Leukocytes from the group of patients with the lowest peripheral lymphocyte count were least stimulatory. The results indicate that in acquired aplastic anemia there exists a dissociation between stimulation and response in mixed culture.

Anemia, Aplastic↗