HLA-B27 is frequently, but not invariably, found in patients with spondylarthritic diseases. Recently it has been shown that HLA-C-locus antigens w1 and w2 (w1/2) are in linkage disequilibrium with B27. A group of 139 patients with seronegative arthritis or spondylitis has been studied to determine the clinical and radiographic features associated with these antigens. An increased frequency of spondylarthritis was present in HLA-B27-negative, Cw1/2-positive patients when compared with B27- and Cw1/2-negative patients (P less than 0.01). In addition, a large group of patients who did not fulfill accepted criteria for a specific spondylarthritic syndrome were identified; the frequency of both HLA-B27 and Cw1/2 was greater in these individuals than in healthy blood donors. Thus HLA-Cw1/2 are spondylitis-associated antigens. These findings suggest that the critical genetic locus is neither B27 nor Cw1/2 but is a closely linked gene.

Arthritis, Reactive↗

PubMedDate not supplied

HLA alloantibodies and the mechanism of the antiglobulin-augmented lymphocytotoxicity procedure.

HLA Class I alloantigens express multiple epitopes which can be defined serologically using human HLA alloantibodies (aAb). We have shown that the vast majority of HLA antisera exhibit the CYNAP phenomenon (complement-dependent cytotoxicity (CDC) negative, adsorption positive) which can be identified by conversion to direct CDC positive reactivity with the addition of an antihuman immunoglobulin (Ig) light chain (AHG) reagent. In this study, the immunochemical mechanisms responsible for the CYNAP phenomena and how AHG overrides CYNAP have been further characterized using affinity-purified HLA aAb, class-specific anti-IgH reagents and human C1q binding assays quantified by flow cytometry. We have found that CYNAP reactions are not the result of low affinity aAb or generally caused by non-complement fixing HLA aAb. Our experiments illustrate that only anti-human IgL AHG reagents can consistently augment CDC and override CYNAP; anti-IgH have not effective. Two noncompeting HLA aAb of different epitopic specificity or one aAb in conjunction with the AHG-augmenting reagent results in striking synergy with a 200 to 400% increase in binding of C1q. We conclude from these and other experiments detailed in this article that an IgM aAb or either two adjacent, noncompeting IgG HLA aAb bound to spatially distinct epitopes on a single HLA molecule or a monospecific IgG HLA aAb in concert with the AHG binding to this HLA aAb, is required for efficient (bivalent) C1q binding and initiation of C-mediated lympholysis. In contrast, the CYNAP phenomenon usually occurs because monospecific HLA aAb directed against a single epitope cannot effect high affinity, bivalent interaction with Clq and activate complement that would ultimately lead to cytolysis.

Antibodies, Anti-Idiotypic↗

PubMedDate not supplied

Low incidence of red cell and HLA antibody formation by bone marrow transplant patients.

BACKGROUND: Bone marrow transplant (BMT) patients, although immunosuppressed, are at risk for the development of red cell (RBC) and HLA antibodies, and they often are given filtered blood in an effort to prevent the latter complication. This study attempts to determine the rate of formation and the specificity of both RBC and HLA alloantibodies in this patient population. STUDY DESIGN AND METHODS: BMT patients (148 received autologous marrow; 45 received allogeneic marrow) from an 18-month period, including patients with leukemia (57 patients), lymphoma (54), breast cancer (68), myeloma (8), myelodysplastic syndrome (5), and aplastic anemia (1), were studied to determine the rate of alloantibody formation to RBC and HLA antigens. A total of 2,410 RBC antibody screens were performed. The patients received 3,921 packed RBCs and 5,915 single-donor platelet units; all were irradiated and administered via white cell-reduction filters. RESULTS: Seven (3.6%) of 193 patients had RBC antibodies upon hospital admission. Four (2.1%) of 193 developed RBC antibodies during the course of BMT: 3 patients had one RBC antibody and 1 patient had two RBC antibodies. RBC antibodies included anti-E (n = 2), anti-M (n = 1), anti-Jkb (n = 1), and anti-Lu14 (n = 1). Thus, 98 percent of patients (189/193) did not develop new (182/186) or additional (7/7) RBC antibodies during BMT. BMT patients were also screened weekly for HLA antibody formation (60-cell panel). Upon admission, 170 (85%) patients were negative. Of these, 8 (4.7%) developed persistent HLA antibodies (mean panel-reactive antibody score, 33 +/- 29%) and 9 (5.3%) were variably positive. Thus, in our setting and population, RBC antibody formation was 0.1 percent per unit transfused, and the HLA alloimmunization rate was 5 to 10 percent. CONCLUSION: As RBC antibody screens are done every Monday, Wednesday, and Friday on this BMT service and as RBC antibody formation is low in these patients, screening for unexpected antibodies might be possible on a more infrequent basis. Also, the rate of HLA alloimmunization in this population receiving filtered blood components is low.

Adult↗

PubMedDate not supplied

Procurement and identification of HL-A lymphocytotoxic antibodies in sera of nonpregnant, multiparous blood donors.

An efficient procedure for large-scale screening of nonpregnant multiparous blood donor sera is described. Yield of useful HL-A reagents in this population compares favorably to yields obtained from screening pregnant women near term. The advantages of screening nonpregnant donors include stable antibody titers, ease of procurement, and the willingness of voluntary blood donors to return for plasmapheresis.

Blood Donors↗

PubMedDate not supplied

Interactive effect of genes associated with immunoglobulin allotypes and HLA specificities on susceptibility to Haemophilus influenzae disease.

Genes associated with immunoglobulin (Ig) allotype determinants are important in regulation of immune responses to bacterial polysaccharides. Furthermore, loci associated with Ig allotypes have been reported to interact with those associated with the major histocompatibility complex and affect susceptibility to certain diseases. In the present study we determined the frequencies of certain Gm phenotypes in patients with Haemophilus meningitis or epiglottitis and in controls. HLA-A, -B and -DR specificities had previously been determined in the majority of these subjects. Although no Ig phenotype was associated with increased or decreased relative risk of disease, the frequencies of several combinations of HLA specificities and Ig phenotypes were significantly different from those of controls. Thus, for subjects with the Gm phenotype (1, 3, 17; 23; 5, 13, 21), the risk of Haemophilus meningitis or epiglottitis was lower in individuals with HLA-B5 than in those without this specificity (odds ratio less than 0.1, P less than 0.004). In contrast, for subjects with the closely related Gm phenotype differing only by the absence of Gm(23), (1, 3, 17; ; 5, 13, 21), the risk of disease was higher in those with HLA-DR3 than in individuals who lacked DR3 (odds ratio = 11.0, P = 0.02). Although the present data require confirmation in an independent sample, they suggest that complex interactions between genes at two independent loci controlling HLA and Ig allotypes, respectively, may affect susceptibility to Haemophilus disease.

Child↗

PubMedDate not supplied

Characterization of human heart-infiltrating cells after transplantation. V. Suppression of donor-specific allogeneic responses by cloned T-cell lines isolated from heart biopsy specimens of patients after transplantation.

In vitro culture of heart biopsy specimens from patients after transplantation in media containing recombinant human interleukin-2 led to the exudation of host mononuclear-cell infiltrates. Cloned T-cell lines were prepared from such infiltrates and studied for donor-specific mixed lymphocyte reaction and cytotoxic T-lymphocyte activity. Although most T-cell clones (greater than 50%) showed donor-specific reactivity, a small but distinct frequency (2% to 10%) of the cloned T-cell lines did not proliferate against donor or third-party stimulator cells. Of interest was our finding that addition of these non-donor-reactive cloned T-cell lines to autologous peripheral blood mononuclear cells markedly suppressed their donor-specific, but not third-party major histocompatibility complex, unrelated proliferative response and prevented the generation of donor, but not third-party, major histocompatibility complex unrelated cytotoxic T-lymphocyte function. The suppression was not secondary to lysis of donor stimulator cells, lysis of autologous donor-specific CD4+ lymphoblasts, or by selective consumption of interleukin-2. The suppression was mediated at the initiation of sensitization (precursor cell level). These suppressor cells expressed CD3, CD8, CD45RO, and the alpha, beta T-cell receptor, but not CD4 or CD56. These cloned T-cell lines will provide unique reagents to study the molecular basis by which these cells exert their regulatory function.

Antigens, CD↗

PubMedDate not supplied

Characterization of human heart-infiltrating cells after transplantation. VI. Differences in the cytokines produced by individual CD4+ cloned T-cell lines with apparently identical antiidiotype-like reactivity.

Studies of cultures and cloned T-cell lines from mononuclear cell infiltrates in cardiac biopsy specimens have provided a unique resource to study the cellular basis of human organ allograft rejection. Our laboratory has previously shown that biopsy specimens placed on autologous donor MHC-class-II-specific cloned T-cell lines from previous cardiac biopsies led to the isolation of cloned T-cell lines, which appeared to be functionally "antiidiotypic" in nature. Detailed functional analysis of such CD4+ individual antiidiotype-reactive cloned T-cell lines revealed that although some augmented the proliferative response of autologous idiotype-bearing cloned T-cell lines against donor stimulator cells, others markedly suppressed the proliferative response; thus, although each of these antiidiotype-like reactive cloned T-cell lines appears to specifically react with the same idiotype-bearing donor MHC-class-II-specific cloned T-cell line, they were functionally heterogeneous. Analysis of cytokines secreted by these individual clones showed that the antiidiotype-reactive cloned T-cell lines that suppressed the response of idiotype-bearing cells appear to secrete predominantly interferon gamma, whereas those antiidiotype-reactive cloned T-cell lines that augmented the response do not secrete interferon gamma but secrete interleukin-2, -4, and -6. These preliminary data suggest that differences in the predominant cytokines secreted by these individual antiidiotype-reactive cloned T-cell lines may account for their functional differences.

Antibodies, Anti-Idiotypic↗

PubMedDate not supplied

Comprehensive evaluation of heart cases under Workmen's Compensation.

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Disability Evaluation↗