[Analysis of 516 reports of reactions after the transfusion of labile blood products]. / Analyse de 516 rapports de réaction après transfusion de produits sanguins labiles.

BACKGROUND: In order to assess the implemented preventive measures of transfusion reactions (TR) and to make a study of residual reactions, we analyzed 516 TR reports from 14 hospitals, for three years since 1996 to 1998. METHODS: Clinical signs were classified according to seven etiologic categories. Systematic anti-erythrocyte and anti-leucocyte detection, as well as bacterial control of the returned bag were performed. RESULTS: The TR incidence is 3.7 per 1.000 products. Platelet concentrates (PC) provoke 7.4 TR per 1.000 transfusions, and red cell concentrates (RCC) 3.8. There are as many TR with apheresis platelets (AP), pre-storage leuco-depleted, as with random platelets, post-storage leuco-depleted, and as many with leuco-depleted RCC as with non leuco-depleted RCC. Leuco-depleted AP provoke more allergic reactions than other blood components. TR with AP are much more frequent in children than in adults. Plasma removal from AP before transfusion decreases reaction frequency. CONCLUSIONS: The lack in efficacy failure of pre-storage deleucocytation in TR prevention should be due to related patient factors. Etiology of AP allergic reactions deserves further study. PC suspension in synthetic medium before transfusion is an efficient means for RT decreasing. Hemovigilance system has to be improved so that all TR be reported.

[Types of corneal transplantation: experience and review]. / Greffes de cornée typées: expérience et revue.

The authors review the 12 cases of matched corneal transplantation, performed at the CHU of Liège between 1991 and 1997. They expose their results together with a summary of the different hypotheses published so far in the field of corneal graft matching.

[The current status of organ transplantation: the role of xenotransplantation?]. / Etat actuel des transplantations d'organes: place à la xénotransplantation?

In the last few years, transplantation was an area of intense research activity. However, there is a worldwide shortage of donor organs for clinical transplantations. Currently, interest in xenotransplantation research is growing not only because of the increased demand for organs but also because of advances in molecular biology techniques that make possible the genetic or immunological manipulations of the animal donor rather than the human recipient. The better definitions of the mechanisms responsible for xenograft rejection should facilitate appropriate therapeutic strategies for long xenograft survival.

[Kaposi's disease in a female patient with acquired HIV-negative immunodeficiency]. / Maladie de Kaposi chez une patiente souffrant d'une immunodéficience acquise VIH négative.

A 79-year-old woman of Mediterranean ascent suffered from corticosteroid-dependent chronic obstructive lung disease, hypogammaglobulinemia (IgG 1 and 2), decreased CD16 natural killer cell function and non-HIV related CD4 and CD8 lymphopenia. Such immunodeficiency could be either a variant of common variable immunodeficiency or an early stage of the idiopathic CD4 + T lymphocytopenia syndrome. She developed bilateral lesions of Kaposi's sarcoma on the lower extremities resembling the classic European type of the disease. The tumors contained both CD34 + and Factor XIIIa + cells. The HLA-DR5 haplotype was not found. Weekly low intravenous dosages of vinblastine improved the lesions but the patient died from pontic infarction.

HLA-B locus DNA typing: detection of B*7801 and seven additional alleles by BW6-specific exon 2 amplification.

A molecular approach to type a new HLA-B5 antigen, HLA-BSNA, characterized by its unusual association with the public determinant BW6, referred to as B*7801, has been designed. Antigens disclosing serological identity with SNA, BX1 and Te76 were also investigated. Based upon HLA-B exon 2 group-specific PCR, the following procedure was established: 5' and 3' primers were designed by targetting the codons 11-12 (AM) and 81-83 (LRG), respectively, in exon 2 (alpha 1 domain). The 5' primer discriminates with HLA-A, -C genes and pseudogenes, while the 3' primer detects the sequence encoding the BW6 epitope (NLRG) and discriminates it from the BW4 epitope. The combination of this pair of primers specifically amplifies 26 HLA-B alleles. Oligotyping for B*7801 was performed using a combination of two non-radioactively labeled SSO probes identifying positions T45 and D74 in exon 2. To resolve ambiguous hybridization patterns, an additional set of probes was used. The specificity of this BW6-group-specific amplification procedure was investigated on 150 genomic DNA samples. Among them, we obtained 94 amplified DNA products which were tested with eight SSOs. Beside B*7801, the following B alleles could be defined: B*0801, B*35, B*5401, B*5501-2, B*5601-2, B*1501-7 (including B62, B75 and B72) and B*4601. SNA, BX1 and Te76 DNA samples gave similar hybridization pattern providing a clue to the identity of these antigens. This "one PCR and two probes" procedure represents a simple oligotyping strategy which can also be applied to type many other HLA-B specificities.

Molecular characterization of a recombinant HLA-DR1/DR2 haplotype.

Serologic analysis of two families identified an HLA-DR haplotype in which DR1 and DR2 cosegregated. DNA-RFLP analysis of these families with an HLA-DRB probe revealed a pattern of hybridization suggestive of a recombination between DR1 and DR15. Following amplification, cloning, and nucleotide sequencing of HLA-DRB-gene second-exon DNA sequences, three DRB amplification products associated with the novel haplotype were identified: these corresponded to DRB1*0101, DR2 pseudogene, and DRB5*0101. Clones representing the DRB1*1501 and DR1 pseudogenes were not identified: oligonucleotide typing with DRB1*1501-specific probes confirmed the absence of this gene within the DR1/DR2 haplotype. We postulate that the DR1/DR2 haplotype represents a recombinant between those of DR1-Dw1 and DR15-Dw2, and that the crossing-over may have been between the DRB1*0101 gene and the DR2 pseudogene. This is further supported by DNA-RFLP analysis with HLA-DQB and DQA CDNA probes, which revealed conserved linkage genes between the DQB1*0501, DQA1*0101, and DRB1*0101 genes.

Clonally restricted insulin autoantibodies in a cohort of 2200 healthy blood donors.

Serum samples of 2200 blood donors were screened for anti-insulin IgG by enzyme-linked immunosorbent assay. Specificity of detected antibodies was verified by competition with an excess of insulin and observation that saturated anti-insulin IgG were no longer measurable. The upper limit of measured signal in the population was defined as the mean plus three SD. In the direct assay, 32 sera were positive. Among these, 22 (1%) contained saturable insulin antibodies (true positive) and 10 were non-saturable and considered as non-insulin-specific. The positive blood donors were requested to answer a questionnaire and according to their answers, none had ever received insulin, was a first degree relative of a Type 1 (insulin-dependent) diabetic patient or had experienced a hypoglycaemic episode. None of the 22 true positive sera detected by enzyme-immunosorbent assay bound 125-I-insulin to any significant extent. The nine sera yielding the highest signal were further characterized with regard to heavy and light chains as well as species specificity of ligand. Anti-insulin IgG from healthy blood donors contained only one heavy (gamma 1 2/9;gamma 3 7/9) and one light (kappa 8/9); lambda 1/9) chain. Three sera were human insulin specific; two were non-species-specific; the other four bound insulin in the order human = porcine greater than bovine. These results indicate that low affinity clonally restricted antibodies against insulin are present in unselected blood donors with a prevalence of 1%.

The spontaneous ability of normal human IgG to inhibit the Fc receptors of normal human monocytes is related to their binding capacity to lectins.

The lectin-binding capacity of 96 normal human IgG, assessed by solid-phase radioimmunoassay, strikingly varied according to the lectin considered. Indeed, half of the IgG samples exhibited peanut agglutinin (PNA)- and pokeweed mitogen-specific binding capacities superior or equal to 4%, whereas less than 15% of IgG similarly bound to concanavalin A (Con A) and to phytohemagglutinin. The ability of those IgG to inhibit the Fc receptor (Fc-R) function of human monocytes, measured by a classical rosette assay, was inversely correlated to their binding ratios to PNA and Con A only. By affinity chromatography, three groups of IgG were separated: the IgG purified on agarose-PNA columns slightly reduced the Fc-R function (40-45% inhibition); the IgG purified on Sepharose-Con A columns exhibited the highest inhibitory properties (80-85% inhibition); the IgG that did not bind to PNA and Con A columns possessed intermediate inhibitory properties (65-70% inhibition). The different effect of IgG on Fc receptors was conserved when monocytes were first treated by trypsin and was unrelated to their specific binding to human monocytes, to their subclasses, and to their C1q- or protein A-binding capacities. Incubation of monocytes with D-galactose (10 mM) significantly improved their capacity to form IgG rosettes, whereas their incubation with D-mannose (10 mM) significantly reduced the Fc-R function. Scatchard plots of 125I-IgG1 myeloma protein binding to monocytes were linear under basal conditions, as well as after a prior incubation of the cells with D-galactose or D-mannose. Monocytes bound about 16,000 molecules of IgG1 per cell in each instance. In contrast, the mean association constant (Ka) for IgG1 binding was 2.59 +/- 0.50 X 10(8) M-1 under basal conditions, 4.4 +/- 0.75 X 10(8) M-1 after D-galactose incubation, and 1.35 +/- 0.50 X 10(8) M-1 after D-mannose incubation. These data suggest that the level of human monocyte Fc-R function blockade induced by human IgG depends mainly on the presence of "accessible" galactosyl or mannosyl residues in the Fc domain and that the modulation of the Fc-R function induced by these carbohydrates is due to a change in the affinity rather than in the number of single class of high-affinity binding sites.

HL-A and carpal tunnel syndrome.

One hundred and five patients suffering from carpal tunnel syndrome were HL-A typed. No linkage could be demonstrated between HL-A phenotypes and this syndrome.

Positive correlation between breast cancer incidence and HLA antigens.

HLA determinations were made at the time of diagnosis among a lot of 141 patients with breast cancer. Values of relative risk as well as frequencies of antigens at the first and the second locus were confronted to data found in a control population. Subdivisions of the neoplastic population according to hormonal status and parity led to the emergence of significant differences: frequency of A28 in menopausal nulliparous women with breast cancer is 26 vs. 7% in controls (p corrected = 0.038) with relative risk = 6.63 (p 0.001).

Glomerulonephritis due to transplant rejection affecting a patient's own kidneys.

The kidneys of a patient were removed 3 months after a cadaveric allograft; histological examination revealed tuberculosis and malignant nephroangiosclerosis. When examined one year later, the graft exhibited lesions of glomerulonephritis and of vascular rejection. Immunoglobulin deposits were shown by immunofluorescence in the patient's own kidneys as well as in the graft; they were isolated by acid elution and in both cases had lymphocytotoxic activity in vitro. It is suggested that the target organ released histocompatibility antigen with formation of antigen antibody complexes which deposited in the patient's own kidneys.