PubMed · 6174471
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B Berman, H M Frankfort. The human interferon system.. https://doi.org/10.1111/j.1365-4362.1982.tb00478.x
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BACKGROUND: Cytotoxic IgG against class I antigens can contribute to renal dysfunction or failure after transplantation. However, the clinical relevance of IgG measured by flow cytometric cross-matching is controversial. This study correlated pre- and postoperative flow reactivity with clinical outcome among renal transplant patients with negative preoperative cytotoxic cross-matches. METHODS: Nonsensitized primary renal allograft patients (n = 157) with negative preoperative cytotoxic cross-matches (complement-dependent lymphocytotoxicity assays) were stratified on the basis of IgG reactivity measured by flow cytometric cross-matching (FCXM) as FCXM negative (Neg) or positive against class I (T-pos FCXM) or class II (B-pos FCXM) antigens. The groups were compared in terms of frequency of early rejection and 1-year graft survival. RESULTS: Patient distribution was 67% Neg, 14% T-pos FCXM, 14% B-pos FCXM, and 5% IgM FCXM. The incidence of early rejection was 25+/-3% for Neg and 51+/-3% for T- and B-pos FCXM (P < 0.05). One-year graft survival for Neg versus T-pos and B-pos FCXM was 97+/-3% versus 44+/-10% (P < 0.05) and 77+/-5% (P = 0.06), respectively. Rejections requiring plasmapheresis were found only among patients with T-pos FCXM. Among 29 patients, FCXM and complement-dependent lymphocytotoxicity assays were performed 10+/-2 and 28+/-4 days after transplantation. Pre- and posttransplant antibody levels were relatively unchanged among Neg and B-pos FCXM patient groups. In contrast, patients with T-pos FCXM produced cytotoxic IgG against class I after transplantation, which may have contributed to the severe graft dysfunction experienced by this group. CONCLUSIONS: FCXM is a useful tool to stratify primary renal transplant candidates in terms of potential risk for severe rejection. Furthermore, demonstration of preoperative flow reactivity against class I may identify a subgroup of patients at risk for early elaboration of cytotoxic alloantibody.
I have previously assumed that stem tumour cells are 'para-embryonal cells' (PECs) poor or missing in major histocompatibility complex (MHC) antigens. PECs might induce adjoining differentiated hyperplastic cells to also express tumoral phenotype and properties, thus transforming them into 'differentiated para-embryonal cells' (DPECs), MHC-endowed. In such a way, PECs, MHC-lacking, would be automatically surrounded by DPECs, MHC-endowed: this tumour organization was experimentally found by Cordon-Cardo et al in a variety of cancers. Now, I suggest that such a tumour histology might preferentially induce an anti-DPEC T cell immune response which, sparing PECs, might release increasing amounts of DPEC antigens in the peritumour site. DPEC antigens might increase synthesis of specific antibodies and subsequent immunocomplex formation at the peritumour site. Here, abundant immunocomplexes might react through their Fc pieces with CD16 receptors of antibody-dependent cell cytotoxicity (ADCC)-endowed immune cells (natural killer (NK) cells, macrophages, polymorphonuclear cells). These cells would thus be stimulated to secrete their lytic factors before and without their coming into contact with target tumour cells. On the other hand, abundant immunocomplexes at the peritumour site might massively activate the complement system, thus generating large amounts of C3b. C3b might react with CD11b receptors of NK cells, stimulating them to also secrete their lytic factors in an ectopic way at the peritumour site, thus impairing NK cytotoxicity. In such a way, in the absence of ADCC and NK cytotoxicity, a tumour cell enhancement might easily occur. In the light of these ideas, a strategy for antitumour immunotherapy and vaccine is then proposed.
A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger rise in [Ca2+]i, a greater level of NK cell activation, and a more rapid induction of activation-induced cell death (by apoptosis). Investigation of an independently phenotyped normal cohort revealed that all donors with a low binding phenotype are F/F homozygotes, while all phenotypic high binding donors have at least one V allele. Initial analysis of 200 patients with SLE indicates a strong association of the low binding phenotype with disease, especially in patients with nephritis who have an underrepresentation of the homozygous high binding phenotype. Thus, the FcgammaRIIIa polymorphism at residue 176 appears to impact directly on human biology, an effect which may extend beyond autoimmune disease characterized by immune complexes to host defense mechanisms.