MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera.

Two regions of the genome contain members of the MAGE gene family; Xq27-qter and Xp21.3. We isolated a transcript, MAGE Xp-2, by screening a cDNA library from the human epithelial carcinoma cell line, HEp-2, using autoantibodies from patients with systemic lupus erythematosus (SLE). The open reading frame (ORF) of MAGE Xp-2 is entirely contained in exon 4, a signature feature of the MAGE gene family. While MAGE Xp-2 shares genomic homology with MAGE Xp-1, the predicted proteins are quite divergent. Specific primers were designed to reliably distinguish between MAGE Xp-1 and MAGE Xp-2 expression. MAGE Xp-2 is expressed in testis, but not in other normal tissues. It is also expressed strongly in two of seven melanoma cell lines and one of four breast carcinomas. MAGE gene expression may be important not only for tumor recognition and cancer therapy, but, because it is the apparent target of autoantibodies in SLE sera, it may also play a role in autoimmune diseases.

Peripheral blood lymphocytes with receptors for a determinant common to B-lymphoblastoid cell lines and acute myelogenous leukemia blasts.

We investigated whether the rosetting of B-lymphoblastoid cell lines (B-LCL) by peripheral blood lymphocytes (PBLs) reflected possible interactions between lymphoid cells and immature cells of the hematopoietic system. Rosette formation could be blocked by the addition of soluble antigen extracted from B-LCL or blasts obtained from patients with acute myelogenous leukemia (AML). This inhibition was specific for AML blasts (similarly extracted material from melanoma lines had no inhibitory effect) and for the B-LCL receptor (leukemic extracts had no effect on surface receptors for sheep red blood cells (E) or antibody-sensitized red blood cells (EA)). The B-LCL receptor is present on leukemic Sezary T-cells as well as normal T-cells and its sensitivity to various enzymatic treatments is markedly different from that of E and EA receptors. In addition, B-LCLs derived from in vitro EB-viral infection of a normal donor's B lymphocytes were significantly rosetted by that donor's autologous PBLs. These data suggests the B-LCL receptor, present on mature T-cells, can recognize self determinants on myeloblasts and B-LCL. Further investigation will determine whether this interaction can affect the function of rosetted target cells.

Acetylcholine receptor antibody titer and HLA-B8 antigen in myasthenia gravis.

In 82 white patients with myasthenia gravis, a high serum human acetylcholine receptor (AChR) antibody titer was related to the presence of the HLA-B8 antigen and increasing severity of the disease and not to age at onset, sex, presence of thymoma, or mode of treatment. Among patients without thymomas a high antibody titer was also associated with HLA-B8, particularly in those patients whose age at onset was less than 35 years. Thymectomy was associated with a lower median antibody titer when compared in two groups of HLA-B8-positive patients without thymoma who were similar for all other factors. Patients with thymomas who had received corticosteroids had a lower median titer than those who had not received steroids. This study supports the possibility that immune-response genes near the HLA-B8 segment of the major histocompatibility complex participate in the regulation of the humoral response to autoantigens, such as AChR protein.

Cell surface antigens detected on mature and leukemic granulocytic populations by cytotoxicity testing.

Using a microcytotoxicity assay, the serological reactivity of human granulocytes, namely neutrophils and eosinophils, and chronic myeloid leukemia (CML) cells and cultured CML cell lines (K562, NALM-1) were examined. Mature granulocyte forms and cord granulocytes are readily lysed by specific granulocyte cytotoxins that do not react with random T and B lymphocytes, monocytes, red blood cells, or platelets. Furthermore, certain antisera were preferentially cytotoxic for eosinophil-enriched populations. Granulocytotoxin detected antigens on one of three CML blast cell populations tested and K562, but failed to react with NALM-1. By cytotoxicity, mature granulocytes were poor targets for B2-microglobulin and the appropriate HLA antisera although both sera types are absorbed with granulocytes. Furthermore, granulocytes did not possess B-lymphocytes (Ia-like) or blood group A, B, and Rh (D) antigens. Except for K562, both HLA and heterologous B-lymphocyte antisera were cytotoxic for the CML blast cell populations tested.

Serological characterization of human monocytes for HLA, B-lymphocyte, granulocyte, and monocyte-associated antigens by cytotoxicity testing.

Highly enriched preparations of monocytes, B and T lymphocytes, and granulocytes from 18 normal donors were serotyped in parallel in a complement-dependent cytotoxicity assay using allogeneic and heterologous antisera defining three independent tissue antigen systems. HLA and B-lymphocyte tissue antigens were detected on human monocytes although granulocyte antigens were absent. By cytotoxicity testing the presence of Ia-like antigens on monocytes was significantly diminished compared to the autologous B-lymphocyte population and has important implications in B-lymphocyte serology. The study indentified a number of human antisera obtained from multitransfused subjects and pre- and post-transplant organ recipients that were non-HLA and appeared to define monocyte-associated antigens. The serological implications of surface antigen expression on human monocytes compared with other peripheral blood cells are discussed.

Bone-marrow transplantation in acute leukaemia.

Survival in 33 patients with resistant leukaemia treated by marrow transplantation was compared with that of 37 matched patients treated by conventional and experimental chemotherapy. All patients in the transplant group were rendered free of detectable leukaemia for periods of from 36 days to more than 2 1/2 years, while only 6 patients in the chemotherapy group achieved a haematological remission. Overall survival in both groups was poor; however, 5 patients (15%) in the transplant group remain alive and in haematological remission 1--2 1/2 years after transplantation, while no patient in the chemotherapy group survived longer than 13 months. Bone-marrow transplantation appears to offer a small but distinct possibility of long-term survival in patients with acute leukaemia resistant to conventional therapy.