Expression of the common acute lymphoblastic leukaemia antigen (CALLA) in the human breast

A biochemical and immunohistological study has been carried out to characterize the antigen in human breast reacting with antibodies to the common acute lymphoblastic leukaemia antigen (CALLA). Four different monoclonal antibodies to the CALLA antigen all stain the membrane of adult human myoepithelial cells. Surface labelling studies of freshly prepared human breast cells demonstrate that the anti-CALLA antibody, J5, immunoprecipitates a 100 kDa protein that co-electrophoreses with the CALLA antigen identified in the leukaemia cell line NALM-6. These results indicate that the CALLA antigen is expressed on myoepithelial cells and that the staining is not due to reactivity with a shared epitope on an unrelated molecule.     

Detection of the common acute lymphoblastic leukemia antigen in the serum of leukemia patients.

The common acute lymphoblastic leukemia antigen (CALLA) has been detected in biological fluids using a radioimmunoassay based on the inhibition of binding of 125I-labeled monoclonal anti-CALLA antibody to glutaraldehyde-fixed NALM-1 cells. With this assay, we showed first that CALLA was released in culture fluids from NALM-1 and Daudi cell lines but was absent from culture fluids from CALLA negative cell lines. Then, we found that the sera of 34 out of 42 patients (81%) with untreated common acute lymphoblastic leukemia (c-ALL) contained higher CALLA levels than any of the 42 serum samples from healthy controls. The specificity of these results was further demonstrated by testing in parallel the sera from 48 patients with CALLA negative leukemias, including 26 acute myeloid leukemia (AML), 12 T-cell acute lymphoblastic leukemia (T-ALL), and 10 acute undifferentiated leukemia (AUL). All of these sera gave negative results, except for one patient with AUL, who had a significantly elevated circulating CALLA level, and one patient with AML, who had a borderline CALLA level, 3 SD over the mean of the normal sera. Preliminary results suggest that circulating CALLA is associated with membrane fragments or vesicles, since the total CALLA antigenic activity was recovered in the pellet of the serum samples centrifuged at 100,000 g. In addition, the CALLA-positive pellets contained an enzyme considered as a membrane marker, 5'-nucleotidase. Evaluation of the clinical importance of repeated serum CALLA determinations for the monitoring of c-ALL patients deserves further investigation.     

A unique cell surface antigen identifying lymphoid malignancies of B cell origin.

A monoclonal antibody (anti-B1) specific for a unique B cell surface differentiation antigen was used to characterize the malignant cells from patients with leukemias or lymphomas. All tumor cells from patients with lymphomas or chronic lymphocytic leukemias, bearing either monoclonal kappa lambda light chain, expressed the B1 antigen. In contrast, tumor cells from T cell leukemias and lymphomas or acute myeloblastic leukemia were unreactive. Approximately 50% of acute lymphoblastic leukemias (ALL) of non-T origin and 50% of chronic myelocytic leukemia in blast crisis were also anti-B1 reactive. moreover, 21 of 28 patients with the common ALL antigen (CALLA) positive form of ALL were anti-B1 positive, whereas 0 of 13 patients with CALLA negative ALL were reactive. These observations demonstrate that an antigen present on normal B cells is expressed on the vast majority of B cell lymphomas and on approximately 75% of CALLA positive ALL, suggesting that these tumors may share a common B cell lineage.     

Leukemia-specific serum from a child showing an immunofluorescent pattern distinct from J-5 monoclonal antibody directed for CD10 (common ALL antigen)

Leukemia-specific human antibody was detected in a child with acute lymphoblastic leukemia (ALL) treated with chemoimmunotherapy. Chemoimmunotherapy consists of standard chemotherapy and subcutaneous injections of irradiated ALL cells with a biological response modifier. This ALL-specific serum reacted in 60 out of 67 (89.5%) children with ALL and was not reactive with normal cells. Furthermore, this ALL-specific serum showed a different immunofluorescent pattern on dual staining as compared with J-5 monoclonal antibody directed for common ALL antigen (CALLA; CD10). J-5 did not block the reactivity of ALL-specific serum, and vice versa, when CD10-positive ALL cell lines were used as targets. These findings suggest the possibility that there exists an ALL-specific antigen(s) which is different from CALLA and that this antigen(s) elicits a tumor-specific antibody response.     

Quantitative variation of the common acute lymphoblastic leukemia antigen (gp100) on leukemic marrow blasts.

Marrow blasts from children with B cell precursor acute lymphoblastic leukemia (ALL) were studied for differences in quantitative expression of the common ALL antigen (CALLA). Of 42 untreated patients, 35 had detectable amounts of CALLA by flow cytometric (FCM) analysis of J-5 monoclonal antibody binding. Using an FCM technique that provides correlated measurements of a given cell surface antigen, cell size, and DNA content, we detected increased CALLA expression as lymphoblasts moved from G0/G1 phase through S phase of the cell cycle. The density of the antigen (per unit of blast surface area) remained relatively constant over the same interval, indicating that the change was not due to S phase-specific enhancement of CALLA expression. Eight cases had hyperdiploid cellular DNA content and in seven of these, only cells with clonal abnormalities of DNA content expressed the CALLA marker. Mean amounts of CALLA for each patient ranged widely within the study group, from very high to marginally detectable. This variation had no discernible relation to cell size, stem-line DNA content, percentage of cells in S phase, or the presence or absence of cytoplasmic immunoglobulin. Results of a univariate proportional hazards analysis showed that both quantitative level of CALLA for S phase cells (P = 0.048) and white blood cell count (P = 0.012) had made significant contributions to treatment outcome. Patients with relative amounts of CALLA less than the median value for the entire CALLA+ group had a higher rate of failure, which was virtually identical to that for the seven HLA-DR+ patients whose blasts lacked detectable CALLA. The observed interpatient variation in quantitative expression of CALLA is consistent with recognized steps in B cell precursor differentiation and may be useful in distinguishing patients with a less favorable prognosis.     

Establishment of five human malignant non-T lymphoid cell lines and mixed lymphocyte-tumor reaction

Five human malignant non-T lymphoid cell lines have been established. THP-4 and THP-7 were derived from two children with common type acute lymphoblastic leukemia (ALL), THP-6 and THP-8 from two children with null cell type ALL and THP-9 from a child with malignant lymphoma. THP-4 was positive for cytoplasmic mu, B4, common ALL antigen (CALLA) and Ia-like antigen (Ia), THP-7 positive for B4, CALLA and Ia, THP-8 positive for B4 and Ia, and THP-9 positive for surface mu-lambda, B1, B4, CALLA and Ia. No antigenic determinants for monoclonal antibodies used were detected on THP-6. THP-4, THP-7, THP-8 and THP-9 were able to stimulate allogeneic lymphocytes vigorously. THP-6 without Ia stimulated not only allogeneic lymphocytes, but also autologous ones. THP-7 did not stimulate autologous lymphocytes.     

Induction of human B cell antigens in non-T cell acute lymphoblastic leukemia.

Leukemic cells from 70% of patients with Ia+CALLA+ non-T cell acute lymphoblastic leukemia (ALL) express an antigen (B1) found on all normal B lymphocytes. In this study, ALL cells that do not express the B1 antigen were studied in an attempt to further elucidate the cellular lineage of these tumors. Non-T cell ALL lines and tumor cells isolated from patients with non-T cell ALL that are Ia + CALLA + B1- were studied in vitro with a variety of agents known to promote cellular differentiation. Phorbol diester (TPA) or phytohemagglutinin conditioned leukocyte culture media were capable of inducing the expression of B1 on all four non-T cell ALL lines tested. In contrast, B1 could not be induced under the identical conditions on a promyelocytic leukemia line or a T cell lymphoblastic leukemia line. With the induction of B1 on non-T cell ALL lines, cytoplasmic mu-heavy chain (c mu) became undetectable, whereas the expression of CALLA and Ia were unchanged. The expression of B1 was accompanied by a decrease of cellular proliferation and DNA synthesis, but not significant morphologic changes were noted. In addition, no other B or T cell antigens were detected. The cellular origin of non-T cell ALL was further investigated using tumor cells isolated from leukemic patients. Tumor cells from eight patients with Ia + CALLA + B1-c mu- ALL could be induced in vitro with TPA to express both B1 and c mu. In contrast, cells from five patients with Ia + CALLA-B1-c mu- non-T cell ALL could not be induced with TPA to express CALLA, B1 or c mu. These studies suggest that the non-T cell ALL are heterogeneous and represent a spectrum of early B cell differentiation including the pre- pre-B cell (Ia + CALLA + B1-c mu-), the intermediate pre-B cell (Ia + CALLA +B1 + c mu-), and finally the "true" pre-B cell (Ia + CALLA + B1 + c mu+). The cellular origin of the remaining Ia + CALLA-B1-c mu- form of non-T cell ALL (20%) is still unknown.     

Common acute lymphoblastic leukemia antigen expressed on leukemia and melanoma cell lines has neutral endopeptidase activity.

We have previously reported that the amino acid sequence of the common acute lymphoblastic leukemia antigen (CALLA, CD10) translated from a normal human kidney cDNA clone is identical to that of neutral endopeptidase (NEP, EC 3.4.24.11). In this study, we show that by flow cytometry, a monoclonal antibody (135A3) produced against rabbit NEP reacted selectively with leukemia and melanoma cell lines expressing CALLA on their surface. A glycoprotein of apparent Mr 100,000 was immunoprecipitated from surface labeled NALM-1 leukemia or Mel-1477 melanoma cells with monoclonal antibodies to NEP (135A3) or CALLA (44C10). mRNAs hybridizing to a NEP-specific probe were present in CALLA+ leukemia and melanoma cell lines, but absent from CALLA- lines. NEP enzymatic activity was detected on intact cells from CALLA+ lines, but not CALLA- lines. The activity was blocked by two selective inhibitors of NEP, thiorphan and phosphoramidon. CALLA antigen purified from the NALM-6 leukemic cell line by affinity to 44C10-IgG Sepharose retained a peptidase activity that was completely blocked by thiorphan and phosphoramidon. Thus the CALLA antigen present at the surface of leukemia and melanoma cell lines is an enzymatically active neutral endopeptidase.     

The common acute lymphoid leukemia antigen on b cells of chronic lymphoid leukemia and non-Hodgkin's lymphoma

Fourteen out of 21 non-Hodgkin lymphoma (NHL) and 3/11 chronic lymphoid leukemia cells (CLL) had the common acute lymphoid leukemia antigen (CALLA) All 32 patients had monoclonal B-cell proliferation. The CLL patients had 90% CALLA positive cells while the proportion of their leukemic elements was superior. Lymph-nodes or bone marrow invaded by a B monoclonal tumor cell population of NHL had significantly more CALLA positive cells (42.1 +/- 32.5%) than non-invaded tissues (11.4 +/- 10.3%). In NHL tissues with monoclonal B-cells, lymph-nodes had significantly more CALLA positive cells (56.0 +/- 29.9%) than marrow (23.5 +/- 27.7%). It is well known that the (CALLA) is not specific for ALL. It has been believed to be a differentiation antigen on pre B-cells. The present study confirms that it also occurs on B-cells (2,4,6,7,8,9,10,11).     

Measurement of anti-IgA antibodies by a two-site immunoradiometric assay

To enable the detection of IgG class, anti-IgA antibodies (IgG-aIgA) and to investigate the possible occurrence of IgE class, anti-IgA antibodies (IgE-aIgA), we developed a solid phase immunoradiometric assay (IRA), which uses purified IgA coupled covalently to microcrystalline cellulose as an immunosorbent. Radiolabeled, Fc specific anti-IgG and anti-IgE antibodies were used to detect specific aIgA after incubation of test sera or controls with the immunosorbent. IgG-aIgA were detected by the IRA in 100 and 67 per cent of control sera with class specific and limited specificity aIgA. The IRA was sensitive to approximately two ng of class specific IgG-aIgA. IgG-aIgA also were detected by IRA in 7.9 per cent of sera from patients with urticarial transfusion reactions and 73 per cent of sera from patients with ataxia telangiectasia and IgA deficiency. Sera from 50 normal blood donors did not have detectable IgG-aIgA. Tests for IgE-aIgA were negative in all cases, including control sera with class specific IgG- aIgA. We conclude that the IRA is a sensitive and reproducible method for detection of class specific and limited specificity IgG-aIgA, and that IgE-aIgA do not mediate urticarial transfusion reactions.     

Immunologic phenotypes of germinal center cell tumors

A panel of monoclonal antibodies applied to frozen sections of non-Hodgkin's lymphomas was used to establish clear-cut differences among the different entities of malignant lymphomas of germinal centre cell origin. 51 cases (18 centrocytic, 25 centroblastic-centrocytic and 8 centroblastic lymphomas) were included in this study. A clear-cut difference in the expression of the T65 antigen (Leu 1+) and the common acute lymphoblastic leukaemia antigen (CALLA) was found. Thus, centrocytic lymphomas predominantly expressed Leu 1, but not CALLA, whereas centroblastic-centrocytic lymphomas were always positive for CALLA, but not for the T65 antigen. Centroblastic lymphomas are virtually never positive with respect to either antibody. These findings suggest that, perhaps, two different phenotypes of centrocyte exist in centrocytic and centroblastic-centrocytic lymphomas.     

Scl-86, a marker antigen for diffuse scleroderma.

More than 300 sera from patients with a connective tissue disease were analyzed with the immunoblotting technique. The presence of autoantibodies against an 86,000-mol wt marker antigen for diffuse scleroderma (Scl-86) was found in 14 out of 33 patients with scleroderma. The presence of anti-Scl-86 antibodies seemed to correlate with the diagnosis of diffuse scleroderma since they were found in 13 out of 22 diffuse scleroderma patients and in only one out of 11 patients with limited scleroderma. All scleroderma sera (33 patients' sera and 13 reference sera) were also tested for the presence of anti-Scl-70 antibodies. It was found that all anti-Scl-70 positive sera (n = 25) contained anti-Scl-86 antibody as well, suggesting a relationship between these two antigens. However, the Scl-86 antigen was shown to be an extremely insoluble nonchromosomal protein, resistant to boiling in sodium dodecyl sulfate. This contrasts with the Scl-70 antigen, which has been described as a thermolabile, soluble antigen present in the chromatin fraction. Together, our results are consistent with the idea that Scl-70 is a degradation product of Scl-86. The Scl-86 antigen is present in freshly prepared rabbit thymus, spleen, and liver nuclei as well as in nuclei from various cultured cell lines, but is not detectable in extractable nuclear antigen from rabbit thymus. In a limited retrospective study, the anti-Scl-86 antibodies were found in two sera from patients with Raynaud's phenomenon before the development of diffuse scleroderma. Therefore, it is possible that screening of patients' serum for this antibody might predict the development of diffuse scleroderma.     

Requirements for the construction of antibody heterodimers for the direction of lysis of tumors by human T cells.

We constructed a series of MAb heterodimers consisting of the J5 (anti-common acute lymphoblastic leukemia antigen [CALLA]) antibody and antibodies to a variety of structures present on the surface of activated human T cells, including CD3 antigen (T cell receptor-associated glycoproteins), CD2 antigen (T11/E-rosette receptor), CD25 antigen (IL-2 receptor), and the transferrin receptor. We tested the ability of these heterodimers to direct a CD2 + CD3 + CD8 + CD4 - CD25 + transferrin receptor + MHC-restricted human cytolytic T lymphocyte (CTL) clone to lyse a CALLA + human tumor in vitro. Only heterodimers containing an anti-CD3 antibody or activating antibodies to CD2 could direct the clone to lyse these human tumor targets, even when the clone was additionally activated with anti-CD3 or anti-CD2 antibodies. Our findings may have implications in the design of strategies for the use of such reagents in the treatment of human neoplasia.     

Elevated Levels of Antibodies to Epstein-Barr Virus Antigens in Sera and Synovial Fluids of Patients with Rheumatoid Arthritis

The frequencies and levels of antibodies to Epstein-Barr virus (EBV)-specific antigens were determined in paired sera and synovial fluids from patients with rheumatoid arthritis (RA) and in sera from patients with other connective tissue diseases; i.e., systemic lupus erythematosus, progressive systemic sclerosis, and osteoarthritis (OA). The specimens were also tested for the presence of antibodies to RA-associated nuclear antigen. Compared to healthy controls, the patients' sera showed increased frequencies of elevated antibody titers (≥320) to Epstein-Barr viral capsid antigen, a correspondingly enhanced (twofold to threefold) geometric mean titer, and an increased frequency of antibodies at elevated titers (≥10), usually to the restricted component and rarely the diffuse component of the early antigen complex. Levels of antibody to the EBV-associated nuclear antigen were within the normal range. Enhancement of antibody titers was more pronounced in seropositive RA patients (i.e., positive for rheumatoid factor) than in those who were not. Enhancement was also found in systemic lupus erythematosus and progressive systemic sclerosis. Antibody to RA-associated nuclear antigen was detected at an increased frequency only in the group of seropositive RA patients (90%), as compared to 8-15% in the other connective tissue diseases and 6-8% in healthy controls. The antibody titers in the synovial fluids equaled or were at most twofold higher or lower than those in the sera. In addition, levels of EBV-specific antibodies were studied serially over a period of 6-10 mo in patients with RA and OA. Parameters of disease activity were determined and compared to antibody levels. EBV-specific antibodies in sera of OA patients remained constant and within normal limits throughout the study. Although EBV-specific antibodies were often elevated in RA patients, they also remained constant, with the exception of three patients, who showed gradual increases in one of the four antibodies, which did not correlate with disease activity.     

A cocktail of affinity-purified antibodies reactive with diagnostically useful mycobacterial antigens ES-31, ES-43, and EST-6 for detecting the presence of Mycobacterium tuberculosis

A cocktail of affinity-purified antibodies against diagnostically useful Mycobacterium tuberculosis H37Ra excretory-secretory protein antigens ES-31, ES-43, and EST-6 was explored for detection of circulating free and immune-complexed (IC) antigen in sera of patients with confirmed tuberculosis (TB) by sandwich enzyme-linked immunosorbent assay and compared with monospecific anti-ES-31 antibody. Out of 68 smear-positive TB cases studied, using cocktail antibody, a sensitivity of 97% (66/68) for immune-complexed cocktail antigen and 91% (62/68) for free cocktail-antigen detection was observed, compared to 91% (62/68) for immune-complexed ES-31 and 79% (54/68) for free ES-31 antigen when anti-ES-31 antibody was used alone. Thus, combinatorial use of antibodies showed improved sensitivity and was thus observed to be better than single antibody. The specificity was observed to be 99% for immune-complexed antigen using cocktail antibody. Furthermore, analysis of different groups of TB sera showed that circulating immune-complexed antigen is a sensitive marker than free antigen.     

Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all CALLA+ cells were Ia+ and expressed two activation antigens, J2 and T10, only 30-50% expressed B1 antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal, purified CALLA+ cells demonstrated that incubation at 37 degrees C with J5 monoclonal antibody specific for CALLA resulted in the specific modulation of surface antigen. Similar results have previously been obtained with CALLA+ tumor cells. Although phenotypic analysis of CALLA+ cells suggests that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells.     

RELATION BETWEEN EPSTEIN-BARR VIRAL AND CELL MEMBRANE IMMUNOFLUORESCENCE IN BURKITT TUMOR CELLS : IV. DIFFERENTIATION BETWEEN ANTIBODIES RESPONSIBLE FOR MEMBRANE AND VIRAL IMMUNOFLUORESCENCE

Previous reports (1, 2) have established that the expression of certain distinctive membrane antigen(s) on the surface of Burkitt's lymphoma (BL) and infectious mononucleosis (IM) cells is dependent on the presence of Epstein-Barr virus (EBV) in the cell line. The investigations reported here provide evidence that antibodies directed against EBV antigens, as revealed by the immunofluorescence test on acetone-fixed smears (8), and the membrane reactive antibodies, although often present in the same serum, are nevertheless distinctly different. Absorption of Mutua serum, the standard reference serum for demonstrating membrane antigen(s) on BL and IM cells, with BL cells completely removed anti-membrane activity without significantly affecting the anti-EBV antibody titer. Furthermore, sera were found which contained one type of antibody but not the other. Sera with high anti-membrane but low anti-EBV activity were found among relatives of BL patients. These sera reacted with the membranes of EBV-carrying BL and IM cells in essentially the same way, i.e., against the same spectrum of target cells, as the EBV-positive Mutua serum. They were unable to block the membrane reactivity of FITC-conjugated Mutua serum, however. In some cases they showed weak but incomplete blocking. One such EBV-negative, membrane-positive BL relative serum (Robert) was conjugated with FITC and used for direct staining of BL and IM cells. Again, this conjugate reacted against the same target cell spectrum as a Mutua conjugate, but its reactivity was completely blocked by a number of Burkitt patients' sera, although unconjugated Robert serum did not block the Mutua-conjugate. A number of other membrane-positive BL relative sera also failed to block Mutua, but completely blocked the Robert conjugate. A number of Swedish and African control sera and an isoantiserum gave no blocking against Robert conjugate. It therefore appears that the Mutua conjugate contains at least two antibody specificities against the EBV-determined membrane antigens. One, but not the other, is shared with the antibody specificity present in Robert's serum and a number of other sera from relatives of BL patients.     

Detection of antibodies in sera from patients with Opisthorchiasis

The indirect immunofluorescent antibody technique (IFA) was used for detection of antibodies in sera of patients with Opisthorchiasis. Antibodies to fluke worm and egg antigens were detected in 166 of 205 (81%) patients. The test showed that only the IgG class of antibodies reacting exclusively with integumental wall of the worm (AW) were positive in 46.8% (96/205), reacting only with the wall of intact eggs in 11 out of 205 (5.4%) and antibodies to both fluke and their egg antigens were present in 28.8% (59/205). In addition, 5.4% (11/205) of patients' sera were positive for autoantibodies producing a speckled antinuclear antibodies (ANA) pattern. The sera positive for only AW contained detectable autoantibodies to other cell antigens including: anti-smooth muscle antibodies of 9.4% (9/96), antimitochondrial antibodies of 3.1% (3/96), anti-liver/kidney microsomes of 1% (1/96) and anti-parietal cell antibodies of 1% (1/96). Autoantibodies were undetectable in sera from normal subjects. Among the ANA positive sera, 55% (6/11) exhibited antibodies against an extractable nuclear antigen (ENA) by a tanned red cell hemagglutination assay. This finding may suggest that the autoantibody response was due to the cross reaction between worm antigen and self antigen or it may be the result of polyclonal activation of B lymphocytes in these patients.     

Acid pH-induced changes in the immunoreactivity of specific antigen and antibody in circulating immune complexes from tuberculosis sera.

The effect of acid pH treatment of circulating immune complexes (CIC) derived from tuberculosis sera was studied on the relative titers of specific antibody (CIC Ab) and mycobacterial antigen (CIC Ag) in the complexes. While the specific antibody titers increased, the titers of CIC Ag declined as a result of acid pH treatment of CIC, both changes being highly significant statistically. Direct exposure of TB sera to pH 2.8 also resulted in significant enhancements in the titers of antibodies directed against Mycobacterium tuberculosis (M.tb.). Competition experiments indicated that the acid pH-treated antibodies retained their antigen specificity. TB sera treated with pH 2.8 for 30 min and then neutralized back to pH 7.4 retained the enhanced antibody reactivity even after 7 days of storage at 4 degrees C. Our results indicate that acid pH treatment induces higher antigen binding ability in anti-M.tb. antibodies, present in free or complexed form in TB sera. These changes appear to be irreversible. Dissociation of CIC and analyzing the titers of released antibody and antigen components offered no advantage with respect to the immunodiagnosis of tuberculosis, as compared to the levels of undissociated CIC components or the serum antibody.     

Detection of antibody to a new antigen induced by Epstein-Barr virus in rheumatoid arthritis.

A new antigen which is different from Epstein-Barr virion antigen was detected in NC-37 cells infected with Epstein-Barr virus (EBV). A significant elevation of the titer of antibody to this new antigen was observed in the sera of the patients with rheumatoid arthritis (RA), but not in the sera of controls. From the standpoint of the etiologic role of EBV in RA, it is interesting that the antibody to the new antigen is not detected in the healthy persons in contrast to other viral antibodies. Therefore, it differs from any other viral antibodies so far reported.