Chronic parvovirus B19 infection induces the production of anti-virus antibodies with autoantigen binding properties.

Human parvovirus B19 infection in adults shows some clinical features similar to those found in autoimmune connective tissue diseases. To better clarify the relationship between viral infection and autoimmunity, we have evaluated the ability of anti-parvovirus antibodies to specifically recognize autoantigens in ten patients with chronic symmetric arthritis resembling rheumatoid arthritis or with recurrent episodes of arthritis and cutaneous manifestations and persistence of specific IgM antibodies against B19 parvovirus. We synthetized a 24-amino acid immunodominant peptide corresponding to a part of the virus protein 1 and virus protein 2 overlapping region. The peptide has been used to test patients' sera at different time points with an enzyme-linked immunosorbent assay (ELISA) and to purify anti-virus antibodies by affinity chromatography on a peptide-Sepharose column. Eluted immunoglobulins recognized the B19 peptide in both direct and competitive ELISA. Affinity-purified anti-parvovirus antibodies were then tested on a panel of autoantigens including human keratin, collagen type II, thyreoglobulin, single-strand (ss)DNA, cardiolipin and ribonucleoprotein antigen Sm. Eluted antibodies specifically recognized keratin, collagen type II, ssDNA and cardiolipin. Autoantibody activity was not detected in the immunoglobulin fraction after complete removal of anti-peptide antibodies and in antibodies eluted from normal donors. Epstein-Barr virus-transformed cell clones obtained from two subjects produced antibodies which simultaneously recognize the viral peptide and several autoantigens. To further confirm the role of the virus in inducing an autoantibody response, eight BALB/c mice were immunized with the viral peptide coupled to a carrier protein. Autoantibody activity against keratin, collagen II, cardiolipin and ssDNA was detected in six of the eight mice which developed a strong anti-virus response. Together, these data indicate that B19 parvovirus may be linked to the induction of an autoimmune response.

Biochemical characterization and membrane expression of an antigen shared by activated and neoplastic cells of neuroectodermal origin.

The reactivity of a mAb (M16) raised against a small cell lung carcinoma line is described. M16 identifies a surface antigen expressed on cells of neuroectodermal origin following activation, as well as neoplastic transformation. M16 antigen expression is increased on retinoblastoma and neuroblastoma cell lines upon 'in vitro' stimulation and it is induced 'in vivo' on glial cells activated following brain injury. Furthermore, glial tumors show levels of M16 molecule expression increasing with the degree of malignancy, and in a retinoblastoma cell line, the expression of M16 was inversely related to the level of HLA-Class I and N-CAM antigens. The M16 antigen may represent a marker of both activation and neoplastic progression for neuroectodermal cells.

Taxol cytotoxicity on human leukemia cell lines is a function of their susceptibility to programmed cell death.

Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol induces DNA fragmentation and the appearance of morphological features consistent with the process of apoptosis. Taxol-induced apoptosis is inhibited neither by cycloheximide nor by actinomycin D and therefore appears to be independent of new protein synthesis. Taxol causes arrest in the G2 phase of the cell cycle and affects cell viability but does not induce DNA fragmentation in the K562 erythromyeloid cell line. Protein-synthesis inhibitors, colcemid, ionomycin, and starvation, known to trigger apoptosis, proved ineffective as well. These results suggest that the antineoplastic effect of taxol is mediated in susceptible cell lines by induction of the apoptotic machinery and that K562 partial resistance may depend upon the intrinsic inability of these tumor cells to undergo apoptosis.