Reactivity of human monoclonal immunoglobulins (HMI) with autoantigens

42 Impaired Measles-Specific Cytotoxic T-cell response in SSPE Suhayl S. Dhib-Jalbut, M.D., Steven Jacobson Ph.D., Dale E. McFarlin, M.D., Henry F. McFarland, M.D. Neuroimmunology Branch, Bldg lO, Rm. 5B-16, NINCDS NIH, 9000 Rockville Pike, Bethesda, MD 20892 Subacute sclerosing panencephalitis (SSPE) is a persistent infection of the nervous system related to measles virus (MV). I t is not known whether a defect in the host c e l l u l a r immune response to MV exists in this disease. The capacity to generate MV-specific cytotoxic T-Lymphocytes (CTLs) was examined in two SSPE patients and eight healthy controls, using autologous MV infected B-cell targets in a standard Cr-release assay. The a b i l i t y to generate influenza and mumps virus-specific CTLs was used as a control response. MVspecific CTL response was markedly reduced in both SSPE patients (<5%) compared to that in the healthy controls (24.1 ± 9.1%). Generation of influenza and mumps virus-specific CTLs, as well as MV induced NK a c t i v i t y were similar in the SSPE patients and controls. In addition, MHC class I I matched CTLs from healthy individuals lysed SSPE targets indicating a defect in the effector cell in SSPE. The results indicate a defect in generation of MY-specific CTLs in these two patients, which could relate to persistence of MV in SSPE.

Reactivity

Of

Human

Monoclonal

Immunoglobulins

(HMI)

With Autoantigens

Michael E. Dieperink, Linda S. Matron and Karl Stefansson Departments of Neurology and Pathology (Neuropathology) University of Chicago, Chicago, IL 60637

Existence of naturally occurring autoantibodies (NA) in humans is well document. It is possible that NA demonstrated by conventional methods form only the tip of the iceberg and there may be a large pool of NA that are in too low concentration to be detected. It is also likely that monoclonal gammopathies (MCGP) giving rise to HMI result from expansion of clones of B-cells or plasma cells without changes in speclficities of antibodies produced by the cells. Hence, it is likely that specificities of HMI reflect specificities of normal Ig. To estimate prevalence of NA, we looked at sera from 76 MCGP patients (14 IgG ~, 32 IgGK , 3 IgM~ , 14 IgMK , 7 IgA X , 6 IgA ~ ) on immunoblots containing polypeptides from homogenates of white matter, spinal cord, peripheral nerve, kidney and macrophages. Sera were diluted such that concentration of HMI was equivalent to IgG in normal serum diluted 1/100. Following proportion of HMI reacted specifically with at least one polypeptlde in at least one of the homogenates: IgG 28%, IgM 53%, and IgA 31%. These results indicate that NA make up a large percentage of antibodies in normals. These results also underscore the necessity to exercise caution when granting HMI roles in pathogenesis of disorders occurring in patients with MCGP that involve tissues the RMI react with.