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Z M Sthoeger

Publications and source records attributed to Z M Sthoeger.

43 records · Page 3Linked to original sources
PubMed1991

Transient anticardiolipin antibodies, functional protein S deficiency, and deep vein thrombosis.

A 30-year-old man presented with an episode of deep vein thrombosis. He was found to have primary antiphospholipid syndrome with anticardiolipin antibodies and protein S deficiency. All other investigations were negative. Three months later, anticardiolipin antibodies were negative and protein S levels were normal. The transient presence of anticardiolipin antibodies and functional protein S deficiency in this patient suggests a new mechanism for the association between anticardiolipin antibodies and venous thrombosis.

Adult↗
PubMed1989

Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen.

The Ku (p70/p80) autoantigen consists of two phosphoproteins of molecular mass approximately 70,000 and 80,000 forming a macromolecular complex that binds DNA. Autoantibodies from a patient with systemic lupus erythematosus were used to isolate cDNA clones encoding the human approximately 70-kDa Ku antigen (p70) from a lambda gt11 expression library. The deduced amino acid sequence of p70 consisted of 609 amino acid residues and was confirmed by partial amino acid sequencing. The protein contains two acidic domains of 61 residues (31% Glu + Asp) and 19 residues (53% Glu + Asp) that are similar in size and charge to those found in a number of proteins involved in transcriptional activation. The 61-residue acidic region is rich in serine, raising the possibility that its charge might be modulated by phosphorylation. The predicted amino acid sequence also contains two regions with periodic repeats of either leucine alone, or leucine alternating with serine every seventh position. The latter repeat displays sequence and secondary structural similarities with the "leucine zipper" regions of the c-myc and v-myc oncogene products. The p70 antigen does not appear to have extensive sequence homology with the 80-kDa Ku autoantigen based on analysis of RNA blots and immunological criteria. A major antigenic determinant or determinants recognized by human autoantibodies is located near a leucine repeat on the carboxyl-terminal 190 amino acid residues of p70.

Amino Acid Sequence↗
PubMed1989

Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia.

CD5-expressing B lymphocytes from patients with selected chronic lymphoproliferative disorders were used to determine whether monoclonal populations of CD5+ human B cells produce autoantibodies. CD5+ B cells from 19 patients with chronic lymphocytic leukemia (CLL) and one with diffuse well-differentiated lymphocytic lymphoma (DWDL) were cultured, with and without mitogenic stimulation, to obtain Ig from these cells. 17 of the 20 samples produced Ig in vitro. mAb from nine of the 17 patients were reactive with either IgG, ssDNA, or dsDNA. In every instance, the autoantibodies displayed monotypic L chain usage that correlated precisely with the L chain expressed on the CD5+ leukemic B cell surface. These monoclonal autoantibodies varied in their degree of antigenic specificity; some were quite specific, reacting with only one antigen, whereas others were polyspecific, reacting with two or all three autoantigens tested. Three features distinguish these autoantibodies from those observed in prior studies of CD5+ B cells. First, they are clearly the products of monoclonal populations of CD5+ cells; second, several react with dsDNA, a specificity not previously reported and often seen in association with significant autoimmune disorders; and third, two of the monoclonal autoantibodies secreted by the CD5+ clones were of the IgG class. Although not all of the Ig-producing, CD5-expressing clones elaborated mAbs reactive with the autoantigens tested, greater than 50% did. It is possible that with a broader autoantigenic panel or with larger quantities of CLL/DWDL-derived Ig, even more autoantibody-producing clones might be identified. These studies may have important implications for the antigenic specificity of subsets of human B lymphocytes as well as for lymphoproliferative and autoimmune disorders in general.

Antibody Specificity↗
PubMed1989

Role of antigen selectivity in autoimmune responses to the Ku (p70/p80) antigen.

Levels of anti-Ku (p70/p80) antibodies were measured longitudinally in sera from four individuals with systemic lupus erythematosus or related disorders. Antibodies to the native Ku antigen (p70/p80 complex) varied over a range of up to 577-fold. Large fluctuations were also observed in the levels of autoantibodies to several distinct epitopes of the Ku (p70/p80) antigen. Levels of these individual autoantibody populations generally paralleled one another, suggesting that they are coordinately regulated. A similar pattern of anti-DNA antibody fluctuation was seen in some sera. To examine the possibility that these autoantibodies were generated by polyclonal B cell activation, the levels of anti-Ku (p70/p80) and anti-DNA antibodies were compared to the levels of antibodies to Escherichia coli proteins, tetanus toxoid, and bovine insulin, transferrin, cytochrome c, serum albumin, and thyroglobulin. In sera from the same individual, anti-Ku (p70/p80) antibodies were sometimes produced in the complete absence of polyclonal activation, and at other times were accompanied by increased polyclonal activation. Anti-DNA antibody levels more closely paralleled the level of polyclonal activation than did the anti-Ku (p70/p80) levels. These studies suggest that anti-Ku (p70/p80) antibodies are generated by an antigen-selective mechanism, but that polyclonal activation frequently, although not invariably, accompanies autoantibody production. This observation is consistent with the possibility that polyclonal activation might be secondary to autoantibody production.

Adult↗
PubMed1988

Regulation of the immune response by sex hormones. I. In vitro effects of estradiol and testosterone on pokeweed mitogen-induced human B cell differentiation.

Sex hormones have been implicated in the pathogenesis of many autoimmune disorders, presumably through regulatory influences on the immune system. However, the mechanisms of sex steroid action on humoral and cellular immune responses are not precisely understood. In this study, the in vitro effects of physiologic concentrations of 17 beta-estradiol and testosterone on the Ag non-specific differentiation of human PBMC were examined using optimal and sub-optimal doses, respectively, of PWM. In cultures of PBMC from 14 normal donors (7 men and 7 women, aged 25 to 45 yr), 17 beta-estradiol (0.5 to 30 ng/ml) enhanced PWM-induced generation of PFC by 46% (p less than 0.01), whereas testosterone (10 to 300 ng/ml) inhibited PFC generation by a mean of 36% (p less than 0.001). The enhancing and suppressing effects of the sex steroids on PBMC occurred early inasmuch as estradiol and testosterone had to be added to the cultures at their initiation (6 and 24 h, respectively) in order to observe their influence. Moreover, deletion of the hormones from the cultures after as short a period as 12 h did not obviate their effects. There was no alteration of the kinetics of the response to PWM or an effect on the number of spontaneous PFC generated in vitro in the absence of PWM. In addition, there was no difference among men and women in response to either sex steroid, and within the female group, no variation was observed on different days of the menstrual cycle. These studies demonstrate direct immunoregulatory effects of specific sex steroids on human PBMC and support the idea that these hormones may have a role in the pathogenesis and treatment of some autoimmune disorders.

Adjuvants, Immunologic↗
PubMedDate not supplied

Systemic lupus erythematosus in 49 Israeli males: a retrospective study.

Forty-nine male SLE patients, diagnosed and followed in seven medical centers in Israel between 1954 and 1983, were studied and analyzed retrospectively in order to determine whether the disease in males was clinically different from that reported in females both in Israel and in the world literature. The primary clinical and laboratory manifestations, the severity of the disease at the onset or at any time during the course of the disease, and the 1-15 year survival rates were not different from those described before in female SLE, although neurological involvement, nephritis, thrombocytopenia, vasculitis and hepatosplenomegaly were more prevalent in our series. However, more than half of the male patients (53%) had a benign course of disease characterized by long remissions requiring minimal or no medication. Long-term remission of serious renal involvement was observed completely in 14 and partially in 5 out of 33 patients. These results suggest that the male sex might alter the clinical course of SLE.

Adolescent↗