Search

The human cell surface antigen, CD24, is a glycosyl phosphatidylinositol (GPI)-linked glycoprotein that has been implicated in the differentiation and activation of granulocytes and B lymphocytes. Changes in expression of the antigen occur at critical times during B lineage development. CD24 was cloned by its homology to mouse heat-stable antigen. Southern blot analysis suggested the presence of multiple CD24 related sequences in the human genome. We have now mapped CD24 homologous sequences to chromosomes 6q21, 15q21-q22, and Yq11 by screening a panel of somatic cell hybrid DNAs and by in situ hybridization. At least two additional homologues, one located on chromosome 1 at band p36 and one tentatively mapped to chromosome 20, that are distantly related to CD24 were identified. Southern analysis of male and female DNA samples confirmed the presence of CD24 homologous sequences on the human Y chromosome. Sequencing of DNA fragments amplified from monochromosomal somatic cell hybrids showed that the CD24 cDNA was derived from a transcript originating from a gene on chromosome 6. The CD24 gene on the Y chromosome had many base changes compared to the cDNA but had retained an open reading frame, leaving open the question of whether this gene is functional. Both ATGs in the translation initiation region of CD24 homologous sequences on chromosome 15 were converted to GTGs, making it unlikely that this gene, if functional, encodes a protein similar to CD24. CD24, therefore, is a member of a multigene family, but it remains to be determined whether any of the related genes are functional.

Toxic shock syndrome toxin 1 (TSST-1), an exotoxin produced by many Staphylococcus aureus strains, is implicated as the prime causal agent of toxic shock syndrome (TSS). A sensitive and specific noncompetitive enzyme-linked immunosorbent assay (ELISA) capable of detecting TSST-1 at concentrations from 0.5 to 16 ng/ml was developed. This assay did not detect other staphylococcal enterotoxins including A, B, C1, C2, C3, D, and E. Possible interactions with protein A were readily eliminated by pretreatment of test samples with 10% normal rabbit serum. The assay was adapted for rapid screening of TSST-1 production by S. aureus isolates in culture supernatants in vitro and for detection of TSST-1 in vaginal washings of TSS patients and healthy controls in vivo. All 35 S. aureus isolates confirmed to be TSST positive by Ouchterlony immunodiffusion and 59 of 60 isolates confirmed to be TSST-1 negative gave concordant results by ELISA. Interestingly, toxigenic S. aureus strains isolated from TSS patients quantitatively produced significantly more TSST-1 in vitro compared with toxigenic control strains (P less than 0.05, Mann-Whitney rank sum test). TSST-1 could be detected by ELISA in three of four vaginal washings collected within 3 days of hospitalization from three women with acute menstrual TSS, compared with 0 of 17 washings from nine TSS patients hospitalized longer than 3 days (P = 0.003, Fisher's exact test) and 1 of 15 washings from 14 healthy control women (P = 0.016). This noncompetitive ELISA should be particularly useful for rapid screening of TSST-1 production by S. aureus isolates, for the purification and biochemical characterization of TSST-1, and for human and animal studies of the pathogenesis of TSS.

Toxic shock syndrome toxin-1 (TSST-1) is implicated as the major exotoxin associated with menstrual toxic shock syndrome. The role of TSST-1 in nonmenstrual TSS is less certain. We examined serum IgG responses to TSST-1 in 16 nonmenstrual (9 female, 7 male) and 14 menstrual TSS patients, and in 87 women and 66 men as age-matched healthy controls, using an enzyme-linked immunosorbent assay (ELISA). Relative ELISA titers were expressed as percent activity of a mid level serum standard tested concurrently. Based on 95% confidence estimates for predicting a negative titer (20.6 +/- 8.2%) using sera in which TSST-1 specific IgG was demonstrated to be absent by western blot, 24% of control women and 9% of control men lacked TSST-1 specific IgG in the random survey (p less than 0.05, Fisher's exact test). Relative titers in acute sera of menstrual TSS women (26.2 +/- 5.2%, mean +/- S.E.), but not nonmenstrual TSS women (71.8 +/- 18.6%), were significantly lower than those of control women (78.9 +/- 7.3%, p less than 0.01, Mann-Whitney test). Acute titers from male TSS patients (37.0 +/- 15.6%) were also significantly lower than those in control men (114.6 +/- 11.0% (p less than 0.05). Antibody titers from menstrual TSS women and TSS men remained low during convalescence. Nevertheless, seroconversion to TSST-1 was demonstrated by western blot in 7 of 10 patients in whom TSST-1 positive S. aureus was isolated, but in neither of two patients without toxigenic S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)