Microparticles as biomarkers in autoimmunity: from dust bin to center stage

Microparticles are small membrane-bound vesicles released from activated and dying cells. As shown in a study of primary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis, levels of microparticles in the blood, as measured by a solid-phase prothrombinase assay or flow cytometry, are increased with autoimmunity. Among patients with these conditions, however, particle numbers were inversely related to disease activity and levels of the enzyme secretory phospholipase A2 that can digest membrane lipids and perhaps cause particle loss. These findings suggest microparticles as novel biomarkers for autoimmunity, with levels reflecting events leading to their loss as well as production

Quire: Lightweight Provenance for Smart Phone Operating Systems

Smartphone apps often run with full privileges to access the network and sensitive local resources, making it difficult for remote systems to have any trust in the provenance of network connections they receive. Even within the phone, different apps with different privileges can communicate with one another, allowing one app to trick another into improperly exercising its privileges (a Confused Deputy attack). In Quire, we engineered two new security mechanisms into Android to address these issues. First, we track the call chain of IPCs, allowing an app the choice of operating with the diminished privileges of its callers or to act explicitly on its own behalf. Second, a lightweight signature scheme allows any app to create a signed statement that can be verified anywhere inside the phone. Both of these mechanisms are reflected in network RPCs, allowing remote systems visibility into the state of the phone when an RPC is made. We demonstrate the usefulness of Quire with two example applications. We built an advertising service, running distinctly from the app which wants to display ads, which can validate clicks passed to it from its host. We also built a payment service, allowing an app to issue a request which the payment service validates with the user. An app cannot not forge a payment request by directly connecting to the remote server, nor can the local payment service tamper with the request

Antinuclear antibodies in healthy people: the tip of autoimmunity's iceberg?

Antinuclear antibodies (ANAs) are venerable biomarkers for assessing the diagnosis and prognosis of patients with autoimmunity. While closely associated with diseases such as systemic lupus erythematosus, ANA expression occurs commonly in healthy people. The basis for this expression is unknown, although it may reflect features of the assays for antibody detection or intrinsic immunological disturbances in otherwise normal individuals. Like autoimmunity itself, ANA expression is more common among women than men, pointing to an important determinant of these responses. Future research will clarify the mechanisms of ANA expression and the utility of current assays as antecedent and screening biomarkers

Genetic control of the immune response to staphylococcal nuclease. VII. Role of non-H-2-linked genes in the control of the anti-nuclease antibody response

The role of non-H-2-linked genes in the control of the antibody response to staphylococcal nuclease has been investigated. 3 wk after immunization with nuclease in complete Freund's adjuvant, strain A/J (H-2 a) mice produced significantly higher titers of antibody than strain B10.A (H-2(a)) mice, whereas mice of strains A.BY (H-2(b)) and B10 (H-2(b)) produced barely detectable titers. With hyperimmunization, A/J and A.BY mice reached the same peak levels for antibody titers, both severalfold higher than those reached by B10.A and B10 mice. Analysis of the specificity of antibodies by assessment of binding to two fragments of nuclease showed similarities between strains of the same H-2 haplotype. These results suggest that although H-2-1inked genes determined initial responsiveness at 3 wk and the relative proportions of antibodies directed toward different antigenic determinants on the nuclease molecule, non-H-2-linked genes determined the overall magnitude of the hyperimmuneresponse. Measurement of the affinity of the antibodies to the nuclease fragment (1-126) showed that strains B10 and B10.A produced antibodies with 7- to 10-fold higher affinity than comparable antibodies from strains A.BY and A/J. In a backcross of (B10.A × A/J) × B10.A, the level of antibody segregated independently of the Ig-1(e) C(H) allotype and the A/J anti-nuclease idiotypes. Thus, a gene(s) linked to neither H-2 nor heavy chain structural genes appears to control the aggregate response to antigenic determinants on the nuclease molecule independent of subspecificities of these antibodies or their idiotype

Developments in the scientific understanding of lupus

Systemic lupus erythematosus is a systemic autoimmune disease characterized by the production of antinuclear antibodies (ANAs). Recent research into human and murine lupus suggests that disease susceptibility results from genetic polymorphisms regulating immune responses as well as impairing the clearance of apoptotic cells. Because the products of dead cells, including nucleic acids, have immunologic activity, this situation can promote antigen-driven ANA responses. Furthermore, immune complexes of ANAs can drive the production of proinflammatory cytokines, inducing the 'interferon signature', and intensifying disease. Together, these findings point to new genetic and immunologic markers of disease as well as targets for new therapies