Innate and humoral recognition of the products of cell death: differential antigenicity and immunogenicity in lupus.

While apoptotic debris is believed to constitute the original antigenic insult in lupus (which is characterized by a time-dependent diversification of autoreactivity), whether such debris and autoantibodies specifically recognizing its constituents mediate differential effects on innate and humoral responses in lupus-prone mice is currently unknown. Apoptotic blebs (as opposed to cellular lysate) enhanced preferentially the maturation of dendritic cells (DCs) from bone marrow precursors drawn from lupus-prone mice. Murine, somatically mutated, apoptotic cell-reactive immunoglobulin (Ig)G monoclonal antibodies demonstrated enhanced recognition of DCs and also displayed a prominent lupus strain-specific bias in mediating DC maturation. Further, immunization of such antibodies specifically in lupus-prone mice resulted in widespread humoral autoreactivity; hypergammaglobulinaemia (a hallmark of systemic autoimmunity) was observed, accompanied by enhanced antibody titres to cellular moieties. Induced antibodies recognized antigens distinct from those recognized by the antibodies employed for immunization; in particular, nephritis-associated anti-double stranded (ds) DNA antibodies and neonatal lupus-associated anti-Ro60 antibodies were elicited by a non-dsDNA, non-Ro60 reactive antibody, and Sm was a favoured target. Further, only in lupus-prone mice did such immunization enhance the kinetics of humoral anti-self responses, resulting in the advanced onset of glomerulosclerosis. These studies reveal that preferential innate and humoral recognition of the products of cell death in a lupus milieu influence the indices associated with autoimmune pathology.

Superiority of acridine orange-stained buffy coat smears for diagnosis of partially treated neonatal septicemia.

Early diagnosis of neonatal septicemia is a vexing problem because of its non-specific clinical picture. Many of the neonates with septicemia reaching a referral centre have already been exposed to antibiotics and their blood cultures are often sterile. Scarcity of studies evaluating acridine orange-stained buffy coat smears in detecting neonatal septicemia after administration of antibiotics prompted us to undertake this study. The population studied consisted of 34 cases of neonatal septicemia with positive blood cultures and/or positive buffy coat smears (of these 25 had a positive blood culture) and 25 neonates with a clinical course not suggestive of any infection. Venous blood was drawn for culture, preparation of buffy coat smears, blood counts and micro ESR. The culture and smears were repeated after administration of antibiotics for 48-72 h. Acridine orange stain was the most sensitive test and was significantly more sensitive than Gram's stain (p < 0.005). After the administration of antibiotics, acridine orange was significantly more sensitive than Gram's stain and blood culture (p < 0.05).