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The diagnosis, treatment, and monitoring of the primary systemic vasculitides associated with circulating antineutrophil cytoplasm autoantibodies (ANCA) have formed the focus of a multicenter collaborative study. Consensus has been reached on criteria for classification, clinical subgroupings by extent and severity of disease, and ''standard'' and ''best alternative'' therapeutic regimens. Two series of randomized controlled trials have been designed; their aims are (1) to harmonize current approaches to treatment and (2) to test the value of newer therapeutic agents, In support of these trials, semiobjective scoring systems have been created and validated, and previous standardization of ANCA serologic and histologic analysis has been adopted. The systems of classification and clinical management described herein represent the recommendations of a multidisciplinary study group that hopes to improve the outcome of patients with primary systemic vasculitis by wide dissemination of the collective experience from interested centers.

NK lymphocytes participate in both innate and adaptive immunity by their prompt secretion of cytokines including IFN-γ, which activates macrophages, and by their ability to lyse virally infected cells and tumor cells without prior sensitization. Although these characteristics of NK cells are well documented, little is known about the genetic program that orchestrates NK development or about the signaling pathways that trigger NK effector functions. By crossing NK-deficient common γ-chain (γc) and recombinase activating gene (RAG)-2 mutant mice, we have generated a novel alymphoid (B−, T−, and NK−) mouse strain (RAG2/γc) suitable for NK complementation in vivo. The role of the c-abl proto-oncogene in murine NK cell differentiation has been addressed in hemopoietic chimeras generated using RAG2/γc mice reconstituted with c-abl−/− fetal liver cells. The phenotypically mature NK cells that developed in the absence of c-abl were capable of lysing tumor targets, recognizing “missing self,” and performing Ab-dependent cellular cytotoxicity. Taken together, these results exclude any essential role for c-abl in murine NK cell differentiation in vivo. The RAG2/γc model thereby provides a novel approach to establish a genetic map of NK cell development.