There remains considerable interest in the possibilities of primary vasculitic syndromes caused in some fashion by infection. With the exception of a few well sustained associations - for example hepatitis B or C with known vasculitic syndromes - most of the purported links between microbial agents and primary vasculitides remain speculative.

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Background-Both matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) have been postulated to play roles in the pathophysiology of giant cell arteritis (GCA) because of their ability to degrade elastin. Understanding the specific mediators of arterial damage in GCA could lead to new therapeutic targets in this disease. Methods and Results-Temporal artery biopsy specimens were obtained from 147 consecutive patients suspected of GCA. Clinical and histopathological data were collected according to protocol. Using immunohistochemistry, we compared the expression of MMP-2 and MMP-9 in the temporal artery biopsies of both GCA cases (nϭ50) and controls (nϭ97). MMP-9 was found more frequently in positive than in negative temporal artery biopsies (adjusted odds ratio [OR], 3.20; Pϭ0.01). In contrast, the frequency of MMP-2 was not significantly different between positive and negative biopsies (adjusted OR, 2.18; Pϭ0.22). Both MMP-2 and MMP-9 were found in macrophages and giant cells near the internal elastic lamina and in smooth muscle cells and myofibroblasts of the media and intima. MMP-9 was also found in the vasa vasorum. MMP-9 but not MMP-2 was associated with internal elastic lamina degeneration, intimal hyperplasia, and luminal narrowing, even after adjustment for possible confounding variables. Conclusions-MMP-9 appears more likely than MMP-2 to be involved in the pathophysiology of GCA. MMP-9 not only participates in the degradation of elastic tissue but also is associated with intimal hyperplasia, subsequent luminal narrowing, and neoangiogenesis.

Blood monocytes from children with systemic lupus erythematosus (SLE) behave like dendritic cells (DCs), and SLE serum induces healthy monocytes to differentiate into DCs in a type I Interferon (IFN)-dependent manner. Here, we found that these monocytes display significant transcriptional changes, including a prominent IFN signature, compared to healthy controls. Few of those changes, however, explain DC function. Exposure to allogeneic T cells in vitro reprograms SLE monocytes to acquire DC phenotype and function, and this correlates with both IFN-inducible (IP10) and pro-inflammatory cytokine (IL1b and IL6) expression. Furthermore, we found that both IFN and SLE serum induce the upregulation of CCR7 transcription in these cells. CCR7 protein expression requires however a second signal provided by TLR agonists such as LPS. Thus, SLE serum “primes” a subset of monocytes to readily (<24h) respond to TLR agonists and acquire migratory DC properties. Our findings might explain how microbial infections exacerbate lupus.