A Case of Granuloma Annulare Associated with Secukinumab Use

Granuloma annulare (GA) is a benign inflammatory dermatosis characterized clinically by dermal papules and annular plaques. The pathogenesis of GA is not well understood, although it is thought to result from a delayed-type hypersensitivity reaction in which inflammatory cells elicit connective tissue degradation. This condition has been seen following the use of several drugs, including tumor necrosis factor-alpha (TNF-α) inhibitors, which paradoxically have also been reported to treat GA. We report the case of a patient who developed GA in association with secukinumab, an interleukin-17A antagonist, and discuss its implications for our understanding of the pathogenesis of GA.

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens. Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts. Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining (basal lamina). The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa. The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa.

Metalloproteinases in degenerative aortic disease

1. Atherosclerosis and aneurysm of the abdominal aorta are associated with thinning of the medial connective tissue. We have investigated the presence of the connective-tissue-degrading metalloproteinases in homogenates prepared from atherosclerotic, aneurysmal and control aortic media. 2. Gelatinase activity was much increased in homogenates from atherosclerotic and aneurysmal aorta [10.911.8 and 13.3 ± 3.3 μg of gelatin hydrolysed h−1 (mg of protein)−1 respectively]. This gelatinase activity was highest at the luminal aspect of the aortic media, where the activity increased three-to five-fold after the destruction of α2-macroglobulin. Zymograms demonstrated the principal gelatinase in atherosclerotic aorta to have a molecular mass of about 92 kDa, whereas in aneurysmal aorta there was a spectrum of gelatinase activity from 92 to 55 kDa. 3. Collagenase and stromelysin (proteoglycanase) could be detected by immunoblotting in homogenates of aneurysmal aorta, but rarely in atherosclerotic aorta and never in control aorta. Collagenase and stromelysin activities were low, but increased two-to three-fold after the destruction of tissue inhibitor of metalloproteinases. Collagenase and stromelysin activities were highest at the adventitial aspect of aneurysmal media. 4. The secretion of gelatinase by inflammatory cells at the intima of diseased aorta could have a pathological role in establishing atherosclerotic plaques and medial thinning. Secretion of collagenase, gelatinase and stromelysin from the adventitia could accelerate connective tissue degradation in the media of aneurysmal aorta.