Dental metal-induced innate reactivity in keratinocytes

Gold, nickel, copper and mercury, i.e. four metals frequently used in dental applications, were explored for their capacity to induce innate immune activation in keratinocytes (KC). Due to their anatomical location the latter epithelial cells are key in primary local irritative responses of skin and mucosa. Fresh foreskin-derived keratinocytes and skin and gingiva KC cell lines were studied for IL-8 release as a most sensitive parameter for NF-kB activation. First, we verified that viral-defense mediating TLR3 is a key innate immune receptor in both skin- and mucosa derived keratinocytes. Second, we found that, in line with our earlier finding that ionized gold can mimic viral dsRNA in triggering TLR3, gold is very effective in KC activation. It would appear that epithelial TLR3 can play a key role in both skin- and mucosa localized irritation reactivities to gold. Subsequently we found that not only gold, but also nickel, copper and mercury salts can activate innate immune reactivity in keratinocytes, although the pathways involved remain unclear. Although current alloys have been optimized for minimal leakage of metal ions, secondary factors such as mechanical friction and acidity may still facilitate such leakage. Subsequently, these metal ions may create local irritation, itching and swelling by triggering innate immune reactions, potentially also facilitating the development of metal specific adaptive immunity

Serum autoantibodies directed against transglutaminase-2 have a low avidity compared with alloantibodies against gliadin in coeliac disease

Pathophysiology and treatment of rheumatic disease

Sodium tetrachloropalladate for diagnosing palladium sensitization

Background. Exposure to palladium (Pd) may lead to clinical allergic reactions. With frequent nickel (Ni) exposure and cross-reactivity between Ni and Pd at the T cell recognition level, positive Pd reactions on patch testing are surprisingly uncommon. PdCl2 is often used for epicutaneous patch testing. Objectives. To compare the sensitivity and specificity of sodium tetrachloropalladate (Na2PdCl4) and PdCl2 for Pd patch testing in metal-allergic patients and non-allergic controls. Methods. Twenty-six metal-allergic patients and 26 non-allergic controls were selected on the basis of detailed medical histories. Patch test results were used to determine the diagnostic performance of the two Pd salts as compared with NiSO4. Results. With three outliers in both groups, the sensitivity/specificity were calculated to be 42%/96% for PdCl2, 65%/92% for Na2PdCl4, and 77%/92% for NiSO4. Furthermore, of all (n = 19) Na2PdCl4 reactors, 17 (89%) also showed positive reactions to NiSO4. Conversely, of all (n = 22) NiSO4 reactors, 17 (77%) showed concomitant positive reactions to Na2PdCl4. Conclusions. Positive test reactions to Na2PdCl4 are confirmed by large-scale concordant reactions to PdCl2 and NiSO4. Although statistical significance was not reached, the increased sensitivity has important clinical relevance, as false-positive results are rare. Incorporation of Na2PdCl4 into standard and/or dental screening patch test series is suggested

Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators

Background Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll-like receptor (TLR)-4. Objectives Here, we studied an extended panel of transition metals neighbouring nickel in the periodic table of elements, for their capacity to activate human monocyte-derived dendritic cells (MoDCs). Methods The panel included chromium, cobalt, and palladium, all of which are known to be frequent clinical sensitizers. MoDC activation was monitored by assessment of release of the pro-inflammatory mediator interleukin (IL)-8, a major downstream result of TLR ligation. Results The data obtained in the present study show that cobalt and palladium also have potent MoDC-activating capacities, whereas copper and zinc, but not iron and chromium, have low but distinct MoDC-activating potential. Involvement of endotoxin contamination in MoDC activation was excluded by Limulus assays and consistent stimulation in the presence of polymyxin B. The critical role of TLR4 in nickel-induced, cobalt-induced and palladium-induced activation was confirmed by essentially similar stimulatory patterns obtained in an HEK293 TLR4/MD2 transfectant cell line. Conclusions Given the adjuvant role of costimulatory danger signals, the development of contact allergies to the stimulatory metals may be facilitated by signals from direct TLR4 ligation, whereas other metal sensitizers, such as chromium, may rather depend on microbial or tissue-derived cofactors to induce clinical sensitization