Anti-Factor XII monoclonal antibody, clone BIXIII-5156

Hereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mutation in gene F12 (T859A, resulting in p.W268R) which encodes coagulation factor XII (FXII). Functional analysis reveals enhanced autocatalytic cleavage of the mutated protein and spontaneous FXII activation in patient plasma and in supernatant of transfected HEK293 cells expressing recombinant W268R-mutated proteins. Furthermore, we observe reduced plasma pre-kallikrein, cleaved high molecular weight kininogen and elevated plasma bradykinin. Neutrophils are identified as a local source of FXII. Interleukin-1 beta (IL-1 beta) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins. Treatment with icatibant (bradykinin-B2-antagonist) or anakinra (interleukin-1-antagonist) reduces disease activity in patients. In conclusion, our findings provide a link between contact system activation and cytokine-mediated inflammation.

The rate coefficients for the rotational de-excitation of AlO+ by collisions with He are determined. The possible production mechanisms of the AlO+ ion in both diffuse and dense molecular clouds are first discussed. A set of ab initio interaction energies is computed at the CCSD(T)-F12 level of theory, and a three-dimensional analytical model of the potential energy surface is obtained using a linear combination of reproducing kernel Hilbert space polynomials together with an analytical long range potential. The nuclear spin free close-coupling equations are solved and the de-excitation rotational rate coefficients for the lower 15 rotational states of AlO+ are reported. A propensity rule to favour Delta j = -1 transitions is obtained while the hyperfine resolved state-to-state rate coefficients are also discussed.