Anti-hTNF-α VNAR constructs, D1-BA11-C4 and D1-Fc-C4 (Quad-XTM) which are potent (low pM) in vitro neutralizers of hTNF-α (24) were tested in the Tg197 transgenic human TNF-α model of polyarthritis, in which mice constitutively produce the pro-inflammatory human TNF-α cytokine, and consequently develop spontaneous arthritis. Here, TNF is linked to Arthritis.