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Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by extensive bone resorption. The mechanisms underlying this matrix loss have not been elucidated. We report here that blood samples from PsA patients, particularly those with bone erosions visible on plain radiographs, exhibit a marked increase in osteoclast precursors (OCPs) compared with those from healthy controls. Moreover, PsA PBMCs readily formed osteoclasts in vitro without exogenous receptor activator of NF-κB ligand (RANKL) or MCSF. Both osteoprotegerin (OPG) and anti-TNF antibodies inhibited osteoclast formation. Additionally, cultured PsA PBMCs spontaneously secreted higher levels of TNF-α than did healthy controls. In vivo, OCP frequency declined substantially in PsA patients following treatment with anti-TNF agents. Immunohistochemical analysis of subchondral bone and synovium revealed RANK-positive perivascular mononuclear cells and osteoclasts in PsA specimens. RANKL expression was dramatically upregulated in the synovial lining layer, while OPG immunostaining was restricted to the endothelium. These results suggest a model for understanding the pathogenesis of aggressive bone erosions in PsA. OCPs arise from TNF-α–activated PBMCs that migrate to the inflamed synovium and subchondral bone, where they are exposed to unopposed RANKL and TNF-α. This leads to osteoclastogenesis at the erosion front and in subchondral bone, resulting in a bidirectional assault on psoriatic bone

The rapid decline in OCPF and overall improvement in BMO after anti-TNFalpha therapy provides one mechanism to explain the anti-erosive effects of TNF blockade in PsA. Persistence of BMO after etanercept treatment, despite a marked clinical response, was unexpected, and suggests ongoing subchondral inflammation or altered remodelling in PsA bone.

This study evaluated the in vitro immune responses to different components of the hepatitis B surface antigen (HBsAg) over the course of acute hepatitis B virus (HBV) infection. Early in the convalescent phase of infection, while HBsAg was present in the serum, peripheral blood mononuclear cells (PBMCs) were stimulated with preS2 peptide or hepatitis B surface protein. Specific IgG directed to different components of HBsAg was produced without a polyclonal increase in total IgG production. Stimulation with preS2 peptide produced IgG to the preS2 peptide (anti-preS2) and to the S antigen (anti-HBs). Hepatitis B surface protein stimulation produced anti-HBs but not anti-preS2. After this initial reactive phase, the PBMCs did not produce specific antibody when stimulated with either component of HBsAg; this effect lasted greater than 1 year. At some time 1-2 years after acute infection, the pattern of in vitro S antigen- and preS2 antigen-stimulated anti-HBs response reemerged in the PBMCs. Reemergence of sustained preS2 peptide-stimulated anti-preS2 response was not observed.

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