Priapism after tumor necrosis factor alpha inhibitor use.

We present a possible important association of tumor necrosis factor-alpha inhibition (TNFa-i) and erectile function in a male patient with rheumatoid arthritis (RA). Long-standing, untreated RA may result in significant physical limitation and disability, however often overlooked is the association between RA and erectile and sexual dysfunction. Ischemic priapism is currently unrecognized as an adverse reaction associated with TNFa-i use and there have been no reported cases with adalimumab. Our patient, a 58-year-old Hispanic man, with sero-positive, erosive RA developed persistent priapism (17 days) despite multiple urologic interventions after initial adalimumab 40 mg administration. TNFa has recently been implicated as a potential factor in erectile dysfunction through its role in vascular reactivity. Excess TNFa, from active RA, may perturb intracavernosal smooth muscle and endothelial cell function; theoretically, TNFa inhibition may then causes excess local nitric oxide production and subsequent priapism. The potential role of TNFa-i in ED and risk for priapism is an important area for future study.

Evolution of classification criteria for rheumatoid arthritis: how do the 2010 criteria perform?

Classification criteria are created in an attempt to produce a homogenous group of subjects with rheumatoid arthritis (RA) who can be used for clinical and basic research. The 1987 revised criteria lead to improved performance and more confidence in correct classification compared with the 1958 criteria. As therapies were introduced and early, aggressive approaches to RA management became common, there was a growing need for clinical trials focusing on early RA. The 2010 criteria were created to facilitate study of subjects at earlier stages in the disease. This article reviews the diagnostic performance of the 2010 criteria.

Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus.

Engagement of the low-affinity Ab receptor FcγRIIb downregulates B cell activation, and its dysfunction is associated with autoimmunity in mice and humans. We engineered the Fc domain of an anti-human CD19 Ab to bind FcγRIIb with high affinity, promoting the coengagement of FcγRIIb with the BCR complex. This Ab (XmAb5871) stimulated phosphorylation of the ITIM of FcγRIIb and suppressed BCR-induced calcium mobilization, proliferation, and costimulatory molecule expression of human B cells from healthy volunteers and systemic lupus erythematosus (SLE) patients, as well as B cell proliferation induced by LPS, IL-4, or BAFF. XmAb5871 suppressed humoral immunity against tetanus toxoid and reduced serum IgM, IgG, and IgE levels in SCID mice engrafted with SLE or healthy human PBMC. XmAb5871 treatment also increased survival of mice engrafted with PBMC from a unique SLE patient. Unlike anti-CD20 Ab, coengagement of FcγRIIb and BCR complex did not promote B cell depletion in human PBMC cultures or in mice. Thus, amplification of the FcγRIIb inhibitory pathway in activated B cells may represent a novel B cell-targeted immunosuppressive therapeutic approach for SLE and other autoimmune diseases that should avoid the complications associated with B cell depletion.