Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy.

PURPOSE: To determine associations between polymorphic genes that encode KIRs and their HLA class I ligands in patients with HLA-B27-associated acute anterior uveitis (AAU), with and without axial spondyloarthropathy (axial SpA). METHODS: Molecular DNA typing methods were used to define the frequencies of variable KIR genes and their relevant HLA class I ligands in HLA-B27(+) (B27(+)) Caucasian subjects with AAU and 429 healthy Caucasian control subjects. The patients were evaluated for axial SpA based on their histories using published criteria. RESULTS: Of 143 Caucasian subjects with AAU, 71 (49.6%) had features of axial SpA. The only difference between cases and controls in KIR gene frequencies was a trend toward fewer activating KIRs in subjects with AAU with axial SpA, which reached statistical significance for 2DS5 (P = 0.025, corrected P [P(c)] = 0.05; odds ratio [OR], 0.48; 95% CI, 0.25-0.90). The 3DL1+Bw4(T80) combination implicated in weak inhibition was more frequent in subjects with AAU than in control subjects (P = 2.73 x 10(-28), P(c) = 8.2 x 10(-27); OR, 13.5; 95% CI, 7.73-23.68). The 2DL1+HLA-C2 combination was decreased in subjects with axial SpA compared with subjects with AAU without axial SpA (P = 0.022; P(c) = NS; OR, 0.43; 95% CI, 0.21-0.88). CONCLUSIONS: Evidence was found of a role for KIR-HLA combinations that trigger weaker inhibition in subjects with AAU. Furthermore, there was a trend toward fewer KIR3DS1, -2DS1, and -2DS5 in AAU patients with axial SpA, which have been implicated in NK cell activation. HLA-B27(+) without KIR2DS3 (and -2DS1 and -3DS1) may fail to trigger an early NK cell response to clear antigenic stimuli, which may in part contribute to disease pathogenesis.

Efficacy, safety, and tolerability of abatacept in the management of rheumatoid arthritis.

The management of rheumatoid arthritis (RA) has undergone an impressive transformation over the past few decades. Further understanding of the pathophysiology of the disease process has resulted in the development of biologic agents that target proinflammatory cytokines and both B and T lymphocytes. By blocking an important costimulatory pathway, abatacept leads to a dramatic reduction in T cell stimulation and proliferation. Multiple clinical trials have revealed consistent benefit with regards to clinical and radiographic efficacy, quality of life, and disability in patients suffering from RA who have had inadequate responses to methotrexate or tumor necrosis factor inhibitors. The possibility of remission when used early in the disease course has also been demonstrated. Importantly, abatacept has been very well tolerated with a low rate of serious infections and no apparent increase in malignancies to date. Continued surveillance of the benefits and risks will help to better define its place amongst the other biologic agents in the treatment of RA.

Rheumatoid arthritis: strategies in the management of patients showing an inadequate response to TNFalpha antagonists.

The introduction of medications that target specific proinflammatory cytokines has revolutionized the management of patients with rheumatoid arthritis. The agents that antagonize the effects of tumour necrosis factor (TNF)-alpha -- infliximab, etanercept and adalimumab -- have consistently shown very good efficacy for controlling the clinical and radiographic manifestations of the disease. However, it has become apparent that some patients will receive no clinical benefit, gradually lose the effect over time or experience adverse effects with the TNFalpha antagonists. The management of these patients is challenging and there are no clear guidelines. The concomitant administration of a disease-modifying antirheumatic drug, such as methotrexate, has been shown to improve outcomes. Optimization of the methotrexate or TNFalpha antagonist dose may lead to improved responses, as demonstrated in some dose escalation studies. Switching to another TNFalpha antagonist is a step that is supported by small, mostly uncontrolled studies. Finally, the T-cell co-stimulation antagonist abatacept, as well as the B-cell depleting agent rituximab, are also available for use in patients who have had an inadequate response or intolerance to the TNFalpha antagonists.Genotypic studies have identified TNF and TNF receptor polymorphisms that appear to predict independently whether a patient will respond to a TNFalpha antagonist, but genotyping is not available for routine use in clinical practice. Until such tools for predicting response are widely available, the management of patients with poor responses to TNFalpha antagonists will have to depend upon the wishes of the patient regarding medication dosage schedules and adverse effect profiles, as well as how comfortable the treating physician is with the available biological medications. In this article, we review the current data and construct an algorithm to help guide clinicians in the management of patients with inadequate responses to the TNFalpha antagonists.

Orbital inflammatory disease.

OBJECTIVES: To familiarize rheumatologists and internists with the signs, symptoms, and management of orbital inflammatory disease (OID). METHODS: A comprehensive literature review related to OID was performed and reported from the perspectives of rheumatology, ophthalmology, and radiology. RESULTS: OID is a general term encompassing inflammatory diseases that affect some or all of the structures contained within the orbit external to the globe. Orbital involvement as a part of the initial symptom complex is not uncommon for systemic diseases such as Graves' disease, Wegener's granulomatosis, and sarcoidosis. The management of these and other causes of OID, such as idiopathic orbital inflammation (formerly known as "orbital pseudotumor"), orbital myositis, and Tolosa-Hunt syndrome frequently involves systemic immunosuppression. Before immunosuppression is considered, however, infectious and malignant causes of inflammation must be ruled out. DISCUSSION: Rheumatologists should be familiar with the differential diagnosis of OID and often need to assist colleagues in ophthalmology and internal medicine with the management of this group of diseases.