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New on Antibodies: Interfering With Biologics, Defining Juvenile Myopathies

New on Antibodies: Interfering With Biologics, Defining Juvenile Myopathies

Last week's articles on rheumatology topics in the major nonspecialty journals

TNF Inhibitors

Immunogenicity of Monoclonal Antibodies Against Tumor Necrosis Factor Used in Chronic Immune-Mediated Inflammatory Conditions: Systematic Review and Meta-analysis
JAMA Intern Med Online first, June 24, 2013. Full text $30

This meta-analysis examined 60 references on antibodies against biological therapies (AABs) in patients with autoimmune diseases treated with biological agents. The development of antibodies against the monoclonal antibodies that target tumor necrosis factor (TNF) confers two risks: (1) treatment discontinuation, in rheumatoid arthritis (RA) and (2) hypersensitivity reactions, in all immune-mediated inflammatory diseases (IIMDs). AABs reduce drug concentration and efficacy, possibly through clearance of the drug. Using anti-TNF monoclonal antibodies together with DMARDs reduces the development of antibodies against them and the attendant risks. In contrast to monoclonal antibodies, the incidence of antibodies against entanercept is low, and the AABs are not neutralizing. A significant amount of information is available about this problem in RA and inflammatory bowel disease, but it is scarce for other IIMDs.


Juvenile Idiopathic Inflammatory Myopathies

The Myositis Autoantibody Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies
Medicine, July 2013, Full text $49

In this study,  juvenile idiopathic inflammatory myopathies (JIIM) were characterized by distinct autoantibody phenotypes defined by clinical and demographic characteristics, laboratory features, and outcomes. Of 430 patients in a registry study with serum myositis autoantibodies, 374 had either a single specific myositis-specific autoantibody (MSA) or no identified MSA.

•   Anti-p155/140 autoantibodies were most frequent, in patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM. Their characteristics included Gottron papules, malar rash, “shawl-sign” rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course.
•   Anti-MJ autoantibodies were seen in 20% of JIIM patients, primarily in JDM. They were characterized by muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. 

Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in 10% of JIIM patients.

•   Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and “mechanic’s hands,” and had an older age at diagnosis.
•   The anti-SRP group (exclusively juvenile polymyositis) was characterized by high frequencies of black ethnicity, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use.
•   The anti-Mi-2 subgroup was characterized by Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality.


Contaminated Injections

Review Article: Current Concepts: Fungal Infections Associated with Contaminated Methylprednisolone Injections
N Engl J Med, June 27, 2013. Full text $15

Fungal Infections Associated with Contaminated Methylprednisolone Injections
Now@NEJM, June 28th, 2013. Free full text

More revelations this week about last year's outbreak of fungal infections associated with contaminated methylprednisolone. Unlike the index case, which was reported to be Aspergillus fumigatus, all the other 700-plus cases were determined to be Exserohilum rostratum, a plant pathogen that rarely causes human disease. The first cases presented with meningitis, while later cases presented with back pain caused by epidural abscess, diskitis or vertebral osteomyelitis at the injection site. Some centers are screening by MRI all patients who have received an injection from a contaminated lot. Current recommendations are for voriconazole, with liposomal amphotericin B for severe cases, although therapeutic levels and toxic effects must be managed.


Salt and Autoimmunity

Clinical Implications of Basic Research: A Salty Taste to Autoimmunity
N Engl J Med, June 27, 2013. Full text $15

Increases in the concentrations of sodium chloride enhanced Type 17 helper T cells (Th17) in vitro and in mouse models. Lymphoid tissues need high salt conditions for optimal adaptive immune response during infection. In contrast, a low sodium concentration in blood may protect against systemic Th17-driven inflammation. Hypertonic salt travels to the Th17 nucleus and activates the kinase SGK1, which stabilizes messenger RNA of the interleukin-23 receptor and reinforces the Th17 phenotype. In mouse experiments, high concentrations of salt induce a more severe experimental autoimmune encephalomyelitis. Humans are not big mice, and there is no evidence supporting a similar effect on human autoimmunity. However, hypertonic saline does decrease the incidence of postoperative infection and improves survival after major spinal procedures.

 

 
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