No abstract

Objective. An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor ␣ (TNF␣)-neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model.Methods. Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6-8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF-neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55-TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison.Results. Administration of TNF-neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin-12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria-induced interferon-␥ production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes.

No abstract

Background Genotyping for red blood cell (RBC), platelet and granulocyte antigens is a new tool for clinical pathology, transfusion medicine services and blood banks. Proficiency in laboratory tests can be established by external quality assessments (EQAs), which are required for clinical application in many health care systems. There are few EQAs for molecular immunohematology. Methods We analyzed the participation and pass rates in an EQA for RBC, platelet and granulocyte antigens. This EQA was distributed by INSTAND, a large non-profit provider of proficiency tests, twice per year since fall 2006 as EQA no. 235 Immunohematology A (molecular diagnostic). The coordinators defined at the outset which alleles are mandatory for detection. Results The number of participants steadily increased from 51 to 73 per proficiency by fall 2012. More than 60 institutions utilized this EQA at least once a year. Approximately 80% of them participated in RBC, 68% in platelet and 22% in granulocyte systems. With the exceptions of RHD (82%) and granulocytes (85%), pass rates exceeded 93%. While the pass rate increased for granulocyte and decreased for the ABO system, the pass rates for the other systems changed little over 6 ½ years. Conclusions The INSTAND proficiency test program was regularly used for EQA by many institutions, particularly in Central Europe. While the technical standards and pass rates in the participating laboratories were high, there has been little improvement in pass rates since 2006.