Brief report of complicated Yersinia enterocolitica infection in an immunocompetent host: Review of the literature and pathogenicity mechanisms.

Background: We report a case of a 47-year-old male presenting with Yersinia enterocolitica septicemia with no known risk factors for invasive infection, found to have multiloculated liver and splenic abscesses with an antecedent history of mild enterocolitis. Case presentation: Our patient presented with septic shock in the setting of gastroenteritis with abdominal pain and fever. On work-up, he was found to have multiloculated hepatic and splenic abscesses secondary to Y. enterocolitica. No identifiable risk factors (ie, iron-overload syndrome or immunosuppression) for Y. enterocolitica septicemia were identified in our patient. Our patient was treated with a prolonged course of antibiotics until imaging resolution of his liver and splenic abscesses. Conclusion: Invasive Y. enterocolitica in an immunocompetent host is rare. Our case highlights the pathogenicity of Y. enterocolitica, and important treatment and management considerations.

Historique: Les auteurs rendent compte du cas d'un homme de 47 ans dont le tableau clinique révèle un sepsis à Yersinia enterocolitica sans facteurs de risque connus d'infection invasive, qui présentait des abcès hépatiques et spléniques multiloculés et des antécédents d'entérocolite bénigne. Présentation du cas: Le patient est arrivé en choc septique dans le contexte d'une gastroentérite, de douleurs abdominales et de fièvre. Le bilan a démontré la présence d'abcès hépatiques et spléniques multiloculés consécutifs à l'Y. enterocolitica. Aucun facteur de risque identifiable (syndrome de surcharge en fer ou immunosuppression) de sepsis à Y. enterocolitica n'a été observé. Le patient a reçu une antibiothérapie prolongée jusqu'à la résolution des abcès hépatiques et spléniques confirmée par imagerie. Conclusion: L'Y. enterocolitica invasive est rare chez un hôte immunocompétent. Ce cas fait ressortir la pathogénicité de l'Y. enterocolitica ainsi que des considérations importantes relativement au traitement et à la prise en charge.

The essential role of physician as advocate: how and why we pass it on.

There is consensus amongst regulatory and certifying associations that the role of physician as advocate is a fundamental competency for Canadian physicians. Understanding what advocacy is and looks like in daily practice is integral to achieving this competency. Identifying barriers and exploring how we as physicians acquire the skills of advocacy are discussed. The current state of advocacy in medical education is reviewed as the starting point for exploring how best to foster the skills of physician as advocate.

HIV-1 viral diversity and its implications for viral load testing: review of current platforms.

The 2008 Recommendations for care of the International AIDS Society reaffirmed the importance of both accurate and sensitive viral load assessment, and by necessity, access to viral load assays. HIV-1 viral load testing is considered essential when initiating antiretroviral therapy (ART), when monitoring ART response, and when considering switching ART regimens. The demand for accurate, reproducible, and cost-effective viral load assays is therefore a global issue. Although the North American and Western European experience has historically been with HIV-1 group M subtype B virus, this paradigm is changing rapidly as migrants and refugees from developing countries with non-B subtype infections often now present for care in the developed world, and travelers to developing countries acquire non-B subtype infection abroad and present for care at home. Awareness of any clinical or laboratory differences between the common HIV-1 group M subtype B and the newer HIV-1 strains being seen in practice is therefore increasingly important. This review of current HIV-1 viral load testing is focused on the potential value of a standardized genotype assignment for HIV-1 viral subtypes, regular monitoring of the performance of available commercial HIV viral load assays on emerging non-B HIV subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs), and a discussion of the implications for resource-limited settings.

Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F.

Autoantibodies to the centromere proteins (CENP), which are major constituents of the primary constriction of metaphase chromosomes, were first described in 1980. In those seminal publications and 30 years of research that have followed, a number of CENP have been identified as autoantibody targets in human diseases. Historically, autoantibodies directed to CENP-A, -B and -C have been considered relatively specific biomarkers for limited cutaneous systemic sclerosis (lcSSc) or the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. These autoantibodies, found in up to 40% of SSc sera, can be identified by indirect immunofluorescence (IIF) on a variety of tissue culture cell lines as a discrete speckled staining pattern of both interphase nuclei and metaphase chromatin. Early in the investigation of anti-CENP, it became apparent that some autoantibodies had a similar IIF pattern wherein as cells entered into the cell cycle, speckled staining of the metaphase chromatin could be observed but, unlike conventional CENP staining, interphase nuclei were not stained. Subsequent studies identified one of the targets of these autoantibodies to be CENP-F, a kinesin binding protein essential for completion of the cell cycle. Early clinical studies found that, unlike antibodies to the earlier described CENP, lcSSc rarely expressed anti-CENP-F and approximately 50% of these patients had a malignancy. This review provides a historical perspective of CENP autoantibodies and focuses on an update of the information on CENP-F and their clinical associations.

Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasmic autoantigen GW182.

A novel autoantigen named GW182 was recently identified when the serum from a patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA library. Unique features of the GW182 protein include 39 repeats of glycine (G) and tryptophan (W) residues, binding to a subset of messenger RNA and localization to unique structures within the cytoplasm that were designated GW bodies (GWBs). The goal of the present study was to identify the clinical features of patients with anti-GW182 antibodies and to characterize the B cell anti-GW182 response by defining the epitopes bound by human autoantibodies. The most common clinical diagnosis of patients with anti-GW182 antibodies was Sjögren's syndrome followed by mixed motor/sensory neuropathy, and systemic lupus erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens, respectively. Epitopes bound by the human autoantibodies were mapped to the GW-rich middle part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens.

A panel of monoclonal antibodies to cytoplasmic GW bodies and the mRNA binding protein GW182.

GW182 is a mRNA binding protein characterized by 60 repeats of glycine (G):tryptophan (W) motifs and is localized in cytoplasmic structures referred to as GW bodies (GWBs). Current evidence suggests that this unique protein plays a role in mRNA processing. To enable a more detailed study of GW182 and GWBs in cells and tissues, including their role in mRNA processing, we developed four monoclonal antibodies (MAbs) that bind the human recombinant GW182 protein. These MAbs can be used for Western blot analysis and indirect immunofluorescence (IIF) on cultured cells and tissues. Of special interest, one of the MAbs, 2D6, can be used to identify GW182 and GWBs in formalin-fixed and paraffin-embedded tissues after using an antigen retrieval method (ARM). All the MAbs described in this study immunoprecipitate the GW182 protein. Epitope mapping using overlapping 15-mer peptides representing the full-length GW182 showed that the major antibody-binding domains of these MAbs are distinct. These MAbs are valuable tools for cell biologists and pathologists to study the location and function of the novel GW182 protein in tissue culture cells, as well as cryopreserved or archived tissues.

Autoantibodies to tissue transglutaminase in Sjögren's syndrome and related rheumatic diseases.

OBJECTIVE: Sjögren's syndrome (SS) has been reported in up to 15% of patients with biopsy proven celiac disease (CD). The diagnosis of CD in the setting of SS and other systemic rheumatic diseases can be difficult because they are often associated with a number of gastrointestinal symptoms and diseases. Although the diagnosis of CD is often confirmed by a small bowel biopsy, marker autoantibodies directed against the endomysium of transitional epithelium (EMA) and tissue transglutaminase (tTG) are highly correlated with biopsy-proven disease and serve as a valuable screening test. We used an IgA-anti-tissue transglutaminase antibody (anti-tTG) ELISA to assess the prevalence of anti-tTG in an unselected cohort of patients with SS and other systemic rheumatic diseases. METHODS: Sera from 50 patients with SS, 50 with systemic lupus erythematosus (SLE), 50 with rheumatoid arthritis (RA), 30 with systemic sclerosis (SSc), and 50 healthy controls were tested for autoantibodies to tTG. A comparison group of 40 sera from patients with biopsy-confirmed CD was also included. IgA anti-tTG was measured by a commercially available ELISA kit (Inova, San Diego, CA) that employs purified tTG. RESULTS: Six of the 50 (12%) IgA sufficient SS patients had anti-tTG compared to 2 (4%) normal sera, 3 (6%) SLE, 2 (7%) SSc, and 1 (2%) RA. By comparison, in the CD cohort, 33 (83%) had anti-tTG. Five of 6 SS patients with anti-tTG had symptoms, signs, or small bowel biopsy findings consistent with a diagnosis of CD. IgA anti-tTG and EMA were accompanied by other IgA autoantibodies in SS sera. CONCLUSION: Anti-tTG ELISA is a reliable method to indicate a coexisting diagnosis of CD in patients with SS. Interestingly, the frequency of false positive tTG tests in any of the systemic rheumatic diseases is not significantly greater than in controls. Further, our study shows that anti-tTG is more prevalent in SS than in other systemic rheumatic diseases. The tTG ELISA may be used as a screening test to identify patients with SS who are at risk and require further evaluation for the presence of CD.