Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen,but not by the LACK antigen,are protective against experimental Leishmania (Leishmania) amazonensis infection

Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-gamma) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-gamma and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-gamma and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis.     

Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance

Background

Deterioration of quality of life in the long term has been suggested for celiac disease patients on a gluten-free diet.

Aims

To determine long-term quality of life of celiac disease patients and to assess the benefits of gluten-free diet compliance.

Patients

We prospectively evaluated 53 newly diagnosed adult celiac disease patients.

Methods

The Short Form 36 Health Survey, the Gastrointestinal Symptoms Rating Scale and the Beck Depression Inventory were employed at the time of diagnosis, 1 year, and beyond 4 years (median: 53 months) on treatment.

Results

At 1 year, a significant improvement from baseline in quality of life indicators was observed (p < 0.001 to p < 0.0001) with comparable scores to healthy subjects. At 4 years, the Short Form 36 Health Survey scores (p < 0.002 to p < 0.0002) and Beck Depression Inventory score (p < 0.002) show significant deterioration compare with 1 year. Most scores remained significantly better than those at diagnosis (p < 0.03 to p < 0.0005). No changes were detected in the Gastrointestinal Symptoms Rating Scale scores. The long-term impairment of quality of life was attributable to the deterioration of most dimensions in patients who were not strictly compliant with the gluten-free diet (p < 0.05 to p < 0.001).

Conclusions

Long-term deterioration of quality of life outcomes after the first year of gluten-free diet was associated with the lack of strict compliance with the diet.     

Hepatitis B Screening and Vaccination Practices in Asian American Primary Care

Background/Aims

Screening for hepatitis B virus (HBV) is recommended in populations with anticipated prevalence ≥2%. This study surveyed HBV screening and vaccination practices of Asian American primary care providers (PCPs).

Methods

Approximately 15,000 PCPs with Asian surnames in the New York, Los Angeles, San Francisco, Houston, and Chicago areas were invited to participate in a web-based survey. Asian American PCPs with ≥25% Asian patients in their practice were eligible.

Results

Of 430 (2.9%) survey respondents, 217 completed the survey. Greater than 50% followed ≥200 Asian patients. Although 95% of PCPs claimed to have screened patients for HBV, 41% estimated that ≤25% of their adult Asian patients had ever been screened, and 50% did not routinely screen all Asian patients. In a multivariable analysis, the proportion of Asian patients in the practice, provider geographic origin and the number of liver cancers diagnosed in the preceding 12 months were significantly associated with a higher likelihood of screening for HBV. Over 80% of respondents reported that ≤50% of their adult Asian patients had received the HBV vaccine.

Conclusions

Screening and vaccination for HBV in Asian American patients is inadequate. Measures to improve HBV knowledge and care by primary-care physicians are critically needed.     

Unicompartmental knee arthroplasty: Is robotic technology more accurate than conventional technique?

BackgroundRobotic-assisted unicompartmental knee arthroplasty (UKA) with rigid bone fixation "can significantly improve implant placement and leg alignment. The aim of this cadaveric study was to determine whether the use of robotic systems with dynamic bone tracking would provide more accurate UKA implant positioning compared to the conventional manual technique.MethodsThree-dimensional CT-based preoperative plans were created to determine the desired position and orientation for the tibial and femoral components. For each pair of cadaver knees, UKA was performed using traditional instrumentation on the left side and using a haptic robotic system on the right side. Postoperative CT scans were obtained and 3D-to-3D iterative closest point registration was performed. Implant position and orientation were compared to the preoperative plan.ResultsSurgical RMS errors for femoral component placement were within 1.9 mm and 3.7° in all directions of the planned implant position for the robotic group, while RMS errors for the manual group were within 5.4 mm and 10.2°. Average RMS errors for tibial component placement were within 1.4 mm and 5.0° in all directions for the robotic group; while, for the manual group, RMS errors were within 5.7 mm and 19.2°.ConclusionsUKA was more precise using a semiactive robotic system with dynamic bone tracking technology compared to the manual technique.     

Comparación de 2 estrategias de derivación en el diagnóstico de la espondiloartritis axial en España. Estudio RADAR

ObjectivesImproving referral of patients with back pain to rheumatologists could accelerate the diagnosis of axial spondyloarthritis. The RADAR study compared two strategies in the referral of patients with chronic back pain (> 3 months) with an onset before the age of 45 years from primary care centers to rheumatology departments, in relation to the diagnosis of axial spondyloarthritis.Patients and methodsEach primary care center was assigned a referral strategy for its patients: (a) strategy 1, patients who had one of the 3 following criteria: inflammatory back pain, HLA-B27 positivity or sacroiliitis in imaging; or (b) strategy 2, patients who had 2 of the following 6: inflammatory back pain, HLA-B27 positivity, sacroiliitis in imaging, family history of axial spondyloarthritis, extra-articular manifestations or good response to nonsteroidal antiinflammatory drugs. The rheumatologist established the final diagnosis.ResultsEighty-eight Spanish patients (mean age 36.8 years [SD 8.7], 55.7% females and 44.3% males) were referred for evaluation, 60 patients under strategy 1 and 28 under strategy 2. A definitive diagnosis of axial spondyloarthritis was established in 25.4% with strategy 1 and in 28.6% with strategy 2 (p = NS). Inflammatory back pain was the criterion most commonly used for referral, and the agreement rate between the primary care physician and rheumatologist was 75%.ConclusionsA simple referral strategy based on one of three3 criteria proved as effective as a strategy based on two of 6 criteria in diagnosing axial spondyloarthritis. Inflammatory back pain was the criterion most commonly used for patient referral     

Cross-talk between CD31 and the signaling lymphocytic activation molecule-associated protein during interferon- gamma production against Mycobacterium tuberculosis

Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)- gamma production during tuberculosis by investigating the role of CD31, a receptor that attenuates T cell receptor signals. After antigen stimulation, CD3(+)CD31(+) blood lymphocytes decreased in healthy donors and in tuberculosis patients with robust Th1 responses to Mycobacterium tuberculosis and IFN- gamma was secreted only by CD31(-) T cells. In contrast, in patients with weak Th1 cytokine responses to M. tuberculosis, the level of CD3(+)CD31(+) lymphocytes was increased and IFN- gamma production was low. Furthermore, the inverse relationship between CD31 expression and IFN- gamma production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN- gamma inducer in tuberculosis. Interestingly, CD31 bound to SLAM-associated protein (SAP), an IFN- gamma inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN- gamma response to M. tuberculosis. Thus, CD31, when binding to SAP, interferes with Th1 responses, suggesting that CD31 has a key regulatory role in the signaling pathway(s) leading to the IFN- gamma response to M. tuberculosis.     

New mutations, hotspots, and founder effects in Brazilian patients with steroid 5α-reductase deficiency type 2

Mutations of the steroid 5-reductase type 2 (SRD5A2) gene in 46,XY subjects cause masculinization defects of varying degrees, due to reduced or impaired enzymatic activity. In this study, sequence abnormalities of the SRD5A2 gene were assessed by polymerase chain reaction with specific primers and automated sequencing analysis in DNA samples from 20 patients with suspected steroid 5-reductase type 2 deficiency from 18 Brazilian families. Eleven subjects presented SRD5A2 homozygous single-base mutations (two first cousins and four unrelated patients with G183S, two with R246W, one with del642T, one with G196S, and one with 217_218insC plus the A49T variant in heterozygosis), whereas four were compound heterozygotes (one with Q126R/IVS3+1G>A, one with Q126R/del418T, and two brothers with Q126R/G158R). Three patients were heterozygous for A207D, G196S, and R266W substitutions. The V89L polymorphism was found in heterozygosis in one of them (with A207D) and in one case with an otherwise normal gene sequence. The A49T variant was also detected in heterozygosis in the second case without other sequencing abnormalities. Four patients harbor yet non-described SRD5A2 gene mutations: a single nucleotide deletion (del642T), a G158R amino acid substitution, a splice junction mutation (IVS3+1G>A), and the insertion of a cytosine (217_218insC) occurring at a CCCC motif. This is the first report of a single-nucleotide insertion in the coding sequence of the SRD5A2 gene. In addition to these new mutations, this investigation reveals the prevalence of G183S substitution among a subset of African–Brazilian patients and presents evidences of the recurrence of already known mutations.     

Role of T cell death in maintaining immune tolerance during persistent viral hepatitis

Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate na ve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.