Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage

Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate (r=0.40; p<0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B.This study confirms cutaneous PDC infiltration as hallmark of LE. The topographical segregation in D-PDC and J-PDC suggests a novel view of the role of these cells in skin autoimmunity.     

Leg Amputation for an Extensive,Severe and Intractable Sickle Cell Anemia Ulcer in a Brazilian Patient

A 35-year-old African Brazilian patient had sickle cell anemia complicated with recurrent vasoocclusive (VOC) crises and refractory painful leg ulcers for 16 years. The ulcers started over both medial malleoli and expanded gradually. The ulcer on the left leg spread from the foot to the knee circumferentially and was refractory to all forms of therapy within the frame work of multi-disciplinary care. The patient agreed to a below the knee amputation of the left leg. He felt much better after the amputation but developed severe neuropathic phantom pain that was well controlled medically. He could differentiate the sickle cell anemia and ulcer pain from the neuropathic pain. About 6 months after the amputation he had dengue fever with fatal outcome. This is the first report of treatment of refractory sickle cell anemia leg ulcer with amputation and probably the first report of a Brazilian patient with sickle cell anemia and dengue fever.     

Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen (HBsAg) in the serum

BackgroundHepatitis B surface antigen (HBsAg) clearance during chronic hepatitis B (CHB) infection is associated with improved long-term clinical outcome, so is considered an important therapeutic goal in CHB. Studies have shown that serum HBsAg quantification during, and at end of, treatment may predict long-term HBsAg loss.ObjectivesPerformance comparison of the qualitative Elecsys HBsAg II assay using a quantitative research protocol and an established quantitative HBsAg assay.Study designA dilution algorithm was developed for the Elecsys HBsAg II assay to allow quantification of HBsAg levels; this was used to measure HBsAg levels in a range of samples including sera from patients infected with different HBV genotypes, HBV mutants, and longitudinal samples from patients undergoing antiviral treatment. Results were compared with those from the quantitative Architect HBsAg assay.ResultsThere was significant overall correlation between Elecsys and Architect assays (correlation coefficient [r] = 0.97; p < 0.001). HBsAg levels measured with both assays correlated well in all phases of infection (r = 0.80–0.96), across all genotypes tested (HBV genotype A, r = 0.89; HBV genotype D, r = 0.97), and in samples with lamivudine-resistant mutations (r = 0.94). Bland–Altman analysis showed only minor discordance between assays in different phases of chronic HBV-infection (3.8–5.1%). This strong correlation was also present for sera with lower HBsAg concentrations. On-treatment HBsAg levels were similar when measured with either assay.ConclusionsUsing a simple dilution algorithm, the quantitative Elecsys HBsAg II assay reliably determined serum HBsAg levels in a wide range of samples, and showed very high correlation with the Architect HBsAg assay.     

Interleukin-12 primes CD4+ T cells for interferon-γ production and protective immunity during Mycobacterium avium infection

Interleukin-12 (IL-12) is a crucial cytokine for the generation of a protective immune response against Mycobacterium avium infection. In contrast to infected control mice, IL-12-deficient mice were unable to control bacterial proliferation and their spleen T cells were almost unresponsive in vitro to specific antigens of M. avium. Susceptibility of mice deficient in IL-12 was similar to that of interferon-gamma (IFN-gamma)-deficient mice. These data indicate a crucial role of IL-12 in the development of a T-cell population able to produce IFN-gamma and to mediate protection against M. avium infection. Treatment of M. avium-infected mice with IL-12 induced CD4+ T cells with enhanced capacity to produce IFN-gamma as well as to confer increased protection against M. avium.     

Distribution of Mycoplasma haemofelis in blood and tissues following experimental infection

The aim of the study was to describe blood and tissue copy number distribution during Mycoplasma haemofelis infection and determine if sequestration of organisms in body tissues could explain blood copy number cycling in infected cats. Thirteen domestic–shorthaired cats were used. Blood samples were regularly collected, and at a differing time point post-infection for each cat, tissue samples also collected, for quantitative PCR (qPCR). Absolute haemoplasma copy numbers were calculated for all blood and tissue samples, as well as an estimation of the ratio of tissue haemoplasma copy number to that expected in the tissue if a positive qPCR result arose due to tissue blood supply alone. Cats with high or moderate M. haemofelis blood copy numbers at the time of tissue collection had fewer M. haemofelis copies in most tissues than expected due to the tissue blood supply alone; only splenic and lung tissues consistently contained more M. haemofelis. However tissues collected from cats at a time of very low M. haemofelis blood copy numbers, when putative copy number cycling nadirs were occurring, were usually qPCR negative. Hence no evidence of significant tissue M. haemofelis sequestration was found in this study to explain the copy number cycling reported with this feline haemoplasma species.     

Usefulness of the vibration perception thresholds measurement as a diagnostic method for diabetic peripheral neuropathy: Results from the Rio de Janeiro type 2 diabetes cohort study

Aims

To investigate the associated factors with the vibration threshold perception (VPT) in patients with type 2 diabetes and to assess whether it is useful for detection of diabetic peripheral neuropathy (DPN).

Risk behavior score: a practical approach for assessing risk among men who have sex with men in Brazil

HIV/AIDS epidemic is not well controlled, and multiple sexual behavior factors help explain high rates of HIV infection among men who have sex with men (MSM). This article proposes to exam the use of a potential risk behavior score for HIV infection, based on the type and number of sexual partners, and condom use, and their associated factors in a sample of MSM in Brazil. A cross sectional RDS (Respondent Driven Sampling) study was performed among 3738 MSM aged 18+ years old from ten Brazilian cities. The risk behavior score was composed by the number of male partners and anal condom use in the last year with steady, casual, and commercial partners. Most participants were 25+ years old (58.1%), non-white (83.1%), and single (84.9%). Final weighted ordinal logistic model showed that age ≤ 25 years old (p = 0.037), homosexual or bisexual identity (p < 0.001), sexual initiation before 15-year-old (p < 0.001), having sex with men only in the last 12 months (p < 0.001), frequent alcohol and illicit drug use (p < 0.001), and use of local sites to meet sexual partners in the last month were independently associated with higher scores of risky behavior. Specific strategies should be developed aimed at the MSM population. Additionally, pre-exposed prophylaxis (Prep) should be considered for those at higher score as a strategy for reducing risk for HIV infection in this population.     

Predictors of mortality in multidrug-resistant tuberculosis patients from Brazilian reference centers, 2005 to 2012

Objectives

To determine the main predictors of death in multidrug-resistant (MDRTB) patients from Brazil.

Collection of WBC-reduced single-donor PLT concentrates with a new blood cell separator: results of a multicenter study

BACKGROUND: A new cell separator (COM.TEC, Fresenius) was recently developed aimed at efficient collection of WBC-reduced single-donor PLT concentrates (SDPs). STUDY DESIGN AND METHODS: Five German centers collected 554 WBC-reduced SDPs with help of the COM.TEC cell separator. Two multicenter cell counting studies were performed at the beginning and at the end of the study to document uniform counting results among the participating centers. RESULTS: A total of 441 (79.6%) PLT collections were included in the study according to the protocol. A total of 342 single-dose and 99 double-dose SDPs were collected. For single-dose SDPs, an average blood volume of 2826 +/- 409 mL was processed in a donation time of 55 +/- 11 minutes. Mean PLT yield of these products was 3.11 x 1011+/- 0.40 x 1011 and the WBC contamination was 0.11 x 106+/- 0.20 x 106. For double-dose SDPs (PLT count, 5.29 +/- 0.93 x 1011), 3943 +/- 639 mL was processed. The average difference between the target and the collected PLT concentration was -2.8 +/- 12.0 percent for single-dose SDPs and -1.8 +/- 9.5 for double-dose SDPs, respectively. The collection efficiency was 53.7 +/- 5.8 percent for single-dose SDPs and 58.2 +/- 6.2 percent for double-dose SDPs. If all results of each sample from the counting study were set to unity (to the mean over all centers), most PLT determinations were very similar to the mean, for example, near or 1 if set to unity. CONCLUSION: The COM.TEC machine makes it possible to obtain WBC-reduced SDPs that comply with current standards.