Telomerase Activity Increased and Telomere Length Shortened in Peripheral Blood Cells from Patients with Immune Thrombocytopenia

Objectives

To evaluate the telomere/telomerase system and its clinical significance in immune thrombocytopenia (ITP) patients.

Methods

A total of 237 ITP patients, 20 SLE patients and 200 age-and sex-matched healthy controls were included in this study. CD4⁺, CD8⁺ and CD19⁺ lymphocytes were purified by magnetic beads sorting from peripheral blood of 37 active chronic ITP patients and 22 age-and sex-matched healthy controls. Telomerase activity was assayed by Telo TTAGGG Telomerase PCR ELISA KIT. The relative telomere length of peripheral blood mononuclear cell (PBMC) was measured by a quantitative polymerase chain reaction-based method (Q-PCR) from 200 ITP patients and 178 age-and sex-matched healthy controls.

Results

Telomerase activity was increased in CD4⁺, CD8⁺ and CD19⁺ lymphocytes from ITP patients compared to those from healthy controls (p?=?0.000). The level of telomerase activity in CD19⁺ lymphocyte was higher than those in CD4⁺ and CD8⁺ lymphocytes. Telomerase activity of CD19+ lymphocytes had a modest negative correlation with platelet count in ITP patients (p?=?0.042). The relative telomere length of PBMC in ITP patients was significantly shorter than that in the healthy controls (p?=?0.002). Telomere length of PBMC in active ITP patients was significantly shorter than that in the controls (p?=?0.000) and a tendency to be shorter even in inactive ITP patients (p?=?0.065). Moreover, the telomere length in refractory and non-refractory ITP patients were both significantly shorter than that in the controls (p?=?0.025; p?=?0.000). However no significant difference in telomere length of PBMC was found between refractory ITP patients and non-refractory ITP patients (p?=?0.234).

Conclusion

An abnormal regulating telomere/telomerase system might be involved in the pathogenesis of ITP. Further studies may elucidate whether the telomere length could be considered as a predictive biomarker for the prognosis of ITP.     

Serum Adenosine Deaminase and Total Immunoglobulin G Correlate with Markers of Immune Activation and Inversely with CD4 Counts in Asymptomatic, Treatment-Naive HIV Infection

Purpose

HIV-infection is characterized by aberrant immune activation and ongoing inflammation. Markers of inflammation are now recognized to have prognostic value for adverse events, independent of viral loads and CD4 counts. This study aimed to delineate a panel of affordable markers of immune activation in untreated HIV-infection that may have an impact on the management of HIV in resource-limited settings.

Methods

This was a cross-sectional study of 86 untreated newly diagnosed HIV-infected patients and 54 matched controls attending a voluntary testing clinic in Cape Town, South Africa. Serum levels of adenosine deaminase (ADA), total immunoglobulin G (IgG), soluble CD14 and lipopolysaccharide-binding protein (LBP) were measured and correlated with CD4 counts, viral loads and expression of CD38 on CD8+ T cells.

Results

ADA, IgG and LBP were all significantly increased in the HIV infected group (p?<?0.0001) compared with uninfected controls. Soluble CD14 was also significantly increased (p?=?0.0187). Furthermore, all these parameters correlated inversely with CD4 counts (r?=??0.481 p?<?0.0001; r?=??0.561; p?<?0.0001; r?=??0.387 p?=?0.0007 and r?=??0.254 p?=?0.0240, respectively). Only ADA correlated with viral load (r?=?0.260 p?=?0.0172). Importantly, ADA, IgG and LBP correlated directly with %CD38 on CD8+ T cells (r?=?0.369 p?<?0.0001; r?=?0.284 p?=?0.001; r?=?0.408 p?=?0.0006, respectively).

Conclusion

Affordable parameters such as serum ADA and IgG correlated significantly with immune activation levels and markers of disease progression in untreated HIV-infection and therefore may add value to the management of these patients in resource-limited settings.     

Virological effectiveness and CD4+ T-cell increase over early and late courses in HIV infected patients on antiretroviral therapy: focus on HCV and anchor class received

Background

The aim of this study was to explore the effects of HCV co-infection on virological effectiveness and on CD4+ T-cell recovery in patients with an early and sustained virological response after HAART.

Methods

We performed a longitudinal analysis of 3,262 patients from the MASTER cohort, who started HAART from 2000 to 2008. Patients were stratified into 6 groups by HCV status and type of anchor class. The early virological outcome was the achievement of HIV RNA <500 copies/ml 4?C8?months after HAART initiation. Time to virological response was also evaluated by Kaplan-Meier analysis. The main outcome measure of early immunological response was the achievement of CD4+ T-cell increase by ??100/mm³ from baseline to month 4?C8 in virological responder patients. Late immunological outcome was absolute variation of CD4+ T-cell count with respect to baseline up to month 24. Multivariable analysis (ANCOVA) investigated predictors for this outcome.

Results

The early virological response was higher in HCV Ab-negative than HCV Ab-positive patients prescribed PI/r (92.2% versus 88%; p?=?0.01) or NNRTI (88.5% versus 84.7%; p?=?0.06). HCV Ab-positive serostatus was a significant predictor of a delayed virological suppression independently from other variables, including types of anchor class. Reactivity for HCV antibodies was associated with a lower probability of obtaining ??100/mm³ CD4+ increase within 8?months from HAART initiation in patients treated with PI/r (62.2% among HCV Ab-positive patients versus 70.9% among HCV Ab-negative patients; p?=?0.003) and NNRTI (63.7% versus 74.7%; p?p?=?0.013) and in those treated with NNRTI (p?=?0.002). This was confirmed at a multivariable analysis up to 12?months of follow-up.

Conclusions

In this large cohort, HCV Ab reactivity was associated with an inferior virological outcome and an independent association between HCV Ab-positivity and smaller CD4+ increase was evident up to 12?months of follow-up. Although the difference in CD4+ T-cell count was modest, a stricter follow-up and optimization of HAART strategy appear to be important in HIV patients co-infected by HCV. Moreover, our data support anti-HCV treatment leading to HCV eradication as a means to facilitate the achievement of the viro-immunological goals of HAART.     

Expansion of CD11b<Superscript>+</Superscript>Ly6G<Superscript>high</Superscript> and CD11b<Superscript>+</Superscript>CD49d<Superscript>+</Superscript> myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption

Objective

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.

Subjects

67 CD-1 mice and in vitro MDSC cultures.

Treatment

Adjuvant arthritis was induced by a subdermal injection of complete Freund’s adjuvant. LN was induced by illumination of 750 lx at night.

Methods

Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used.

Results

Increased levels of splenic CD11b⁺Ly6G^high and CD11b⁺CD49d⁺ myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b⁺Ly6G^high expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN.

Conclusions

Our study raises the possibility that CD11b⁺Ly6G^high and CD11b⁺CD49d⁺ MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

     

HCV RNA viral load is independent from CD4 cell count and plasma HIV RNA viral load in immunocompetent HIV-HCV co-infected patients: a 3-years follow-up study

Background

HCV RNA viral load is an important predictor of sustained virological response and, recently, a significant correlation with liver fibrosis was described. We investigated on possible influence of clinical and viro-immunological variables on HCV viral load in HIV-HCV co-infected patients over a study time of three years (2009-2012).

Methods

We retrospectively enrolled 98 adult patients with a diagnosis of chronic HIV infection in 2009, a diagnosis of chronic HCV infection with a detectable plasma HCV RNA in 2009 and 2012, HCV therapy-naïve or with failed and stopped antiviral treatment before June 2008. The following variables were recorded: age, gender, HCV genotype, IL28B rs12979860 CC genotype, HCV treatment status, advanced liver fibrosis diagnosis, antiretroviral therapy, CD4+ cell count, HCV viral load, HIV RNA (plasma HIV-1 RNA levels were measured from blood samples every three months at least). The correlation was established using linear regression analysis, analysis of variance and Fisher’s exact test. Comparisons between groups were performed using Fisher’s exact test, the independent samples t-test and the t-test for paired data, as appropriate, for continuous variables. A mixed mode (ME) maximum likelihood linear regression model was constructed to evaluate the dependence of HCV viral load.

Results

HCV RNA levels did not change significantly from 2009 to 2012 (from 3924650?±?5320177 IU/ml to 3085128?±?3372347 IU/ml, p?=?0.13); the CD4+ count increased significantly (from a mean of 576 to a mean of 654, p?=?0.003). Using linear regression, a positive correlation was observed for HCV load and genotype 1 (p?=?0.002), nonresponder status (p?=?0.04) and with interleukin 28B CC allele (p?=?0.05). Other studied covariates failed to reach a significant correlation.

Conclusions

The HCV RNA load, a known pretreatment predictor of response to antiviral therapy, was independent of the two main parameters of HIV disease, plasma HIV RNA and CD4 cell count, over an observation time of 3 years in patients with recovered or spontaneously maintained immunocompetence.

     

Characterization of Interleukin-33 and Soluble ST2 in Serum and Their Association with Disease Severity in Patients with Chronic Kidney Disease

Introduction

This study aims to test the serum levels of interleukin-33 (IL-33) and soluble ST2 (sST2) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity.

Methods

Sixty-nine patients with CKD were enrolled, disease severity was assessed, and clinical data were collected. Twelve healthy volunteers served as healthy individuals. Serum IL-33 and sST2 were tested by enzyme-linked immunosorbent assay.

Results

The patients were classified into five categories based on their estimated glomerular filtration rate (eGFR). No difference was found as to the serum concentration of IL-33 between CKD patients and healthy individuals (p?=?0.656), while a higher serum level of sST2 was found in CKD patients (p?=?0.003). The correlation analysis revealed a significant correlation between the serum level of sST2 and disease severity (r?=?0.586; p?p?=?0.001). Serum sST2 correlated with parathyroid hormone (r?=?0.412; p?r?=?0.545; p?r?=??0.494; p?Conclusion An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.     

Immune-Mediated Diseases and Immunodeficiencies Associated with Thymic Epithelial Neoplasms

Introduction

This retrospective study aimed to characterize the clinical hematological and immunological features of patients with thymic epithelial neoplasms.

Methods

From a cohort of 512 patients with thymic epithelial neoplasms, 79 patients diagnosed with autoimmune/immunodeficiency conditions or signs and/or symptoms suggesting an autoimmune or immunodeficiency state were evaluated by standard immunological and hematological testing.

Results

Elevated percentages of CD2+, CD3+, and CD8+ lymphocytes were observed in 44 (57.1%), 33 (41.8%), and 32 (40.5%) patients. Low CD4+ and CD19+ percentages were observed in 25 (31.6%) and 36 (46.2%), respectively; CD4+:CD8+ ratios were inverted in 18 (22.8%). IgG, IgA, and IgM levels were low in 12 (15.8%), 9 (11.7%) and 15 (19.7%) patients, respectively. Patients with immunodeficiency condition(s) were more likely to have high CD8+ percentages (p?=?0.040), low CD19+ percentages (p?=?0.025), and/or inverted CD4+/CD8+ ratios (p?=?0.034). Patients with autoimmune condition(s) were more likely to have a high/normal CD4+ percentage (p?=?0.038). High CD2+ percentages were associated with lower mean IgG and IgA levels (p?=?0.030 and p?=?0.017, respectively). High CD3+ and CD8+ percentages were associated with lower mean IgA levels (p?=?0.046 and p?=?0.013, respectively). Low CD19+ percentages were associated with lower mean IgG and IgA levels (p?=?0.004 and p?Conclusion Signs/symptoms and history of autoimmune and immunodeficiency conditions among patients with thymic epithelial neoplasms are associated with high frequencies of abnormalities in immunoglobulin levels and lymphocyte immunophenotypes, suggesting a role for their assessment.     

Decreased Levels of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Patients with Primary Antiphospholipid Syndrome

Introduction

CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cell dysfunction has been documented in various autoimmune disorders, but not in antiphospholipid syndrome (APS) so far.

Methods

In this cross-sectional study, we aim to investigate CD4⁺CD25⁺Foxp3⁺ Treg cells, CD3⁺CD19^? T cells and CD3^?CD19⁺ B cells in patients with primary APS and healthy controls. Cell subtypes were immunophenotyped using specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti-Foxp3, anti-CD19 PE) and flow cytometry.

Results

Twenty patients with APS and 20 age- and sex-matched controls were studied. The percentage of total lymphocytes, activated Th cells (CD4+CD25+), Treg cells and CD3^?CD19⁺ B cells were found significantly lower in APS patients as compared to controls (all p?<?0.05).

Conclusion

A dysfunction in CD4⁺CD25⁺Foxp3⁺ Treg cells may represent one of the mechanisms leading to autoimmunity in APS patients. The decreased number of CD3^?CD19⁺ B cells of APS patients warrants further elucidation.     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Pre-Biopsy Psychological Factors Predict Patient Biopsy Experience

Background

Excisional/surgical breast biopsy has been related to anticipatory emotional distress, and anticipatory distress has been associated with worse biopsy-related outcomes (e.g., pain, physical discomfort).

Purpose

The present study was designed to investigate (a) whether anticipatory distress before an image-guided breast biopsy would correlate with biopsy-related outcomes (pain and physical discomfort during the biopsy) and (b) whether type of distress (i.e., general anxiety, worry about the procedure, worry about biopsy results) would differentially relate to biopsy-related outcomes.

Methods

Fifty image-guided breast biopsy patients (mean age = 44.4 years) were administered questionnaires pre- and post-biopsy. Pre-biopsy, patients completed the Profile of Mood States–tension/anxiety subscale and two visual analog scale items (worry about the biopsy procedure, worry about the biopsy results). Post-biopsy, patients completed two visual analog scale items (pain and physical discomfort at their worst during the procedure).

Results

The following results were gathered: (1) Pre-biopsy worry about the procedure was significantly related to both pain (r?=?0.38, p?=?0.006) and physical discomfort (r?=?0.31, p?=?0.026); (2) pre-biopsy general anxiety was significantly related to pain (r?=?0.36, p?=?0.009), but not to physical discomfort; and (3) Pre-biopsy worry about the biopsy results did not significantly relate to pain or physical discomfort.

Conclusions

Worry about the procedure was the only variable found to be significantly correlated with both biopsy-related outcomes (pain and physical discomfort). From a clinical perspective, this item could be used as a brief screening tool to identify patients who might be at risk for poorer biopsy experiences and who might benefit from brief interventions to reduce pre-biopsy worry.     

Influence of Maternal Hyperglycemia on IL-10 and TNF-α Production: The Relationship with Perinatal Outcomes

Aims

This study was conducted to evaluate maternal and placental concentrations of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in pregnant women with glycemic mean (GM) < or ≥100 mg/dL, as well as correlate IL-10 and TNF-α placental concentrations with perinatal outcomes.

Methods

One hundred eighty-six pregnant women were distributed in groups determined by a GM <100 mg/dL or a GM ≥100 mg/dL. The GM, HbA1c levels, maternal and placental concentrations of IL-10 and TNF-α, and the correlation of placental cytokines with perinatal outcomes were evaluated.

Results

In maternal blood, the lowest concentrations of IL-10 (p?=?0.0019) and TNF-α (p?=?0.0185) were observed in the GM ≥100-mg/dL group. The placentas from GM ≥100 mg/dL group exhibited higher TNF-α concentrations (p?=?0.0385). Placental IL-10 directly correlated with hemoglobin (r?=?0.63; p?=?0.02) and insulin (r?=?0.78; p?=?0.01) levels in the umbilical cord and with 1-min (r?=?0.53; p?=?0.0095) and 5-min (r?=?0.69; p?=?0.0003) Apgar scores. Placental TNF-α displayed a tendency to inversely correlate with fetal weight (r?=??0.41; p?=?0.05).

Conclusion

Compared to GM <100 mg/dL, GM ≥100 mg/dL was associated with a reduction in maternal IL-10 and TNF-α concentrations and increased placental TNF-α production. Placental IL-10 production was similar in both groups studied and directly correlated with hemoglobin and umbilical cord insulin levels, as well as with the 1- and 5-min Apgar scores.     

Immunotherapy with interferon-α-induced dendritic cells for chronic HCV infection (the results of pilot clinical trial)

The key role of T cells in hepatitis C virus (HCV) elimination and the ability of dendritic cells (DCs) to induce antiviral T cell responses suggest that DC vaccines could be a promising approach in the treatment of chronic HCV infection. The aim of our study was to evaluate, whether immunotherapy with DCs is safe and elicits anti-HCV T cell responses. Ten patients with HCV (genotype 1) were vaccinated with monocyte-derived DCs, generated in the presence of IFN-α (IFN-DCs) and pulsed with recombinant HCV Core and NS3 proteins. Treatment schedule included four subcutaneous vaccinations with 1?week interval and six vaccinations with month interval. No serious adverse events or an increase in hepatitis C biochemical activity were registered after vaccination. Using ex vivo assays for the detection of proliferative responses, IFN-γ production and CD8⁺ degranulation have shown that immunotherapy elicited antigen-specific responses in all patients although individual heterogeneity existed within their types, magnitude, and timing. Core/NS3-specific proliferative response and CD8⁺ T cell degranulation have already been registered after the first course of vaccination. Of note, Core-specific responses had higher magnitude. The appearance of antigen-specific IFN-γ responses was registered after the second vaccination course. Vaccination did not cause Th2 response and expansion of the CD4⁺CD25⁺CD127^? regulatory T cells. Generated immune responses failed to provide virus elimination. Nevertheless, there were inverse correlations between viral load and NS3-specific proliferation (R _S?=?0.62; p?=?0.05) and IFN-γ secretion (R _S?=???0.82; p?=?0.001) at 6-month post-treatment period. Immunotherapy with IFN-DCs was safe and elicited HCV-specific T cell responses which were insufficient to eliminate viruses but could be implicated in the restriction of viral replication.     

B-lymphocyte Subpopulations in Patients with Selective IgA Deficiency

Introduction

Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD.

Materials and Methods

Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: na?ve (CD27^-IgD⁺), marginal zone cells (CD27⁺IgD⁺), class-switched memory cells (CD27⁺IgD^-), ??double-negative?? B cells (CD27^-IgD^-), transitional cells (IgM⁺⁺CD38⁺⁺), plasmablasts (CD38⁺⁺⁺IgM⁺ or IgM^-), and CD21^lowCD38^low cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons.

Results

Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both?P?P?=?0.035) as well as plasmablasts (P?lowCD38^low subset (P?=?0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27⁺IgD^- (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients.

Conclusion

Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients.     

Effect of a Telephone-Delivered Coronary Heart Disease Secondary Prevention Program (ProActive Heart) on Quality of Life and Health Behaviours: Primary Outcomes of a Randomised Controlled Trial

Background

Participation in coronary heart disease secondary prevention programs is low. Innovative programs to meet this treatment gap are required.

Purpose

To aim of this study is to describe the effectiveness of a telephone-delivered secondary prevention program for myocardial infarction patients.

Methods

Four hundred and thirty adult myocardial infarction patients in Brisbane, Australia were randomised to a 6-month secondary prevention program or usual care. Primary outcomes were health-related quality of life (Short Form-36) and physical activity (Active Australia Survey).

Results

Significant intervention effects were observed for health-related quality of life on the mental component summary score (p?=?0.02), and the social functioning (p?=?0.04) and role-emotional (p?=?0.03) subscales, compared with usual care. Intervention participants were also more likely to meet recommended levels of physical activity (p?=?0.02), body mass index (p?=?0.05), vegetable intake (p?=?0.04) and alcohol consumption (p?=?0.05).

Conclusions

Telephone-delivered secondary prevention programs can significantly improve health outcomes and could meet the treatment gap for myocardial infarction patients.     

Non Invasive Assessment of Lung Disease in Ataxia Telangiectasia by High-Field Magnetic Resonance Imaging

Purpose

A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable. We designed a study to evaluate lung changes using magnetic resonance imaging (MRI), and to investigate the relationships among severity and extent of pulmonary abnormalities and clinical, microbiological and functional data in children and young adults with AT.

Methods

Fifteen AT patients (age, 11.3 years; range, 6–31) underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified Helbich score.

Results

Although only 8 patients (53 %) had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in all. Bronchiectasis, peribronchial thickening, mucous plugging, and collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases, respectively, with no difference between subjects with or without respiratory symptoms. No difference in changes of specific scores was found between the two groups, but the total MRI score was higher in patients with respiratory symptoms (6.5 versus 5, respectively; p?=?0.02). Total or specific MRI scores were not associated with patients’ age. Of all scores, only mucous plugging subscore appeared significantly related to FEV₁ (r?=?0.7, p?=?0.04) and FEF_25–75% (r?=?0.9, p?=?0.001). MRI scores from patients with positive (n?=?5) or negative (n?=?10) sputum culture were not significantly different.

Conclusions

MRI is valuable in the assessment of extent and severity of pulmonary changes in children and adults with AT. It represents an helpful tool for the longitudinal evaluation of patients and may be also used as an outcome surrogate to track the effects of medications.     

Increased Plasma Interleukin-32 Expression in Patients with Neuromyelitis Optica

Purpose

Neuromyelitis optica (NMO) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The pathogenesis of NMO remains unclear. IL-32 is emerging as a critical molecule in the pathophysiology of immune-mediated chronic inflammatory diseases. Whether IL-32 levels are elevated in NMO patients is unclear. We aimed to determine whether IL-32 levels are elevated in NMO patients and explore its relationship with IL-6, IL-17, and Expanded Disability Status Scale (EDSS) scores.

Methods

Plasma IL-32α, IL-6 and IL-17A were measured by enzyme-linked immunosorbent assay in NMO (n?=?26), MS (n?=?23) and 22 healthy controls.

Results

We found IL-32α levels were higher in NMO patients compared with MS (p?=?0.020) and healthy controls (p?=?0.00001). IL-32α levels were increased in MS patients compared with controls (p?=?0.009). IL-32α positively correlated with IL-6 and IL-17A levels and EDSS scores in NMO patients.

Conclusions

In summary, plasma IL-32α levels are associated with inflammatory responses in NMO patients.     

Use of Combination Chemotherapy for Treatment of Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) in Patients with Common Variable Immunodeficiency (CVID)

Purpose

A subset of patients with common variable immunodeficiency (CVID) develops granulomatous and lymphocytic interstitial lung disease (GLILD), a restrictive lung disease associated with early mortality. The optimal therapy for GLILD is unknown. This study was undertaken to see if rituximab and azathioprine (combination chemotherapy) would improve pulmonary function and/or radiographic abnormalities in patients with CVID and GLILD.

Methods

A retrospective chart review of patients with CVID and GLILD who were treated with combination chemotherapy was performed. Complete pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans of the chest were done prior to therapy and >6 months later. HRCT scans of the chest were blinded, randomized, and scored independently (in pairs) by two radiologists. The differences between pre- and post-treatment HRCT scores and PFT parameters were analyzed.

Results

Seven patients with CVID and GLILD met inclusion criteria. Post-treatment increases were noted in both FEV1 (p?=?0.034) and FVC (p?=?0.043). HRCT scans of the chest demonstrated improvement in total score (p?=?0.018), pulmonary consolidations (p?=?0.041), ground-glass opacities (p?=?0.020) nodular opacities (p?=?0.024), and both the presence and extent of bronchial wall thickening (p?=?0.014, 0.026 respectively). No significant chemotherapy-related complications occurred.

Conclusions

Combination chemotherapy improved pulmonary function and decreased radiographic abnormalities in patients with CVID and GLILD.     

Persistence of a Large Population of Exhausted Monoclonal B cells in Mixed Cryoglobuliemia After the Eradication of Hepatitis C Virus Infection

Purpose

Functionally exhausted and mostly autoreactive B-cells with a peculiar CD21^lowCD11c⁺ phenotype accumulate in several human immunological disorders including common variable immunodeficiency, HIV infection and rheumatoid arthritis. In HCV-associated mixed cryoglobulinemia (MC) there is accumulation of exhausted clonal B cells expressing a V_H1-69-encoded cross-reactive idiotype; these cells are phenotypically heterogeneous, displaying either a CD21^lowCD11c⁺ or a marginal zone (MZ)-like (IgM⁺CD27⁺CD21⁺CD11c^-) phenotype. Irrespective of their phenotype, V_H1-69⁺ B-cells are unresponsive to the stimulation of Toll-like receptor 9 (TLR9). We investigated the fate of these cells after the eradication of HCV.

Methods

Fourteen MC patients were studied before and after antiviral therapy. V_H1-69⁺ B-cells were identified using the G6 monoclonal antibody and their phenotype and responsiveness to the stimulation of TLR9 were investigated.

Results

In seven virological non-responders, cryoglobulin levels and the number and phenotype of V_H1-69⁺ B cells remained substantially unchanged. By contrast, in sustained viral responders cryoglobulinemia subsided and the number of V_H1-69⁺ B cells declined. However, high proportions of MZ-like V_H1-69⁺ B cells retaining unresponsiveness to TLR9 stimulation persisted for several months in these patients.

Conclusions

Clonal expansion of CD21^low V_H1-69⁺ B cells may depend on continual stimulation by HCV, whereas their MZ-like counterparts may persist for years after the eradication of infection. Prolonged survival of exhausted MZ-like B cells after withdrawal of the initial inciting stimulus may contribute to the accumulation of autoreactive B cells in immunological disorders.