Absolute CD4 Counts Research Articles

Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia

There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib. We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL cells, T cells and monocytes. The immunophenotyping of CLL and immune cells in peripheral blood was performed on 16 high-risk CLL patients treated with ibrutinib. After early ibrutinib administration, the HLA-DR expression on CLL cells reduced (P = 0.032), accompanied by an increase in CLL cell counts in peripheral blood (P = 0.001). In vitro culturing of CLL cells with ibrutinib also revealed the reduction in the HLA-DR expression at protein and mRNA levels (P < 0.01). The decrease in HLA-DR on CLL cells after the first month was followed by the gradual increase of its expression by the 12th month (P = 0.001). A one-month follow-up resulted in elevated absolute counts of CD4+ (P = 0.002) and CD8+ (P < 0.001) T cells as well as CD4+ and CD8+ cells bearing HLA-DR (P < 0.01). The long-term administration of ibrutinib was associated with the increased numbers of CD4+ bearing HLA-DR (P = 0.006) and elevation of HLA-DR expression on all monocyte subsets (P ≤ 0.004). Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells and monocytes. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P24. Matched-pair cohort study of spinal surgery in HIV-infected patients: minimum one-year follow-up

BACKGROUND CONTEXT With the overall advancement in management of patients with human immunodeficiency virus (HIV) infection/AIDS, especially antiretroviral therapy regimens, HIV infection is now considered as a chronic disease and the longevity of these patients has significantly improved for the last two decades. As such, an increasing number of patients with HIV-infection are now potential candidates for elective surgical procedures such as spine surgery. In 2015, an estimated 1.1million adults and adolescents were living with HIV and 39,782 patients were newly diagnosed with HIV infection annually in 2016 (CDC data). Despite this increasing prevalence and incidence of the disease, the literature regarding clinical outcomes of spine surgery in patients with HIV is surprisingly scarce. As is the same as patients with other concurrent immunocompromising co-morbidities such as steroid use, diabetes mellitus, organ recipients, and/or chemo or radiation therapy, postoperative infection is one of the most concerning complications. Furthermore, bone mineral densities of HIV-infected patients are reported to be lower than noninfected controls, which could have some potential indications for worse long-term outcomes such as pseudoarthrosis. Thus, we aimed to characterize clinical outcomes of spine surgery in patients with HIV infection in order to facilitate judicious patient selection and comprehensive informed consent, which are of paramount importance in surgical decision-making processes for this high-risk cohort. PURPOSE Summarize clinical outcomes of spine surgery in patients with HIV, such as readmission rate, infectious complications, fusion rate, and mortality to address surgical indications for this specific cohort. STUDY DESIGN/SETTING Retrospective, single-center, propensity-matched cohort. PATIENT SAMPLE Patients who underwent spine surgery with HIV infection were included and compared with a matched-cohort without HIV infection OUTCOME MEASURES CD4 absolute count/uL, HIV-1 RNA copy numbers/mL, 30-day readmission rate, 90-day medical complication rate, one-year surgical site infectious complication rate, one-year fusion rate, and one-year mortality METHODS Single-center, retrospective data review from 2010 to 2016 yielded a total of 4,968 patients of spine surgery. Amongst those, 45 patients had HIV infection. Patients from the database were propensity-matched for age, sex, diagnoses, procedures, co-morbidities other than HIV at a 1:2 ratio, which yielded 90 matched-patients. Clinical outcomes of (A) 45 patients with HIV infection and (B) 90 matched-patients were compared and statistically analyzed. Intergroup comparison of binary variables was performed via Fisher's exact test. Intergroup comparison of continuous variables was achieved using unpaired t-tests. All reported p values are 2-sided and p values RESULTS No statistically significant differences were noted for baseline characteristics including age, sex, diagnoses, procedures, and co-morbidities. There were no statistically significant intergroup differences in operative data such as operative time and operated levels. the HIV-infected patient group had higher rates of 30-day readmission (11.1% vs. 2.2%, P=.04), one-year surgical site infectious complication (13.3% vs. 3.3%, P=.06), and one-year pseudoarthrosis (17.8% vs. 4.4%, P=.02) as well as longer hospital stay (6.8days vs. 4.6days, p CONCLUSIONS Spinal surgery in HIV-infected patients was associated with worse short- and long-term clinical outcomes, including higher rates of 30-day readmission, one-year infectious complication rate, and one-year pseudoarthrosis rate. Furthermore, CD4 absolute count may have some role in preoperative risk stratification. These results warrant further investigation of this cohort on multicenter, prospective basis, which should facilitate better patient selection for spine surgery and detailed informed consent, thereby potentially benefitting patients with HIV infection in the future.

Effect of Antihuman T Lymphocyte Globulin on Immune Recovery after Myeloablative Allogeneic Stem Cell Transplantation with Matched Unrelated Donors: Analysis of Immune Reconstitution in a Double-Blind Randomized Controlled Trial

We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) versus placebo. In a companion study we performed immunophenotypic analysis to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. The randomized study (n = 254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA-matched unrelated donors. Ninety-one patients consented for the companion IR study (ATLG = 44, placebo = 47). Blood samples were collected on days 30, 100, 180, and 360 after hematopoietic cell transplantation (HCT), and multiparameter flow cytometry was performed in a blinded fashion. Reconstitution of CD3+ and CD4+ T cells was delayed up to 6 months post-HCT in the ATLG arm, whereas absolute regulatory T cell (Treg) (CD4+25+127-) numbers were lower only in the first 100 days. Analysis of the CD4+ Treg and conventional T cells (Tconv) (CD4+25–127+) compartments showed a profound absence of naive Tregs and Tconv in the first 100 days post-HCT, with very slow recovery for 1 year. B cell and natural killer cell recovery were similar in each arm. Higher absolute counts of CD3+, CD4+, CD8+ T, Tregs, and Tconv were associated with improved overall survival, progression-free survival, and nonrelapse mortality but not moderate/severe cGVHD. Although ATLG delays CD3+ and CD4+ T cell recovery post-transplant, it has a relative Treg sparing effect after the early post-HCT period, with possible implications for protection from cGVHD. ATLG severely compromises the generation of naive CD4+ cells (Treg and Tconv), potentially affecting the diversity of the TCR repertoire and T cell responses against malignancy and infection.

Deviations in Peripheral Blood Cell Populations are Associated with the Stage of Primary Biliary Cholangitis and Presence of Itching

To evaluate the role of Th17, Treg cells, activated T CD3+ and B CD19+ lymphocytes in primary biliary cholangitis (PBC) patients. 40 female patients with PBC and 20 healthy donors were enrolled in this study. The percentages and absolute counts of Th17, Treg, activated T CD3+, B CD19+, NK, NKT-like lymphocytes were measured by flow cytometry. Our research revealed significantly lower frequencies and absolute counts of CD4+CD25+FOXP3+ Treg cells (p < 0.0001), higher percentages and absolute counts of Th17 cells (IL-17A+CD3+CD4+; p < 0.0001 and p = 0.009, respectively), CD3−/CD16+CD56+ NK cells (p < 0.0001 and p = 0.039, respectively), CD3+/CD16+CD56+ NKT-like cells (p < 0.0001 and p = 0.048, respectively). There were also higher percentages and numbers of B CD19+ lymphocytes (p = 0.002 and p = 0.001, respectively) and higher percentages and absolute counts of activated B CD19+CD25+ cells (p = 0.007 and p = 0.002, respectively). Moreover, we observed a statistically significant correlation between the presence of itching and particular peripheral blood subpopulations in PBC patients. Absolute counts of both CD4+CD3+ cells (p = 0.0119) and CD3+CD25+ cells (p = 0.0329) were lower in patients with pruritus. A similar dependency was noted in reference to percentages of NKT-like cells (CD3+/CD16+CD56+; p = 0.0359) and (CD3+) T lymphocytes (p = 0.0302). Th17 and Treg cells are involved in the course of PBC. There is also the association between the pruritus and peripheral blood subpopulations.

Differences of serum interleukin-6 levels in normotensive and preeclampsia women

Red cell distribution width (RDW) has been shown higher with the increase of inflammatory activity. As CD4 count is not available in all cities in Indonesia, RDW was hoped to be the next promising marker to predict the progression of HIV infection. This study aims to find the association of RDW with aCD4 count in HIV-positive reproductive women in Indonesia. It was a prospective cross sectional study enrolled 37 consented outpatients HIV-positive reproductive women in Haji Adam Malik General Hospital, Medan, Indonesia. A 10 mL blood was taken, separated into two tubes for complete blood count and CD4 count. Data were collected and analyzed with SPSS 19.Mean CD4 absolute was lowest in >14.5% RDW group but without statistical significance. By classify CD4 absolute count, CD4 absolute ≤350/mm3 showed significantly higher RDW than CD4 absolute >350/mm3 (13.98±2.10% vs 12.79±0.88%; p=0.02). No correlation was between RDW and CD4 absolute, as well as, with CD4%.In conclusion, high RDW can be a promising marker to predict the low CD4 count in HIV-positive reproductive women within antiretroviral therapy.

Phase 2 Trials with Mgta-456, Single Cord Blood Units (CBU) Expanded with an Aryl Hydrocarbon Receptor (AHR) Antagonist, Demonstrate Uniform Engraftment and Rapid Hematopoietic Recovery in Patients Following Myeloablative or Non-Myeloablative Conditioning

Background. The use of umbilical cord blood (UCB) in transplant has been limited by the low number of CD34+ cells, resulting in prolonged periods of cytopenia for patients and high risk of graft failure, thereby restricting its widespread application. MGTA-456 is the hematopoietic cell product after cord blood CD34+ cells are placed in expansion culture for 15 days with an aryl hydrocarbon receptor (AHR) antagonist in the presence of SCF, Flt-3L, IL-6 and TPO. In a prior Phase 1/2 safety study, 18 patients received MGTA-456, its accompanying CD34negfraction and a larger, unexpanded UCB unit. All patients engrafted at a median of 14.5 days (range, 7-23), significantly faster than similarly treated historical controls (p<0.01). Based on these results, two Phase 2 studies were initiated to evaluate the effectiveness of MGTA-456 as a stand-alone graft after myeloablative conditioning (MAC) or non-myeloablative conditioning (NMAC).Patients and Methods : Twenty patients with high-risk hematologic malignancy and a partially HLA-matched CBU were enrolled; 10 were treated with cyclophosphamide (CY) 120 mg/kg, fludarabine (FLU) 75 mg/m2 and total body irradiation (TBI) 1320 cGy (MAC) and 10 with CY 50 mg/kg, FLU 200 mg/m2 and TBI 200 cGy (NMAC). All patients received cyclosporine and mycophenolate mofetil post-transplant immunoprophylaxis. Expansion was low in 2 UCB units, therefore 18 patients received MGTA-456 and its CD34neg fraction.Results : Expansion culture yielded a median of 1,227 x 106 CD34+ cells (range, 201-8969) as compared to the input number of 4.2 x 106 (range, 1.4-16.3) after CD34 selection - a 324-fold (range, 42-1643) expansion of CD34+ cells. As transplant results vary by intensity of the conditioning, patient outcomes were compared to similarly treated historical cohorts between 2006 and 2015 (n=151 MAC; n=132 NMAC). For both groups, demographics were similar except for more recent year of transplant for recipients of MGTA-456. For recipients of MAC, MGTA-456 engrafted in all patients at a median of 14 days (range, 7-32) as compared to 89% engraftment at a median of 23 days (range, 19-31) in the control population (p<0.01, see Figure 1). Complete chimerism was rapid for both myeloid and T cells with no late graft failures; the longest follow-up was 5.6 years in recipients of MGTA-456. For recipients of NMAC, MGTA-456 also engrafted in all patients at a median of 7 days (range, 6-14) as compared to 94% engraftment at a median of 15 days (range, 7-22). In contrast to complete chimerism seen after MAC, chimerism is often mixed for the first month in both myeloid and T cells after NMAC. Compared to the historical cohort, recipients of MGTA-456 had more rapid chimerism after NMAC. CD34 cell dose correlates with speed of recovery but only in recipients with MAC; in recipients of NMAC, recovery is uniformly rapid regardless of CD34 cell dose. Additionally, immune recovery as measured by an absolute CD4 count >200/uL was achieved at day 60 (median) in recipients of MGTA-456 regardless of conditioning regimen. Results were also encouraging for other transplant outcomes. For recipients of MGTA-456 compared to the historical cohort after MAC, incidence of acute GVHD (aGVHD) grade 3-4 was 22% vs 24%; chronic GVHD (cGVHD), 11% vs 21%; transplant-related mortality (TRM), 11% vs 34%; and overall survival (OS), 67% vs 55%. After NMAC, results were similar between cohorts except for a higher risk of aGVHD in recipients of MGTA-456 (aGVHD 3-4, 43% vs 15%; cGVHD, 0% vs 19%; TRM, 22% vs 20%; and OS, 44% vs 49%). The increased rate of aGVHD in the NMAC cohort likely reflects non-compliance with prescribed GVHD immunoprophylaxis in 2 of 9 recipients.Conclusion : In these studies, MGTA-456 significantly accelerated hematopoietic recovery and abrogated the engraftment barrier typically associated with UCB transplantation. The marked expansion of CD34+ cells in MGTA-456 suggests that a significant number of patients will have an adequate single CBU and better HLA matched graft since a greater proportion of the cord blood inventory will be available irrespective of weight. Given these promising results, additional studies are being planned. [Display omitted] DisclosuresWagner:Novartis: Research Funding; Magenta Therapeutics: Research Funding. Brunstein:Novartis: Research Funding; Magenta Therapeutics: Research Funding. Boitano:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties; Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. McKenna:Magenta Therapeutics: Research Funding; Novartis: Research Funding. Sanna:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Bleul:Hoffmann-La Roche AG: Employment. Cooke:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties.

Helios\u2009+\u2009Regulatory T cell frequencies are correlated with control of viral replication and recovery of absolute CD4 T cells counts in early HIV-1 infection

BackgroundThe acute phase of HIV infection is characterized by massive depletion of CD4 T cells, high viral plasma levels and pronounced systemic immune activation. Regulatory T cells (Tregs) have the potential to control systemic immune activation but also to suppress antigen specific T and B cell response. The co-expression of FoxP3 and Helios transcription factors, has been described for identification of highly suppressive Tregs. The aim of this study was to characterize the phenotype of classic Tregs during early HIV infection, and to assess the correlations between the frequencies and phenotype of Tregs with the plasma viral load, CD4 counts, immune activation and the frequency of antibodies reactive to HIV-1 proteins, measured by an immunochromatographic test.ResultsThe relative frequency of classic Tregs cells in peripheral blood correlated positively with HIV viral load and immune activation of CD8 T cells, and inversely with absolute CD4 counts and development of anti-HIV antibodies in subjects with early HIV infection. However, the expression of Helios in classic Tregs was inversely correlated with viral replication and immune activation, and positively with recovery of CD4 T cell counts and appearance of antibodies reactive to HIV-1 proteins.ConclusionThese results raise the hypothesis that classic Tregs are inefficient at controlling systemic immune activation in subjects with early HIV infection and may be associated with delayed production of antibodies against HIV proteins, delaying the control of viral replication. Conversely, Helios expressing Tregs might contribute to control of viral replication by mechanisms involving the limitation of systemic immune activation.

Alveolar T-helper 17 responses to streptococcus pneumoniae are preserved in ART-untreated and treated HIV-infected Malawian adults

We explored if HIV infection is associated with impaired T-Helper 17 responses against Streptococcus pneumoniae in the lung. We recruited 30 HIV-uninfected healthy controls, 23 asymptomatic HIV-infected adults not on ART, and 40 asymptomatic HIV-infected adults on ART (Median time 3.5yrs), in whom we collected bronchoalveolar lavage fluid. We measured alveolar CD4+ T cell immune responses following stimulation with pneumococcal cell culture supernatant using flow cytometry-based intracellular cytokine staining. We found that the proportion of alveolar CD4+ T cells producing IL-17A following stimulation with pneumococcal cell culture supernatant (CCS) was similar between HIV-uninfected controls and ART-naïve HIV-infected adults (0.10% vs. 0.14%; p=0.9273). In contrast, the proportion and relative absolute counts of CD4+ T cells producing IL-17A in response to pneumococcal CCS were higher in ART-treated HIV-infected adults compared HIV-uninfected controls (0.22% vs. 0.10%, p=0.0166; 5420 vs. 1902 cells/100ml BAL fluid; p=0.0519). The increase in relative absolute numbers of IL-17A-producing alveolar CD4+ T cells in ART-treated individuals was not correlated with the peripheral blood CD4+ T cell count (r=-0.1876, p=0.1785). Alveolar Th17 responses against S. pneumoniae are preserved in HIV-infected adults. This suggests that there are other alternative mechanisms that are altered in HIV-infected individuals that render them more susceptible to pneumococcal pneumonia.

Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health?

Antiretroviral treatment (ART) has transformed human immunodeficiency virus (HIV) from a deadly disease to a chronic illness that potentially has little effect on life expectancy. Modern ART can eliminate viremia and lower the risk of transmission. National data from the United States demonstrate that 81% of infected individuals receiving ART are virally suppressed [1]. With treatment available, HIV morbidity and mortality are not determined by opportunistic infections or AIDS-defining illnesses but rather by non-AIDS–defining conditions, including cardiovascular disease, liver disease, kidney disease, malignancies, neurocognitive disorders, and even autoimmune diseases [2]. To some, autoimmunity coexisting with HIV may be surprising; however, its presence illustrates how HIV’s immunopathology is more consistent with immune dysfunction than immune suppression alone. HIV viral load and the resulting decrease in absolute CD4 T cells have historically served as biomarkers for HIV’s immune suppression and response to treatment. However, with successful modern ART and viral suppression, absolute CD4 count and HIV viral load may not accurately reflect the risks facing patients because immune dysfunction persists despite normalization of CD4 counts [3]. One explanation is that these markers fail to truly describe HIV’s overall immune dysfunction contributing to today’s morbidity and mortality. The CD4/CD8 ratio more accurately describes this overall immune dysfunction and may be a better biomarker for disease progression, response to treatment, morbidity, and mortality for the virally suppressed. A greater understanding of the CD4/CD8 ratio and the impact of its manipulation should be a target for future HIV research.

CD4 Lymphocyte Enumeration and Hemoglobin Assessment Aid for Priority Decisions: A Multisite Evaluation of the BD FACSPresto™ System.

Background:The BD FACSPresto™ system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites.Methods:Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur™ system, and for Hb, using the Sysmex® KX-21N™ analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs.Results:For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96–1.05 and R2 ≥0.96; Hb slopes were ≥1.00 and R2 ≥0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot.Conclusion:The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems.

Acute glutamine ingestion modulates lymphocytic responses to exhaustive exercise in the heat.

The purpose of this study was to determine if acute intake of glutamine modulates homeostatic, hematologic, immune, and inflammatory responses to exhaustive exercise in the heat. Thirteen healthy, untrained young men participated in this randomized, double-blind, placebo-controlled, crossover study. They served as their own control and completed 2 trials of treadmill exercise at 40% maximal oxygen uptake to exhaustion in a hot environment (temperature, 38.0 ± 1.0 °C; relative humidity, 60.0% ± 5.0%; oxygen, 20.8%) following placebo (PLA) and glutamine (GLN) consumption. Heart rate, gastrointestinal temperature, forehead temperature, the rating of perceived exertion, and body weight were measured. Blood samples were collected before and after exercise. After exhaustive exercise in the heat (PLA vs. GLN: 42.0 ± 9.5 vs. 39.6 ± 7.8 min, p > 0.05), significant changes in homeostatic, hematologic, and immune parameters (elevated natural killer (NK) cells and neutrophils, and reduced CD4+/CD8+ ratio and CD19+ lymphocytes) were found in the control group owing to the time effect (p < 0.05). Moreover, a condition × time interaction effect was observed for the absolute count of CD3+ (F = 4.26, p < 0.05) and CD3+CD8+ T lymphocytes (F = 4.27, p < 0.05), which were elevated following acute glutamine intervention. While a potential interaction effect was also observed for the absolute count of CD3+CD4+ T lymphocytes (F = 3.21, p = 0.08), no condition or interaction effects were found for any other outcome measures. The results of this study suggest that acute glutamine ingestion evokes CD3+ and CD3+CD8+ T lymphocytosis but does not modulate neutrophil and NK cell leukocytosis and immune disturbances after exhaustive exercise in the heat.

Hemoptysis in an AIDS Patient

SESSION TITLE: Lung Pathology 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Inflammatory myofibroblastic tumor (IMT) is a rare tumor predominantly found in children. IMTs can involve any organ but the lung is most frequently involved. Here, we report a case of IMT in an HIV-positive adult with hemoptysis CASE PRESENTATION: 46 year old black male with HIV was admitted with hemoptysis. He endorsed dyspnea and weight loss and was not adherent to HAART. Absolute CD4 count on admission was 15 cells/mm3 and interferon gamma release assay was negative. CXR showed a focal opacity in the right upper lobe (RUL) and CT scan demonstrated a wedge-shaped opacity in the RUL. Sputum was negative for acid-fast bacilli. Bronchoscopy demonstrated purulent secretions from the RUL and BAL yielded blood-tinged fluid with predominance of neutrophils and macrophages. Transbronchial biopsies (TBBx) demonstrated an inflammatory infiltrate of dendritic cells, multinucleated giant cells, plasma cells, and eosinophils in a background of bland spindle cells consistent with IMT. Immunohistochemical staining was positive for muscle-specific actin and negative for anaplastic lymphoma kinase (ALK-1). Acid fast staining was negative. There was focal positivity for Epstein-Barr virus (EBV) and Human Herpesvirus 8 (HHV-8). Biopsy and BAL cultures ultimately were positive for M. avium complex (MAC). He was a poor candidate for surgical resection and was discharged home on standard three-drug therapy for MAC and HAART. DISCUSSION: IMTs represent less than 1% of all lung tumors. Pathogenesis and neoplastic potential remains uncertain. Association with infections such as MAC, EBV, and HHV-8 has been reported. Complete resection is the treatment of choice for diagnostic and therapeutic purposes. Resolution has been reported with treatment of underlying infection in non-surgical candidates. Steroids and tyrosine kinase inhibition have also been used for ALK-1 positive tumors with some success. CONCLUSIONS: IMT is an uncommon clinical entity that may mimic conditions such as malignancy or an infectious processes. Here we have described a biopsy-proven IMT via TBBx in a patient with HIV and MAC infection. We identified only one other case in the literature of pulmonary IMT in an HIV-positive individual. Reference #1: S. Cambrea, G. Resul, M. Cambrea, F. Vasilescu, A. Benedetto. Pulmonary inflammatory myofibroblastic tumor in an AIDS patient. Rom J Morphol Embryol Rep, 55 (2) (2014), p 407-412. Reference #2: J. Yu, W. Li, D. Li, Z. Zhang, T. Yu. Pulmonary inflammatory myofibroblastic tumor mimics lung cancer. Thoracic Cancer, (5) (2014), p 271-274. DISCLOSURE: The following authors have nothing to disclose: Jeet Lund, Joe Pressler, Clifford Coile, Jose Lucar Lloveras, Shradha Ahuja No Product/Research Disclosure Information

The Effect of Ophthalmic Artery Chemosurgery on Immune Function in Retinoblastoma Patients: A Single Institution Retrospective Analysis.

Ophthalmic artery chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting Pneumocystis pneumonia prophylaxis. IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC. Twenty-three patients received ≥3 cycles of OAC and had immune function testing (absolute CD4 count) performed at a median of 34 days postcompletion of therapy (range, 15 to 63 d). Only 1 patient had a low absolute CD4 count of 189 cells/μL (normal, 359 to 1570 cells/μL) 2 and a half months after IV carboplatin and 28 days after their third dose of OAC. This patient was found to have coexisting hypogammaglobulinemia. Repeat immune function testing normalized through continued OAC treatment. Clinically significant immune suppression appears rare following OAC alone, but patients previously treated with IV chemotherapy may be immunosuppressed and may benefit from pneumocystis pneumonia prophylaxis until the CD4 count recovers.

Delayed lymphocyte re-population following discontinuation of dimethyl fumarate and after switching to other disease modifying drug therapies

BackgroundDimethyl fumarate (DMF) reduces absolute lymphocyte counts, CD4, and CD8 counts, without significantly affecting total white blood cell counts. However, the recovery rate of these cells after discontinuation of DMF is unknown. The effect of subsequent disease modifying therapies (DMTs) on re-population rate is also unknown. Objectives1. To study the re-population rate of absolute lymphocytes, CD4, and CD8 counts back to baseline after discontinuation of DMF. 2. To measure the effect of subsequent DMTs on the re-population rate of these cells after DMF therapy. 3. To study the effect of the duration of exposure to DMF on repopulation of these cells. MethodsA retrospective chart review of subjects who had discontinued DMF and in whom, CBC with differential, CD4 and CD8 counts were available at baseline, discontinuation and at follow-up (n = 113). Linear mixed models were used to analyze and assess linear trends in lymphocyte counts after DMF had been discontinued. ResultsDMF causes a significant drop in absolute lymphocyte, CD4, and CD8 counts. Re-population of these cells after discontinuation of DMF is significantly delayed, irrespective of whether or not a subsequent DMT is used, although there is a difference in re-population rate among DMTs. The re-population rate is also dependent on the duration of time patients have been exposed to DMF; longer exposure was associated with more delayed recovery. ConclusionDuring this 30 month study period, re-population rates were significantly delayed post-DMF, irrespective of what subsequent DMT the patients received. Furthermore, no recovery of lymphocyte counts occurred in patients who were started on fingolimod or alemtuzumab after DMF was discontinued; in fact there was a continued decline in all of the cell populations studied.

Study on CD4+T lymphocytes of new Uygur HIV infectors in Urumqi area

Objective: To understand the immune status of new Uygur HIV infectors in Urumqi area by detecting and analyzing CD4+T lymphocytes. Methods: Flow cytometry was used to detect absolute counts of CD4+T lymphocytes in 92 whole blood samples and the Student’s t test was used for analysis. Results: The mean absolute counts of CD4+T lymphocytes of 92 new Uygur HIV infectors was (305.9 ± 168.3) cells/μL. No statistical significances were found in different genders and different transmission routes (P > 0.05). A negative correlation was showed between absolute counts of CD4+T lymphocytes and HIV viral load. Conclusions: Two third of the new Uygur HIV infectors in Urumqi area have entered the AIDS phase, so monitoring and antiviral therapy were needed timely. Local government must strengthen publicity and enlarge the monitoring range of CD4+T lymphocytes. Early diagnosis and intervention could improve the survival quality of HIV infectors.

Low utility of serum 25–hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 in predicting peripheral Treg and Th17 cell counts in ESRD and renal transplant patients

BackgroundVitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. MethodsEighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study. The absolute counts of CD4+ and CD8+ T, CD16+ CD56+ NK, CD19+ B, CD4+ CD25+ CD127- Foxp3+ (Tregs), Helios+ Tregs, CD38+ Tregs, and CD4+ CD17+ (Th17) cells were analyzed in peripheral blood in both patient groups. In addition, serum 25 (OH) D3, 1, 25 (OH)2 D3, IL-6, IL-17, IL-23, and TGF-β1 were measured. The association between lymphocyte subset counts and 1, 25 (OH)2 D3 or 25 (OH) D3 was studied, as was the association between serum IL-6, IL-17, IL-23, or TGF-β1 and 1,25 (OH)2 D3 or 25 (OH) D3. ResultsSerum 25 (OH) D3 and 1,25 (OH)2 D3 levels were not independently associated with peripheral CD4+ T, CD19+ B, CD16+ CD56+ NK, Treg, or Th17 cell counts. In contrast to serum 25 (OH) D3, serum1, 25 (OH)2 D3 was positively associated with CD8+ T cells counts in renal transplant recipients. ConclusionOur findings indicate low utility of serum 25 (OH) D3 and 1, 25 (OH)2 D3 levels in predicting a change in lymphocyte subset counts in ESRD and renal transplant patients.

Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. We performed a retrospective review of clinical and laboratory studies for 26 infants collected from 7 New York State referral centers from 2010 to 2016 with low TRECs (mean, 70copies/μl) and subnormal CD3 counts (mean, 1150/cubicmm). Over time absolute CD3 counts increased in 17 and decreased in 9; 22 (85%) have done well clinically regardless of absolute T cell values. Additional infants with TCL will continue to be identified in newborn screening panels. While most patients seem to do well clinically, parameters for diagnosis and monitoring have yet to be formalized, and additional information needs to be collected, causes and outcomes reported.

CD4+ T-cell, CD8+ T-cell, CD4+ /CD8+ ratio, and apoptosis as a response to induction phase chemotherapy in pediatric acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is a neoplastic disease resulting from somatic mutation in the lymphoid progenitor cells, often occuring in children aged 2-5 years, predominantly in males. Results from the induction phase of chemtherapy are used to measure success, but the failure remission rate is still high. Increased apoptosis of cancer cells, as induced by CD4+ and CD8+T-cells, is an indicator of prognosis and response to chemotherapy.Objective To assess for correlations between CD4+, CD8+, or CD4+/CD8+ ratio to the chemotherapy induction phase response (i.e., apoptosis) in pediatric ALL patients.Methods This observational analytical cohort study was done in 25 pediatric ALL patients. Whole blood (3 mL) with EDTA anticoagulant were used to measure absolute counts of CD4+, CD8+, and CD4+/CD8+ ratio. Peripheral blood mononuclear cells (PBMC) were examined for apoptosis. The principle of CD4+, CD8+ examination was bond between antigens on the surface of the leukocyte in the blood with fluorochrome labeled antibodies in the reagents, while the principle of apoptosis examination was FITC Annexin V will bonds with phosphatidylserine that moves out of the cell when the cell undergoes apoptosis, then intercalation with propidium iodide (PI). All examination were detected by flow cytometry BD FACSCalibur.Results Subjects were 25 newly-diagnosed, pediatric ALL patients (64% males and 36% females). Most subjects were 3 years of age (20%). Numbers of CD4+ and CD8+ cells, as well as CD4+/CD8+ were significantly decreased after chemotherapy. However, apoptosis was not significantly different before and after chemotherapy (P=0.689), There were significant negative correlations between apoptosis and CD4+ (P=0.002; rs=-0.584), and CD8+ (rs=-0.556; P=0.004), before chemotherapy. In addition, CD4+-delta and apoptosis-delta also had a significant positive correlation (rs=0.478; P=0.016). However, no correlation was found between the CD4+/CD8+ ratio and apoptosis, before or after chemotherapy.Conclusion There are significantly lower mean CD4+, CD8+, and CD4+/CD8+ ratio after chemotherapy than before. Also, there are significant correlations between CD4+-delta and apoptosis-delta, as well as between apoptosis and CD4+, CD8+, and CD4+/CD8+, before chemotherapy. CD4+, CD8+, and CD4+/CD8+ can be used to predict apoptosis before chemotherapy. In addition, CD4+-delta can be used to predict apoptosis-delta as a response to induction phase chemotherapy in pediatric ALL.

English

Antiretroviral (ART) regimen switch is a common occurrence in resource-limited settings where patients present late for care or with an AIDS-defining event. ART regimen switch can be attributed to several factors emanating from either the individual, program or facility level. This retrospective study was carried out in a resource-limited comprehensive facility in North-central Nigeria. Treatment records of 4,206 Adult HIV/AIDS patients initiated on first line ART regimen from 2006 to 2013 were extracted and examined for switch to second line ART regimen for the purpose of this study after ethical clearance had been sought. Absolute CD4 count, World Health Organisation (WHO) clinical stage and viral load results at treatment initiation, point of switch to second line and at the end of 2014 (end-point for the study) were obtained. About 75% of the 4,206 patients initiated on first line highly active antiretroviral therapy (HAART) were retained in care and were still on first line HAART at the end of 2014 with a significant difference in median CD4 count, BMI, WHO clinical staging and viral load at baseline compared to the end of the study period. Out of the 4,206 adults patients initiated on first line HAART, 71 were later switched to second line regimen due to either first-line immunological or virological failures although only 57 patients without traces of co-infection were included in this study. At end-point, a very high (87.7%) WHO defined immunological response was achieved. The study revealed that although immunologic and virologic response in patients before ART regimen switch was low, it improved tremendously after switch to second line regimen in all patients including those with available viral load results. The study results showed a 96.5% retention rate of patients switched to second line HAART and a correlation between virological suppression and immunological response. Key words: Immunological assessment, virologic response, HIV diagnosis, first line regimen, second line regimen.

Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis.

We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.