Susan Langan
Johns Hopkins University
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Featured researches published by Susan Langan.
The Journal of Infectious Diseases | 2002
Deepa S. Patke; Susan Langan; Lucy M. Carruth; Sheila M. Keating; Beulah P. Sabundayo; Joseph B. Margolick; Thomas C. Quinn; Robert C. Bollinger
T lymphocyte responses to human immunodeficiency virus (HIV) type 1 Gag were measured in 9 patients by interferon-gamma enzyme-linked immunospot assay at 3 time points within 12 months of infection. Patients with early recognition of HIV-1 Gag had lower subsequent HIV-1 load set points, as measured during the first 2 years of infection, compared with those of patients with undetectable Gag-specific responses (median, 4.27 vs. 5.05 log(10) HIV-1 RNA copies/mL, respectively; P=.028). An inverse correlation existed between the magnitude of the Gag-specific responses and the HIV-1 load set point (r=-0.733; P=.025). Early sustained T lymphocyte responses to HIV-1 Gag may be important for the establishment of virus load set point.
Journal of Leukocyte Biology | 2008
Adriana A. Byrnes; David M. Harris; Sowsan F. Atabani; Beulah P. Sabundayo; Susan Langan; Joseph B. Margolick; Christopher L. Karp
Suppressed IL‐12 production and maladaptive immune activation, both of which are ameliorated by successful highly active antiretroviral therapy (HAART), are thought to play important roles in the immunopathogenesis of chronic HIV infection. Despite the important effects of the immunological and virological events of early HIV infection on subsequent disease progression, IL‐12 production and immune activation in early infection remain under‐defined. To quantify IL‐12 production and immune activation during acute/early HIV infection, in the presence and absence of HAART, we performed a prospective, longitudinal study of participants in the Baltimore site of the Acute Infection and Early Disease Research Program, with cross‐sectional comparison to healthy control subjects. PBMC cytokine productive capacity and plasma immune activation markers [soluble CD8 (sCD8), sCD4, granzyme B, neopterin, β2‐microglobulin, sIL‐2R, sTNFRI, sTNFRII, and IL‐12p70] were quantified by ELISA. Notably, PBMC from patients with acute/early HIV infection exhibited in vivo IL‐12p70 production along with increased, maximal in vitro IL‐12 production. Further, despite evidence from plasma markers of generalized immune activation, no elevation in plasma levels of sCD4 was observed, suggesting relative blunting of in vivo CD4+ T cell activation from the beginning of HIV infection. Finally, despite successful virological responses to HAART, heightened in vivo CD8+ T cell activation, IL‐12 production, and IFN activity were sustained for at least 6 months during primary HIV infection. These data underscore the need for comparative mechanistic analysis of the immunobiology of early and chronic HIV infection.
The Journal of Infectious Diseases | 2014
Huifen Li; Joseph B. Margolick; Jay H. Bream; Tricia L. Nilles; Susan Langan; Hanhvy T. Bui; Andrew W. Sylwester; Louis J. Picker; Sean X. Leng
Studies of T-cell immunity to human cytomegalovirus (CMV) primarily reflect anti-CMV pp65 or immediate early antigen 1 (IE-1) activity. We assessed responses of T cells from human immunodeficiency virus (HIV)-negative and HIV-infected men to peptide pools spanning 19 CMV open reading frames selected because they previously correlated with total CMV-specific T-cell responses in healthy donors. Cells producing cytokines in response to pp65 or IE-1 together composed <12% and <40% of the total CD4(+) and CD8(+) T-cell responses to CMV, respectively. These proportions were generally similar regardless of HIV serostatus. Thus, analyses of total CMV-specific T-cell responses should extend beyond pp65 and IE-1 regardless of HIV serostatus.
Pharmacotherapy | 2006
Beulah P. Sabundayo; Julie H. McArthur; Susan Langan; Joel E. Gallant; Joseph B. Margolick
Study Objectives. To examine the frequency of highly active antiretroviral therapy (HAART) modifications, the reasons for these modifications, and toxicities of these drugs in patients receiving their first HAART regimen after a diagnosis of acute (< 2 mo from infection) or early (2–12 mo) human immunodeficiency virus (HIV) infection.
AIDS | 2010
Christine M. Durand; Karen A. O'Connell; Linda G. Apuzzo; Susan Langan; Hejab Imteyaz; Aima A. Ahonkhai; Christina M. Ceccato; Thomas M. Williams; Joseph B. Margolick; Joel N. Blankson
We studied viral evolution in five human leukocyte antigen (HLA)-B*57 patients recently infected with HIV-1. Escape mutations in HLA-B*57-restricted Gag epitopes were present at study entry in all patients, but were not associated with significant increases in viremia. Conversely, no new escape mutations in HLA-B*57-restricted epitopes or known compensatory mutations were detected in patients who experienced significant increases in viremia. Thus, the development of escape mutations alone does not determine virologic outcome in recently infected HLA-B*57 patients.
Journal of Acquired Immune Deficiency Syndromes | 2002
Carol Hilton; Beulah P. Sabundayo; Susan Langan; Martha Hilton; Charlamaine Henson; Thomas C. Quinn; Joseph B. Margolick; Kenrad E. Nelson
Objectives: To evaluate the effectiveness of urine screening to detect HIV‐infected individuals in high‐prevalence communities. Methods: Urine HIV testing was performed at 16 discrete events and four ongoing testing sites in Baltimore communities with a high incidence of HIV infection. When possible, positive urine test results were confirmed by blood testing. In addition, we attempted to obtain blood samples from subjects who reported a possible exposure to HIV but did not have a positive urine test. Results: From February 1998 to August 2001, we screened 1718 persons. Overall, 210 persons (12%) were HIV‐positive, of whom 169 (80%) had never previously tested positive; 87% of those who tested positive received their results, and most were referred for medical care. Conclusions: Urine‐based screening for HIV infection in high‐prevalence inner city communities can be an effective tool for identifying and treating infected persons who are unaware of their infection.
Psychosomatics | 2017
Sherita Hill Golden; Nina Shah; Mohammad Naqibuddin; Jennifer L. Payne; Felicia Hill-Briggs; Gary S. Wand; Nae Yuh Wang; Susan Langan; Constantine G. Lyketsos
OBJECTIVE To estimate the crude prevalence of minor depressive disorder (MinD) in a clinic-based population of adults with type 2 diabetes. METHODS We screened a clinical sample of 702 adults with type 2 diabetes for depressive symptoms using the Patient Health Questionnaire-2 and performed a structured diagnostic psychiatric interview on 52 screen-positive and a convenience sample of 51 screen-negative individuals. Depressive disorder diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and categorized as MinD, major depressive disorder (MDD), or no depressive disorder. We estimated prevalence of MinD and MDD and derived 95% CIs. RESULTS The crude prevalence of current, past, and current or past MinD was 4.3% (95% CI: 0.9-9.2%), 9.6% (95% CI: 3.9-15.9%), and 13.9% (95% CI: 7.7-21.2%), respectively. The crude prevalence of current, past, and current or past MDD was slightly higher-5.0% (95% CI: 1.9-9.4%), 12.0% (95% CI: 6.1-19.5%), and 17.0% (95% CI: 10.1-24.8%), respectively. There was a high prevalence of coexisting anxiety disorders in individuals with MinD (42.2%) and MDD (8.1%). Hemoglobin A1c levels were not significantly different in individuals with MinD or MDD compared to those without a depressive disorder. CONCLUSIONS MinD is comparably prevalent to MDD in patients with type 2 diabetes; both disorders are associated with concomitant anxiety disorders. MinD is not included in the DSM-5; however, our data support continuing to examine patients with chronic medical conditions for MinD.
AIDS | 2010
Joseph B. Margolick; Hejab Imteyaz; Joel E. Gallant; Susan Langan; Jason B. Dinoso; Janet D. Siliciano; Joel N. Blankson; Tricia L. Nilles; Kendall A. Smith; Linda G. Apuzzo
Interleukin (IL)-2 has been studied as a treatment for HIV infection because it stimulates the proliferation of T cells and augments antiviral immune functions [1,2]. Two regimens have been used: intermittent IL-2 (5 days every 8 weeks, usually 4.5–9 million international units (mIU)/day) and ultra-low-dose (ULD) IL-2 (1.2 mIU/m2/day), which can be given daily for weeks or months [1]. In patients with chronic and early/acute HIV infection, neither regimen has conferred any health benefit when given with concurrent antiretroviral therapy (ART) [3–7], and in patients with chronic HIV infection, ULD IL-2 did not improve viral control after stopping ART [8]. However, treatment of acute/early HIV infection with daily ULD IL-2 and interruption of ART has not been studied. We treated one patient who had taken ART since 1 month after HIV seroconversion with daily ULD IL-2. After receiving IL-2, this patient’s viral load set point off highly active antiretroviral therapy (HAART) was less than 50 copies/ml as compared with 39 000 copies/ml when ART was stopped without IL-2. Further, after IL-2 was stopped, viral load did not rebound for 14 months without ART. A 29-year-old man tested HIV-positive by ELISA and western blot 1.5 months after a negative ELISA, and was treated 30 days later with zidovudine, lamivudine, and efavirenz. Viral load was undetectable for 4 years on ART (with minor changes in regimen), except for occasional blips (all <900 copies/ml) (Fig. 1a). Fig. 1 Antiretroviral treatment, viral load, and immunological parameters in the patient He then entered a study to determine whether treatment with ULD IL-2 could lower the viral load set point in patients who began ART during very early HIV infection. As per protocol, he underwent two ART interruptions: the first prior to the use of IL-2 and the second 4.5months after daily IL-2 (Chiron, Inc., Charlotte, North Carolina, USA; 1.2mIU/M2/day subcutaneously, self-administered) was added to ART. After the second ART interruption, IL-2 monotherapy was continued for 1.5 months, and then all therapy was stopped. He was the only patient to complete this protocol. The study was approved by the local institutional review board, and informed consent was obtained. After the first ART interruption, viral load became detectable within 2 weeks to a set point of 39 000 (4.6 ± 0.3 log10) copies/ml (Fig. 1a). After the second ART interruption, viral load set point was below 50 (1.7 log10) copies/ml. Viral load remained undetectable for 14 months after all therapy was stopped (with one blip), then rebounded to approximately 5.0 log10 copies/ml; ART was restarted with resuppression of viral load to below 50 copies/ml. Five months after the second interruption of ART (3.5months off IL-2), viral load was 4 (0.6 log10) copies/ml by a specialized assay [9], and replication-competent HIV was present at 2.5 infectious units per million resting CD4 T cells using established procedures [10]. CD8 suppressor function against autologous HIV (assayed as described [11]) was weaker than that of an elite HIV controller studied simultaneously (data not shown). During IL-2 administration, serum IL-2 concentrations ranged from 15 to 18 pmol/l by ELISA (Quest Diagnostics, Madison, New Jersey, USA), concentrations which affect primarily high-affinity IL-2 receptors [1]; biologic effects included increases of five- to seven-fold in circulating eosinophils and natural killer cells and of five-to 20-fold in serum levels of several cytokines and chemokines [assessed by multiplex electrochemiluminescence (MSD, Gaithersburg, Maryland, USA; now Novartis International AG, Basel, Switzerland) on stored serum], including interferon-γ, IL-5, IL-10, IL-13, thymus and activation-regulated chemokine [chemokine (C–C motif) ligand (CCL)17], monocyte chemotactic protein (MCP)-1 (CCL2), MCP-4 (CCL13), IP10 (chemokine (C–X–C motif) ligand 10), and eotaxin-3 (CCL26) (data not shown). The CD4/CD8 ratio, which had almost always been less than 1, became consistently more than 1 (Fig. 1b). Thus, the cytokine milieu in vivo leading up to and following the second ART interruption was quite different from that surrounding the first ART interruption. After IL-2 was stopped, serum levels of cytokines and chemokines returned to pre-IL-2 levels. However, the CD4/CD8 ratio remained more than 1 until the second viral rebound 14 months later (Fig. 1b), and median absolute eosinophil and B-cell counts were significantly higher in the year following IL-2 administration than the year preceding it (for eosinophils, 80/µl vs. 50/µl, respectively, P = 0.003 by rank sum test; for B cells, 452/µl vs. 247/µl, respectively, P = 0.01). Tests for antiretroviral drug levels while viral load was undetectable following the second ART discontinuation were negative. The patient was human leukocyte antigen (HLA)-A*11, HLA-A*24, HLA-B*3503, HLA-B*400102 (TriCore Laboratories, Albuquerque, New Mexico, USA). To our knowledge, this is the only patient who has been treated with ULD IL-2 following years of viral suppression by ART initiated during very early HIV infection, and also the first reported case of spontaneous suppression of viral load to below 50 copies/ml for more than 2 months after a second ART interruption, in a patient whose viral load rebounded after the first interruption. In the study by Kaufman et al. [12], for example, all 11 such patients had detectable viral loads within 5 weeks of stopping HAART. It is striking that this unique response should be achieved in the only patient who has been treated with both early ART and subsequent daily ULD IL-2. Suppression of viral load to undetectable levels can occur in people who discontinue ART after starting it during early HIV infection [13], but this outcome is rare and may be unrelated to ART. This patient’s two viral load rebounds when HAART was interrupted demonstrate that he was not simply destined to maintain an undetectable viral load. Taken together, the data argue that ULD IL-2 enhanced anti-HIV immunity and viral suppression in this patient until the effects of IL-2 eventually abated. This interpretation is supported by the persistence of some of the effects of IL-2 in this patient, such as elevation in circulating eosinophils, circulating B cells, and the CD4/ CD8 ratio after IL-2 was stopped, and by findings in the mouse lymphocytic choriomeningitis virus model, in which administration of daily low-dose IL-2 for 1 week stimulated antiviral immunity for several months [2]. The possibility that this patient’s prolonged virological control after the second ART interruption was unrelated to ULD IL-2 therapy cannot be completely excluded [14]; nevertheless, it will be important to test the reproducibility of this putative effect of daily ULD IL-2, along with early initiation of ART, in additional patients. Moreover, understanding the mechanism of this patient’s prolonged viral suppression could be important in identifying targets for candidate vaccines and surrogate markers for vaccine efficacy. That the patient’s viral suppression was not permanent does not diminish the importance of these studies.
Journal of Diabetes and Its Complications | 2017
Na Shin; Felicia Hill-Briggs; Susan Langan; Jennifer L. Payne; Constantine G. Lyketsos; Sherita Hill Golden
AIMS We examined whether problem-solving and diabetes self-management behaviors differ by depression diagnosis - major depressive disorder (MDD) and minor depressive disorder (MinDD) - in adults with Type 2 diabetes (T2DM). METHODS We screened a clinical sample of 702 adults with T2DM for depression, identified 52 positive and a sample of 51 negative individuals, and performed a structured diagnostic psychiatric interview. MDD (n=24), MinDD (n=17), and no depression (n=62) were diagnosed using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria. Health Problem-Solving Scale (HPSS) and Summary of Diabetes Self-Care Activities (SDSCA) questionnaires determined problem-solving and T2DM self-management skills, respectively. We compared HPSS and SDSCA scores by depression diagnosis, adjusting for age, sex, race, and diabetes duration, using linear regression. RESULTS Total HPSS scores for MDD (β=-4.38; p<0.001) and MinDD (β=-2.77; p<0.01) were lower than no depression. Total SDSCA score for MDD (β=-10.1; p<0.01) was lower than for no depression, and was partially explained by total HPSS. CONCLUSION MinDD and MDD individuals with T2DM have impaired problem-solving ability. MDD individuals had impaired diabetes self-management, partially explained by impaired problem-solving. Future studies should assess problem-solving therapy to treat T2DM and MinDD and integrated problem-solving with diabetes self-management for those with T2DM and MDD.
Medical Hypotheses | 2014
Catherine N. Kibirige; Frederick A. Menendez; Hao Zhang; Tricia L. Nilles; Susan Langan; Joseph B. Margolick
The mechanisms involved in the decline of CD4 and CD8 T-cells that lead to HIV-induced immune dysregulation are not clearly understood. We hypothesize that late-emerging strains of HIV, such as CXCR4-tropic (X4) virions, induce T-cell homeostasis failure by promoting significantly more bystander cell death, and immune exhaustion in naïve CD4 and all CD8 T-cells, when compared to strain of HIV, such as CCR5-tropic (R5) virions, found early during the course of infection. In the reported study, inactivated X4 virions induced greater bystander cell death in sort-purified naïve CD4 T-cells compared to R5 virions, which was significant (p=0.013), and in memory CD8 T-cells, though the latter was not significant. A clearer understanding of the mechanisms involved in HIV-induced depletion of T-cell numbers and function could lead to therapies that prevent T-cell death and restore immune function. These therapies could improve current anti-retroviral and cure-related treatments by boosting the immune systems own ability to combat the virus.