Deficient Cell-mediated Immunity Research Articles

The Role of Cell-Mediated Immunity Deficiency in the Clinical Evolution of Patients with Tuberculosis Associated with HIV Infection

HIV infection induces severe immunosuppression, considered the major risk factor for tuberculosis (TB). Objective — to evaluate the clinical characteristics of patients with TB-HIV co-infection based on the level of immune deficiency to establish recommendations for improving clinical case management. Materials and methods. A prospective, selective study included 86 TB patients, divided into the study group with 38 cases of TB evolved into acquired immunodeficiency syndrome (AIDS), established with a CD4+ level ≤ 200/μL and the control group with 48 TB cases having CD4+ ≥ 200/μL. Results and discussion. The study assessed the impact of the severity of the cell mediated immune deficiency associated with HIV infection on the clinical evolution of TB and the final therapeutic outcome. Laboratory indicators characterizing TB in AIDS included general leukocytosis, lymphocytopenia, eosino­philia, anemia and, in rare cases, thrombocytopenia. All AIDS patients were untreated with ARV, and only one-third were in the early stages of symptomatic HIV infection. Risk factors for TB in AIDS included rural residence, low education levels and mental disorders. Treatment success was low, and the death rate was high in both groups, emphasizing the impact of associated conditions. Despite differences in the serum level of CD4+ cells, the rate of therapeutic success was equally low in both groups, with one-third continuing antituberculosis treatment. The death rate was insignificantly higher in the TB on AIDS group (23.4 %) vs. 18.7 % in early HIV stages due to comorbidities associated with HIV infection. Conclusions. The study identified risk factors for TB in patients diagnosed with AIDS stage of symptomatic HIV infection, including residence in rural areas, low education levels and mental and behavioral disorders associated with multiple causes such as alcohol consumption, drug use and toxoplasmosis of the central nervous system. Recommendations include complex screening for TB and HIV in all socially vulnerable groups, reinforced by primary prevention and an individualized therapeutic approach.

Brain abscess nocardiosis: case report

Nocardiosis is an infection caused by Nocardia species, that are filamentous aerobic Gram-positive bacilli that belong to Actinomycetaceae family, it can cause a localized or a disseminated infection. Pulmonary disease is the most common presentation of nocardiosis in immunosuppressed patients and approximately one-third have a disseminated disease, that happens when lesions are found at two or more locations in the body. Nocardial brain abscesses are a rare central nervous system infection but has been highlighted as a differential diagnosis of brain tumors, due to the increase of the infection in deficient cell-mediated immunity patients. Even though nocardiosis represents only 2% of brain abscesses, it is an illness associated with significant mortality, present on 75% to 90% of cases. We present a case of central nervous system nocardiosis in a 59-year-old patient with a previous history of diabetes mellitus and alcoholic liver disease. The patient sought the emergency department with temporal occipital headache and mental confusion for 3 days. Imaging tests were performed that showed an oval lesion in the temporoparietooccipital region. Nocardiosis in the central nervous system was hypothesized and treatment was initiated. Despite medical support, the patient died. The lesion material was collected in which nocardiosis was diagnosed when analyzed histochemically.

Case report of pulmonary nocardiosis in a patient of right renal transplantation

Nocardiosis results from infection with bacteria of genus Nocardia, which are saprophytic aerobic actinomycetes that commonly reside in soil relatively and are inactive on standard biochemical tests. Pulmonary and systemic nocardiosis is common in adult males, almost all being sporadic, common in tuberculosis endemic regions and usually seen in individuals with deficient cell mediated immunity. It may present as pneumonia, empyema, pericarditis, mediastinitis, laryngitis, peritonitis, and meningitis. Diagnosed with sputum or pus for branching beaded gram positive filaments which are 1 micron meter wide and 50 micron meter long.A male immunocompromised patient presented with respiratory symptoms. Patient was evaluated elsewhere and received multiple courses of antibiotics. On admission in our facility HRCT thorax followed by fibre optic bronchoscopy was done. Bronchoalveolar lavage was sent for microbiological analysis. Acid-fast in kinyoun and Ziehl Neelsen stain came positive for Nocardia and was managed with trimethoprim- sulfamethoxazole which is the treatment of choice.

Nonpruritic hypopigmented macules on an immunocompromised patient

Nonpruritic hypopigmented macules on an immunocompromised patient

Miliary tuberculosis presenting with acute respiratory distress syndrome in a patient with down syndrome

Introduction. Miliary tuberculosis (TB) is a rare and potentially fatal form of disseminated TB. It is caused by a widespread haematogenous dissemination of Mycobacterium tuberculosis from an active caseous focus to different organs. Sometimes it can have an acute presentation with a rapidonset clinical deterioration and death. Miliary TB complicated with an acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) is rare, even in countries with a high incidence of TB. Case report. A 35-yearold woman with Down syndrome (DS) was admitted to the Clinic for Pulmonology, Clinical Centre Kragujevac, due to an evaluation of cough and weight loss during last 2 months. Laboratory findings revealed anaemia, leukocytosis, elevated C-reactive protein (CRP) and hypoalbuminemia. A chest x-ray showed bilateral reticulonodular shadows, predominantly in the mid and lower right lung lobes. A purified protein derivative (PPD) skin test and induced sputum smear for acid-fast bacilli (AFB) were both negative. On the fifth day following admission, her health condition suddenly declined, and after developing a moderate ARDS, she was put on the mechanical ventilation. Due to a high clinical suspicion of miliary TB and the fact that her life was compromised, an empirical anti-tuberculosis therapy was initiated. Despite all therapeutic and supportive measures, the patient expired 3 days later. The diagnosis of miliary TB was established post-mortem. Conclusion. Miliary TB should be kept in mind in patients with DS due to immunosuppression associated with deficient cell-mediated immunity. The development of ARDS as a complication of miliary TB is difficult to identify due to a low causal association. High clinical suspicion and a chest radiograph with a typical appearance of miliary pattern justify the initiation of empirical anti-tuberculosis treatment in such patients, as an attempt to change poor prognosis.

Pneumocystis pneumonia in HIV-1-infected patients.

Pneumocystis pneumonia (PCP) is an opportunistic disease that mainly affects patients with a deficiency of cell-mediated immunity, especially acquired immunodeficiency syndrome (AIDS). The incidence of PCP in these patients has declined substantially owing to the widespread use of antiretroviral therapy and PCP prophylaxis. However, PCP is still a major AIDS-related opportunistic infection, particularly in patients with advanced immunosuppression in whom human immunodeficiency virus type 1 (HIV-1) infection remains undiagnosed or untreated. The clinical manifestations, diagnosis, treatment, and prevention of PCP in patients with HIV-1 infection are addressed in this review.

Molecular detection of Toxoplasma gondii in a sample of Iraqi patients with acute leukemia and Stem cell transplantation

Acute leukemia is the most common hematological malignancies; the malignant cells are immature cells that areincapable of performing their immune system functions. Chemotherapy and Hematopoietic stem cell transplantation (HSCT) are the established treatment for a variety of malignant diseases including acute leukemia. After induction chemotherapy and allogeneic bone marrow transplantation there will be suppression of the immunity and the patients will be susceptible for many opportunistic infections or reactivation of latent infections. Opportunistic infections of T.gondii make an important threat to patients with acute leukemia after the use of intense chemotherapy and immunosuppression drugs following allogeneic HSCT. To detection of T.gondiiin patients with acute leukemia after chemotherapy (induction) courses and post allogeneic Stem cell transplantation patients within the first year and determine copy number of T.gondiiin these groups and compare with apparently healthy individual as control group.A prospective study enrolled 61 patients who diagnosed to have acute leukemia. Forty eight of them had received an induction course of chemotherapy, within one month of diagnosis (group I). While the other 13 acute leukemia patients had assessed after bone marrow transplantation within the first year of diagnosis as group II and 30 apparently healthy individuals as control group. The questionnaire form was given to each patient included: age, sex, residence, Job, Virology screen (HBV,HCV),type of acute leukemia,Chronic disease (DM or HT) if present,frequency of Blood transfusion in addition to CBC. Blood samples were collected from all groups. T. gondii DNA was extracted from 1 ml whole blood samples,and then,T. gondii DNA was detected and measured by Taqman quantitative real-time PCR.The serum to measure IgG and IgM antibody specific to T. gondii wasinvestigated in the control group by an enzyme-linked immune assay (ELISA).T. gondii parasitemia was detected in (8.3%) 4 out of 48 group I patient. While negative in group II and control group. The range of T.gondii load was(6.285×103-17.915×103) copy/ml,the mean of the copy numbers 11458.75± 5120.85.The study is of medical importance as it deals with immunocompromised patients,notably those with cell mediated immunity deficiency who are at risk for life threatening opportunistic infections or reactivation,T.gondii should be looked for Leukemic patients at least by routine serological test for early diagnosis and proper treatment of the patient may reduce the complications of infection and promote better prognosis. And Quantitative PCR is used to monitor PBMT patients at risk for T.gondii disease and for a timely start of preemptive therapy.

A Study of the Changes of T Helper 17 Cells and Regulatory T Cells in Herpes Zoster.

BackgroundImmunosuppression and age-related deficiencies in cell-mediated immunity are important factors for the reactivation of latent varicella-zoster virus (VZV). CD4+CD25+Foxp3+ regulatory T (Treg) cells and T helper 17 (Th17) cells are closely associated with various viral infections.ObjectiveWe analyzed Treg cells and Th17 cells in patients with herpes zoster and investigated their relationship with the reactivation of latent VZV.MethodsTreg and Th17 cells in peripheral blood and the ratio of Th17 to Treg cells were examined in patients with herpes zoster and healthy controls. Changes between pre-treatment and post-treatment estimates of Treg and Th17 cells and clinical parameters in patients with herpes zoster were also analyzed.ResultsThe proportion of circulating Th17 cells and the Th17/Treg cell ratio were significantly higher in patients with herpes zoster than controls (p=0.012, 0.013), but there was no significant difference in the proportion of Treg cells between groups. There was no significant difference in the proportions of Treg and Th17 cells and the Th17/Treg cell ratio before and after treatment and between the non-postherpetic neuralgia and postherpetic neuralgia groups. Changes in Treg and Th17 cells and the Th17/Treg cell ratio were not significantly correlated with changes in the visual analog scale. Body surface area was significantly correlated with Treg cells, Th17 cells, and the Th17/Treg cell ratio (p=0.022, 0.002, 0.004).ConclusionAn imbalance between Th17 and Treg cells is associated with the reactivation of VZV, which may contribute to pathogenesis of herpes zoster.

Inosine Acedoben Dimepranol promotes an early and sustained increase in the natural killer cell component of circulating lymphocytes: A clinical trial supporting anti-viral indications

Inosine Acedoben Dimepranol (IAD), licensed for the treatment of cell-mediated immune deficiencies associated with viral infections, has been reported to impact a variety of immune parameters both in vitro and in vivo. Here we report the results from a clinical trial where multiple lymphocyte subsets – CD19+ B cells, CD3+ T cells, CD4+ T-helper cells, FoxP3hi/CD25hi/CD127lo regulatory T cells (Tregs), CD3−/CD56+ NK cells, and CD3+/CD56+ NKT cells – were, together with serum immunoglobulins and IgG subclasses, followed during 14days of IAD administration to ten healthy volunteers; these selected from 27 individuals pre-screened in vitro for their capacity to respond to IAD as gauged by increases in the percentage of Treg and/or NKT cells arising in PHA-stimulated cultures. While a transient spike and dip in Treg and T-helper fractions, respectively, was noted, the outstanding consequence of IAD administration (1g po, qds) was an early and durable rise in NK cells. For half the cohort, NK cells increased as a percentage of total peripheral blood lymphocytes within 1.5h of receiving drug. By Day 5, all but one of the volunteers displayed higher NK cell percentages, such elevation – effectively a doubling or greater – being maintained at termination of study. The IAD-induced populations were as replete in Granzyme A and Perforin as basal NK cells. The novel finding of IAD boosting phenotypically competent NK numbers in healthy individuals supports the drug's indicated benefit in conditions associated with viral infection and reinforces the potential for uplift where immune performance may be compromised.

Disseminated nocardiosis after unrelated bone marrow transplantation

Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity. Although disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a rare complication, it is associated with high mortality. Moreover, after allo-HSCT, nocardiosis may be mistaken for other bacterial or fungal infections because clinical and radiographic findings of pulmonary, cerebral, and cutaneous nocardiosis lesions are non-specific. Here, we report a case of disseminated nocardiosis (caused by Nocardia abscessus) with skin, pulmonary, liver, lymph node, and multiple brain abscesses in a patient after allo-HSCT. The patient initially responded clinically and radiographically to imipenem/cilastin and trimethoprim-sulfamethoxazole therapy. Clinicians should be aware of the possibility of nocardiosis in allo-HSCT recipients who are treated with multiple immunosuppressive agents to control chronic graft-versus-host disease. Accurate diagnosis and identification of disseminated nocardiosis is important to ensure administration of the correct antibiotic regimen.

Abstract 3443: Associations of immune-related conditions with squamous cell and basal cell skin cancer risk

Abstract Elevated risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin has been identified in a number of clinical populations with conditions affecting the immune system, such as organ transplant recipients and non-Hodgkin lymphoma patients. However, because many other immune-related conditions are rare, their relationships with SCC and BCC have not been studied. We used Medicare claims to identify SCC and BCC cases in 2012 and to select controls in 2012 matched on sex and age with a 10:1 ratio. All subjects were of white race. For cases and controls, we used Medicare claims during 1999-2011 to identify 44 immune-related conditions (immunosuppressive conditions, autoimmune diseases, hematologic malignancies, and allergic diseases). The statistical significance of associations was determined after Bonferroni correction for multiple comparisons. In Medicare in 2012, there were a total of 470,756 SCC and 601,863 BCC cases. Of the 44 immune-related conditions included, SCC was associated with 41 (93%) and BCC was associated with 31 (70%). For most conditions, SCC was more strongly associated than BCC. We identified significant associations of SCC and BCC risk with well-characterized conditions, such as HIV, rheumatoid arthritis, and allergic rhinitis (SCC odds ratios (ORs) of 1.64, 1.29, and 1.29, respectively; BCC ORs of 1.60, 1.10, and 1.22; Table), as well as with poorly characterized or rare conditions, such as deficiency of cell-mediated immunity and polyarteritis nodosa (SCC ORs of 2.87 and 1.92; BCC ORs of 1.55 and 1.49). In conclusion, most immune-related conditions in our study indicated an elevated risk of non-melanoma skin cancer, particularly SCC. These findings provide evidence that immune dysfunction, as manifest across a wide range of conditions, may play an important role in development of SCC and BCC. Possible mechanisms could include direct effects of immune-related conditions or their treatments. Results from a sample of the immune-related conditions assessedSquamous cell carcinomaBasal cell carcinomaImmune-related conditionsN cases (%)OR95% CIp-valueN cases (%)OR95% CIp-valueTotal470756601863Immunosuppressive conditionsDeficiency of humoral immunity1550 (0.33)2.552.41-2.69<1E-200*1426 (0.24)1.821.72-1.937.1E-99*HIV276 (0.06)1.641.44-1.861.6E-14*366 (0.06)1.601.43-1.784.8E-17*Deficiency of cell-mediated immunity53 (0.01)2.872.11-3.891.5E-12*37 (0.01)1.551.10-2.190.013Autoimmune diseasesRheumatoid arthritis15754 (3.4)1.291.26-1.318.2E-188*16893 (2.8)1.101.09-1.123.7E-33*Pernicious anemia10792 (2.3)1.131.11-1.159.8E-33*11218 (1.9)1.000.98-1.020.90Psoriasis9765 (2.1)1.551.52-1.59<1E-200*9812 (1.6)1.231.20-1.252.0E-79*Polymyalgia rheumatica8567 (1.8)1.281.25-1.316.4E-102*9623 (1.6)1.231.20-1.255.1E-78*Ulcerative colitis3807 (0.81)1.301.26-1.351.5E-52*4524 (0.75)1.251.21-1.293.7E-44*Crohn's disease3121 (0.66)1.641.58-1.714.8E-148*3226 (0.54)1.361.31-1.411.5E-61*Hematologic malignancies and related conditionsNon-Hodgkin lymphoma15165 (3.2)2.252.21-2.29<1E-200*13834 (2.3)1.651.62-1.68<1E-200*Paraproteinemia & related disorders4876 (1.0)1.571.52-1.621.1E-189*5312 (0.88)1.421.38-1.466.5E-128*Aplastic anemia3756 (0.80)1.511.46-1.569.2E-124*3433 (0.57)1.141.10-1.181.7E-13*Multiple myeloma2050 (0.44)1.661.58-1.744.0E-102*1865 (0.31)1.221.17-1.282.4E-16*Leukemia1370 (0.29)1.921.81-2.044.5E-112*1235 (0.21)1.371.29-1.453.5E-25*Allergic diseasesAllergic rhinitis53334 (11)1.291.28-1.30<1E-200*63566 (11)1.221.21-1.23<1E-200*Asthma38871 (8.3)1.131.12-1.141.3E-106*44180 (7.3)1.021.01-1.032.3E-05*Atopic dermatitis/eczema4338 (0.92)1.551.50-1.601.7E-160*4185 (0.70)1.221.18-1.261.7E-33**Associations were statistically significant at a Bonferroni adjusted alpha level of 0.000568 ( = 0.05/88 statistical tests). Citation Format: Elizabeth L. Yanik, Ruth M. Pfeiffer, D. Michal Freedman, Eric A. Engels. Associations of immune-related conditions with squamous cell and basal cell skin cancer risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3443.

Third-Party Virus-Specific T Cells (VST) Are Efficacious in the Treatment of Refractory Infection Post-HSCT, However Other Cell-Mediated Immune Deficiencies Appear to Persist

Third-Party Virus-Specific T Cells (VST) Are Efficacious in the Treatment of Refractory Infection Post-HSCT, However Other Cell-Mediated Immune Deficiencies Appear to Persist

Nocardial Paraspinal Abscess in a Renal Transplant Recipient: Defying Timelines and Clinical Presentation-Masquerading as Acute Disc Prolapse-A Rare Case

Nocardia is an aerobic gram-positive filamentous branching bacterium. It causes infections which results either from trauma-related introduction of the organism or from inhalation resulting in a pulmonary focus particularly in immune compromised patients. Systemic nocardiosis occurs in patients with deficient cell-mediated immunity, such as patients with haematopoietic malignancies, Human Immunodeficiency Virus infection and organ transplant recipients on immunosuppressive drugs. Though nocardiosis presents as paraspinal abscess in renal transplant recipients, we report a patient who presented as acute low back ache and was diagnosed as having acute disc prolapse and referred for orthopaedic consultation.

Immuno-reactivity of excised lymph nodes in neck dissections of squamous cell carcinomas of oral cavity

Background:Regional lymph nodes play an important role in acting as anatomic barriers to systemic dissemination of tumor cells. This reflects in the host immunologic response. Oral squamous cell carcinoma, is known to be associated with early deficiencies of cell-mediated immunity, the pathology of which is reflected in the histology of the regional lymph nodes.Aim:The goal of this study was to study the different immunity reactions in the lymph nodes and to correlate it with the histopathology of tumor proper.Materials and Methods:Out of 40 head and neck dissections, 30 were male and 10 females within the age range of 21–72 years. According to Tumor Node Metastasis classification, there were 12 cases of stage II and stage III, respectively while 16 were of stage IV. A total of 372 nodes were histologically evaluated. The harvested lymph nodes were categorized into metastatic and non-metastatic nodes exhibiting four patterns as: Lymphocyte predominance pattern, germinal center predominance pattern, lymphocyte depleted pattern and unstimulated pattern.Results:The predominant pattern of lymph node reactivity was of lymphocyte predominance (199 nodes) followed by germinal center predominance (117 nodes); lymphocyte depleted (17 nodes) and unstimulated node pattern (39 nodes). Twenty-seven nodes were positive for metastasis. A statistically significant relationship (P = 0.0019 and P = 0.0290, chi square, respectively) was observed between the number of nodes harvested and stage and level of lymph nodes. A brief follow-up period of 3 years was carried out.Conclusion:Further studies relating the immuno-morphologic assessment of the lymph nodes in conjunction with other factors may be helpful in assessing the metastases risk of the individual.

Pneumocystis Jirovecii Pneumonia (PCP) in Children with Cancer: A Retrospective Cohort Analysis from the Pediatric Health Information System (PHIS) Database, 2004-2009

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection that can develop in the setting of deficient cell-mediated immunity. Children with hematologic malignancies and children undergoing immunosuppressive treatment for other types of cancer are at risk of developing PCP. However, the epidemiology of PCP in children with cancer is not well described. We sought to determine the prevalence of PCP in hospitalized children with cancer in the U.S. and to identify risk factors for PCP in this population.Methods: This retrospective cohort study included pediatric patients with newly diagnosed cancer at 45 children’s hospitals in the U.S. between January 1, 2004, and December 31, 2009. Data was obtained from the Pediatric Health Information System (PHIS). Patients were included if they were 0 to 20 years of age and had an index hospitalization with an ICD-9 diagnosis code for a malignant condition (140 to 239.39). Patients who had a benign tumor, >1 cancer type, or non-specific cancer codes, and those who received a hematopoietic stem cell transplant were excluded. Groups were defined for cancer types by ICD-9 codes: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), Hodgkin disease (HD), central nervous system (CNS), and solid non-CNS tumors. Patients within the cohort who had a diagnosis of PCP (ICD-9 code 136.3) within 3 years of their cancer diagnosis were considered PCP cases. The relative risk for PCP was calculated according to demographics and cancer types. The data were analyzed for trends in the incidence of PCP cases by year, the time to PCP diagnosis following cancer diagnosis, and the regional distribution of PCP in the U.S.Results: A total of 33,067 pediatric cancer patients met the criteria for inclusion in the study. Of these patients, 169 (0.5%) were classified as PCP cases (Table 1). Patients with ALL and AML had the highest relative risks of PCP, when compared with other cancer types. Patients of Asian race had the highest relative risk of PCP, when compared with patients of other races. [Display omitted] Figure 1 depicts that the time to the development of PCP was relatively short in patients with NHL (median 33 days, IQR: 0-253 days) and AML (median 70 days, IQR: 0-149 days). In contrast, PCP was diagnosed later in patients with ALL, (median 347 days, IQR; 168-675 days). The number of new PCP cases did not significantly vary by year of diagnosis. Regional differences in the diagnosis of PCP by the locations of PHIS institutions were not identified. [Display omitted] Conclusions: This study represents the largest cohort analysis of PCP in children with cancer. Among children with cancer who were hospitalized at major U.S. children’s hospitals during the study period, the prevalence of PCP was 0.5%. The relative risk of PCP was increased in patients with leukemia when compared with other cancer types. However, PCP was identified in all cancer types. The variation in time to diagnosis of PCP is hypothesized to be due to differences in the intensity and duration of immunosuppressive therapy by cancer type. DisclosuresNo relevant conflicts of interest to declare.

EL5 - Infections in Cancer Patients

Cancer patients are in immunocompromised states. Several background factors are necessary to be understood to know why these patients have been in immunocompromised states. Skin and mucosal barriers form the first line of defense against microbial invasion. Decreases in the neutrophil count in the peripheral blood increments the risk for infection. Cell-mediated immune deficiency are seen in hematopoietic stem cell transplant patients, lymphatic disorders like acute lymphocytic leukemia and malignant lymphoma. Humoral immune deficiency includes asplenia, splenic insufficiency, abnormal number or defective quality of immunoglobulin, and reduced complement production, etc.It is difficult to identify the infected organ in immune deficient patients. However, there are certain rules one can follow to narrow down the focus to a smaller number of possible organs. For instance, infections in patients with febrile neutropenia tend to present with a few symptoms and findings. Pyelonephritis may present without pyuria, and meningitis may only present with altered mental status without symptom of meningeal irritation or the CFS tests findings may not show elevated white blood cell count.For the treatment of infection in cancer patients, one point of note is to use the patient's history to efficiently narrow down and identify the pathogenic microbe. Observation is also extremely important, as well as the interpretation of the patient's condition, and the reason why he/she does not show signs of improvement.In my presentation I will discuss such “actual” cases.

Diagnosis and management of nocardiosis after bone marrow stem cell transplantation in adults: Lack of lymphocyte recovery as a major contributing factor

Hematopoietic cell transplantation (HCT) is a curative treatment for hematological malignancies. This therapeutic approach is associated with a profound immune deficiency and an increased rate of opportunistic infections. Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity, such as AIDS patients or transplant recipients. Diagnosis of nocardiosis can be challenging, as signs and symptoms are non-specific. Routine prophylaxis with trimethoprin/sulfamethoxazole (TMP/SMZ) does not prevent the risk of infection. Between May 2001 and December 2009, five cases of nocardiosis were diagnosed from the 366 allogeneic HCT recipients in our centre. Four patients developed a disseminated nocardiosis within the first year after HCT. The fifth patient presented a localized cutaneous nocardiosis. In disseminated cases, median total CD4+ T-cells were below 100cells/μL. Naive CD4+ CD45RA+/RO− T-cells were almost undetectable. CD8+ T-cells and NK cells were below the normal range and CD19+ B-cell reconstitution was completely deficient. In a localized case, we observed a lack of naive thymic emigrants CD4+ CD45RA+/RO− T-cells.

Meningoencefalitis por Nocardia spp.: Reporte de un caso y revisión de la literatura

La nocardiosis es una rara infección oportunista que afecta principalmente a pacientes con alteración de la inmunidad celular, como pacientes con síndrome de inmunodeficiencia adquirida o postrasplantes. El compromiso del sistema nervioso central es generalmente como absceso y menos frecuentemente como meningitis primaria. El presente artículo hace el reporte de un caso de meningitis primaria por Nocardia en paciente inmunocompetente y revisión de la literatura. Nocardiosis is a rare opportunistic disease that affects mainly patients with deficient cell-mediated immunity, such as those with acquired immunodeficiency syndrome (AIDS) or transplant recipients. The central nervous system presentation is as cerebral abscesses and less frequently, as primary meningitis. Here, a case of primary nocardia meningitis is described in a patient without a predisposing condition, along with a literature review.

Candida Vaginitis: When Opportunism Knocks, the Host Responds

Candida Vaginitis: When Opportunism Knocks, the Host Responds

Letter to the Editor Natural killer cell-mediated immune deficiency or compromise in patients with portopulmonary hypertension

Portopulmonary hypertension (POPH) is a form of pulmonary arterial hypertension (PAH) in the setting of portal hypertension, and is associated with a poor prognosis [1]. The underling etiological cause of POPH is poorly understood [1]. Previously we have reported T cell-mediated immune deficiency or compromise in patients with chronic thromboembolic pulmonary hypertension (CTEPH), idiopathic pulmonary hypertension (IPH), and acute pulmonary embolism (APE) [2, 3]. Here we report natural killer cell-mediated immune deficiency or compromise in patients with POPH. Nine patients (4 male, 5 female) diagnosed with POPH in Shanghai Tongji Hospital from year 2010 to 2011 were recruited in the present study, with a mean age of 65 ±19 years (30–82 years). The diagnosis of POPH is based on the hemodynamic criteria including portal hypertension and/or liver disease (clinical diagnosis) [4], pulmonary artery systolic pressure > 40 mm Hg at rest, pulmonary vascular resistance > 240 dynes × s × cm−5, and pulmonary artery occlusion pressure 12 [1]. We firstly detected the cluster of differentiation (CD) on the T cell surface. To our surprise, unlike the changes we previously reported in CTEPH, IPH, or APE, only slight changes of CD3+, CD4+ or CD8+ T cells were observed in POPH patients (Table I and Figures 1A–C). Interestingly, the number of CD16+CD56, which reflects the function of natural killer cell, was decreased in five patients with POPH (55.6%) (Table I and Figure 1D) [5]. Figure 1 Changes of T and NK cells of the patients enrolled in this study Table I The etiology, Child-Pugh Class, pulmonary artery systolic pressure, and the clusters of differentiation on T and NK cells of the patients enrolled in this study T cell-mediated immune deficiency or compromise has been reported in patients with CTEPH, IPH, and APE [2, 3]. In the present study, we failed to detect obvious cell-mediated immune changes. Natural killer cells, accounting for 15% of peripheral blood lymphocytes, are well-known unique effectors of the innate immune system as they can recognize stressed cells in the absence of antibodies and MHC [3]. As the role of natural killer cells is analogous to that of cytotoxic T cells [5], we detected their surface markers CD16 (FcγRIII) and CD56 in POPH patients and identified a natural killer cell-mediated immune deficiency or compromise in patients with POPH. Immune deficiency or compromise of natural killer cells is usually caused by virus infection, cancer, or immunosuppressive drugs [5]. In this study, malignant tumors or use of immunosuppressive drugs were excluded in these 9 patients; therefore the immune deficiency or compromise of natural killer cells is most likely due to virus infection. Our study indicated that the virus-killing function of natural killer cells is compromised in patients with POPH. The POPH might be a disease of acquired natural killer cell-mediated immune deficiency, and virus infection may be an important etiological factor of POPH. We also speculate that the pathogenic virus infection in POPH patients may be different from those in CTEPH, IPH, and APE.