Defects In Cell-mediated Immunity Research Articles

A 28-YEAR-OLD FEMALE WITH RIGHT UPPER LOBE MASS

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Nocardia represents a prevalent pathogen associated with high morbidity and mortality in the immunocompromised. Nocardiosis has been increasing in incidence in the U.S. with 500-1000 annual cases. Here, we present a 28-year-old female with SLE who presents with a lung mass. CASE PRESENTATION: A 28-year-old female with significant history of SLE with cardiorenal involvement on immunosuppressive agents, pulmonary hypertension and end stage renal disease on hemodialysis who presents with productive cough, dyspnea, fever, weight loss, and rash. Vital signs were temperature of 39.3°C, heart rate of 122 beats/min, blood pressure of 150/97 mmHg, respiratory rate of 24 breaths/min, and 100% oxygen saturation on nasal cannula 2 liters. Physical exam was significant for a systolic murmur radiating to axilla, decreased and coarse breath sounds bilaterally, raised centrally indented vesicular, non-erythematous rash located over right medial thigh. Labs were significant for positive ANA and anti-double stranded-DNA, leukocytosis, proteinuria, and negative cultures. Chest X-ray noted a right upper lobe peri-hilar mass. CT Thorax showed a right loculated pleural effusion, and a right upper lobe mass. Patient was started on intravenous steroids, empiric antibiotics and antivirals. CT guided percutaneous biopsy of right upper lobe anterior mass showed filamentous bacteria which finalized as N. farscinica and patient was started on linezolid due to trimethoprim-sulfamethoxazole (TMP-SMX) resistance and allergy. MRI brain was negative for dissemination. Patient was discharged on acyclovir for a herpetic rash, and linezolid for Nocardiosis. Upon follow-up, patient was switched to intravenous antibiotics due to intolerance to linezolid. DISCUSSION: N. farscinica most commonly affects the lung with half of cases disseminating to the brain. A major virulence factor is resistance to phagocytosis. Risk factors are defective cell-mediated immunity, diabetes, alcoholism and chronic lung disease. Radiographic findings can be lung masses, consolidation, pleural effusion, or nodules usually in upper lobes. In immunocompromised patients, TMP-SMX or intravenous amikacin, imipenem, meropenem, and linezolid are agents that can be used for management for at least 12 months. CONCLUSIONS: Nocardia is ubiquitous, but remains an under-diagnosed pathogen that is overlooked in the work up for lung masses in the immunocompromised. The non-specific clinical presentation, lack of available diagnostic testing coupled with poor yield from cultures and variable radiographic findings is what makes Nocardiosis a diagnostic dilemma. Reference #1: Wilson, J. (2012). Nocardiosis: Updates and Clinical Overview. Mayo Clinic Proceedings, 87(4), pp.403-407. Reference #2: Lerner P. Nocardiosis. Clinical Infectious Diseases. 1996;22:891-905 Reference #3: Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ, Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19:259-282. DISCLOSURES: No relevant relationships by Ali Chaudhry, source=Web Response No relevant relationships by Wael Nasser, source=Web Response No relevant relationships by Sachin Patel, source=Web Response

Toward T Cell-Mediated Control or Elimination of HIV Reservoirs: Lessons From Cancer Immunology.

As the AIDS epidemic unfolded, the appearance of opportunistic infections in at-risk persons provided clues to the underlying problem: a dramatic defect in cell-mediated immunity associated with infection and depletion of CD4+ T lymphocytes. Moreover, the emergence of HIV-associated malignancies in these same individuals was a clear indication of the significant role effective cellular immunity plays in combating cancers. As research in the HIV field progressed, advances included the first demonstration of the role of PD-1 in human T cell exhaustion, and the development of gene-modified T cell therapies, including chimeric antigen receptor (CAR) T cells. In the intervening years, the oncology field has capitalized on these advances, effectively mobilizing the cellular immune response to achieve immune-mediated remission or cure of previously intractable cancers. Although similar therapeutic advances have not yet been achieved in the HIV field, spontaneous CD8+ T cell mediated remission or functional cure of HIV infection does occur in very small subset of individuals in the absence of anti-retroviral therapy (ART). This has many similarities to the CD8+ T cell mediated functional control or elimination of cancers, and indicates that immunotherapy for HIV is a rational goal. In HIV infection, one major barrier to successful immunotherapy is the small, persistent population of infected CD4+ T cells, the viral reservoir, which evades pharmacological and immune-mediated clearance, and is largely maintained in secondary lymphoid tissues at sites where CD8+ T cells have limited access and/or function. The reservoir-enriched lymphoid microenvironment bears a striking resemblance to the tumor microenvironment of many solid tumors–namely high levels of anti-inflammatory cytokines, expression of co-inhibitory receptors, and physical exclusion of immune effector cells. Here, we review the parallels between CD8+ T cell-mediated immune control of HIV and cancer, and how advances in cancer immunotherapy may provide insights to direct the development of effective HIV cure strategies. Specifically, understanding the impact of the tissue microenvironment on T cell function and development of CAR T cells and therapeutic vaccines deserve robust attention on the path toward a CD8+ T cell mediated cure of HIV infection.

Evaluation of serum interleukin 17 and zinc levels in recalcitrant viral wart.

Warts are benign epithelial proliferations of the skin and mucosa caused by infection with HPV. Low IL-17 levels may contribute in occurrence, maintenance, severity, and recurrence of different types of cutaneous wart that depend mainly on the cell-mediated immunity defect. In a majority of the patients, zinc deficiency was associated with persistent, progressive, or recurrent viral warts. A careful dose of oral zinc sulfate may be helpful in the management of such patients. Zn deficiency negatively affects the Th17 cells. IL 6 induced STAT3 activation during chronic inflammation and Th17 development suppressed by Zn via attenuating this activation critically controls Th17-cell development. To evaluate the role of interleukin 17 and zinc in recalcitrant warts. All studied patients were subjected to history taking and dermatological examination. The evaluation of serum IL-17 level was done by ELISA in 25 recalcitrant wart patients and 25 wart patients. The measurement of serum zinc level was determined by colorimetric methods, using Au 480 Beckman coulter chemistry analyzer. The results revealed a significant decrease in serum IL-17 and zinc levels in recalcitrant wart patients. Both IL-17 and zinc deficiency have a role in the pathogenesis of recalcitrant warts through the imbalance of immune system and deficiency of immune cells. There is no significant correlation between serum levels of IL-17 and zinc, suggesting that they have different mechanisms in affecting the immune system.

Absolute lymphocyte count (ALC) as predictor of Pneumocystis Jiroveci Pneumonia (PCP) infection in patients on immune checkpoint inhibitors (ICPi).

e14255 Background: Checkpoint inhibitor pneumonitis (CIP) is an uncommon but serious immune related adverse event needing treatment with prolonged steroids. PCP prophylaxis is recommended for patients on daily prednisone equivalents of 20 mg or greater for at least 1 month. Known risk factors for PCP infection in general population are glucocorticoid use and defects in cell-mediated immunity. We conducted a retrospective study to evaluate the association between ALC and development PCP infection in the patients with CIP treated with steroids. Methods: A retrospective analysis of subjects who received ICPi for any type of cancer from 2011 to 2018 at a single institution was conducted. PCP was diagnosed by PCR of bronchioalveolar lavage. In patients with CIP, ALC at the beginning of steroid treatment, dose and duration of steroids and development of PCP infection was recorded. The median ALC was compared between the patients with PCP infection and without PCP infection via Welch’s t- test at 5% alpha. Results: Out of 515 patients who received ICPi, there were 429 (83.3%) Caucasians, 79(15.3%) African Americans, 7(1.3%) others. CIP developed in 23 (4.38 %) patients. There were 15(65%) males, 8 females (35%), 20(86.9%) Caucasians and 2(8.6%) African Americans. Median age was 67 Yrs. (range 29-80). Six out of 23 (26%) patients with CIP developed PCP infection. Median ALC in the patients with PCP infection was 0.75 K/uL (range 0.2-0.83) compared to 1.14 K/uL (range 0.18 - 1.76) in those without PCP infection (p = 0.0182). Conclusions: In patients with CIP, low ALC and prolonged steroid therapy are more likely to result in PCP infection as opposed to steroid therapy alone. Low ALC and prolonged steroid therapy may select patients who require PCP prophylaxis. [Table: see text]

Curious Case of a Year-Long History of Cold Subcutaneous Abscesses

Abstract Cold subcutaneous abscess (CSA) is an abscess lacking classic inflammatory signs. This is a case of a 27-year-old incarcerated African American man who presented with 1-year history of soft, painless, mobile, masses on his limbs. Chest computed tomography scan showed diffuse reticulonodular infiltrates with right lower lobe mass. Computed tomography scan of the right upper extremity showed fluid density with no deep tissue involvement. Coccidioides complement fixation titers are 1:64, IgG 1.315, and IgM 0.242. Lung biopsy and CSA aspiration showed thick walled black spherules with endospores consistent with disseminated coccidioidomycosis (DCM). Cold subcutaneous abscess is a rarely reported manifestation of DCM. Defective cell-mediated immunity and inhibition of inflammation were thought to play a role in DCM and CSA pathogenesis. Cold subcutaneous abscess can remain unnoticed because of lack of inflammation. Our patient has longest time a CSA lasted without other symptoms of DCM. It is important to recognize it early to uncover a potentially dangerous disease.

RAB27A mutation in a patient with griscelli syndrome type 2, successfully cured by hematopoietic stem cell transplantation: Sustained remission

Griscelli syndrome (GS) is a rare autosomal recessive disorder. It features with clinical constellation of skin hypopigmentation, silvery-gray hair, associated with neurological involvement (type I), or defective cell-mediated immunity with hemophagocytosis (type II) that leads to recurrent infection, and patients succumb to death in early childhood or isolated “quiet” GS (type III). To our knowledge, more than sixty patients have been reported mainly from the Mediterranean region with the first reported Saudi cases, reported by Harfi et al. in 1992. The outcome of GS is guarded if not treated early due to recurrent fulminant infections, disease recurrence, and the impending severity of central nervous system disease. Hematopoietic stem cell transplantation (HSCT) is the single current therapeutic treatment for GS II. HSCT, therefore, should be performed as early as possible to prevent potential complications. The reported patient had sustained remission and normal hematopoietic function after allogeneic bone marrow transplant from a human leukocyte antigen-identical sibling donor. GS II syndrome should be considered in any child with hypopigmented skin, silvery-gray hair, and primary immunodeficiency. Early recognition and early HSCT intervention are associated with favorable outcome.

2572. Decreased T-Cell Response, but Appropriate Antibody Production to Tetanus Vaccine Among HIV-Exposed Uninfected Infants in Botswana

BackgroundIn Botswana, more than 10% of HIV-exposed, uninfected infants (HEU) are hospitalized or die in the first 6 months of life, largely due to infectious causes. Vaccine responses can act as a marker of the immune response to infectious antigens. Previous studies of vaccine responses in HEU have had conflicting results. We compared T-cell responses to tetanus and purified protein derivative (PPD), and antibody titers to tetanus, between HEU and HIV-unexposed infants (HUU).MethodsA total of 443 HIV-infected and 451 HIV-uninfected mothers and their 453 HEU/457 HUU live-born infants were followed from pregnancy/delivery through 24 months postpartum in a prospective observational study in Botswana (“Tshipidi”). T-cell expression of interferon (IFN)-γ and interleukin (IL)-2 were measured at 6 months using FluoroSpot after stimulation with tetanus toxoid or PPD. Quantitative tetanus toxoid IgG was measured in plasma at 18 months using ELISA. Mean spot-forming units (sfu) per 105 cells and geometric mean antibody titers were compared between HEU and HUU infants who had received 3 doses of tetanus and 1 dose of Bacille Calmette–Guérin (BCG) vaccines by 6 months, and 3 or 4 doses of tetanus vaccine by 18 months. Results. Peripheral blood mononuclear cells were available at 6 months for 63 HEU and 18 HUU. Plasma was available at 18 months for 39 HEU and 42 HUU. HEU infants had significantly lower IL-2 expression after tetanus stimulation than HUU infants (4.4 vs. 16.1 sfu/105 cells, P = 0.004; figure), but no difference in IFNγ expression. There were no differences in T-cell responses to PPD between HEU and HUU. There were no differences in tetanus geometric mean antibody titers between HEU and HUU. Conclusion. In this cohort of infants from Botswana, we found decreased T-cell responses, but not antibody responses, to tetanus toxoid and no differences in T-cell responses to PPD. Cell-mediated immune defects may play a greater role than humoral immune defects in the increased susceptibility to infection among HEU. BCG vaccine produces robust T-helper 1 responses, which may overcome cell-mediated immune defects in HEU. Disclosures All authors: No reported disclosures.

A rare case of disseminated histoplasmosis masquerading as vulvar cancer in HIV-infected patient: a case report

Background: Histoplasmosis is a systemic mycosis caused by thermally dimorphic fungus Histoplasma capsulatum. It can be found endemically in the United States within the Ohio and Mississippi River Valleys. The symptoms are often self-limiting in the immunocompetent person. In those with cell-mediated immunity defects, histoplasmosis can disseminate causing multi-organ manifestations. Two to twenty-five percent of HIV positive patients living in endemic areas are affected by histoplasmosis. In more than half of these patients, histoplasmosis is the first manifestation of this immunocompromised state. Here, we present a rare manifestation of disseminated histoplasmosis presenting as an indolent non-healing ulcerative lesion masquerading as vulvar cancer.

Enhanced Spontaneous Anti-Tumor Cytotoxicity of Natural Killer Cells in Cutaneous T-Cell Lymphoma Patients

Abstract Cutaneous T-cell lymphoma (CTCL) is characterized by the expansion of malignant CD4+ T cells in the skin. There are two main subtypes of CTCL, mycosis fungoides (MF) and Sezary syndrome (SS). Previous studies have demonstrated defects in cell-mediated immunity, including altered cytokine profiles and decreased neutrophil function, and patients often have recurring bacterial and viral infections. Recent studies have shown increased expression of interleukin (IL)-15 in malignant CD4+ T cells in CTCL patients (Mishra et al., Cancer Discovery, 2016). Since IL-15 can enhance NK cell differentiation and activation, we hypothesized that NK cells from CTCL patients might have phenotypic and functional alterations due to these changes in homeostatic IL-15 levels. To evaluate the absolute number of NK cells in CTCL patients, CD56+Lineage- lymphocytes were quantitated by flow cytometry. SS patients had significantly fewer NK cells as compared to normal donors (mean ± SEM of absolute cell numbers in normal donors=0.2442 ± 0.02, n=51; SS=0.1072 ± 0.02, n=9; MF=0.2161 ± 0.01, n=112; unpaired t-test normal vs. SS, p=0.007). NK cell counts were significantly associated with overall survival, with the short-term risk of death increasing by 87.5% for every increase in 0.1 of absolute NK cell counts on univariate analysis utilizing the Cox proportional hazards model (Figure 1A; p=0.0413). We then examined the cytotoxic capacity of NK cells (CD56+Lineage-) freshly purified from both MF and SS patients by standard chromium release assay. There was a significantly higher level of specific lysis of tumor cells (K562 target cells) by NK cells from CTCL patients as compared to normal donors (Figure 1B, at 50:1 ratio mean ± SEM of percent NK cell cytotoxicity in normal vs CTCL = 27.47 ± 4.76, n=13 vs. 52.54 ± 4.88, n=12, unpaired t-test, p=0.001). Upon further transcript analysis of NK cell cytolytic mediators from CTCL patients compared to normal donors, we observed significantly increased levels of perforin (mean ± SEM of relative RNA in normal vs CTCL = 91.39 ± 9.18, n=3 vs. 485.7 ± 43.15, n=7, unpaired t-test, p=0.0004) and granzyme B (143 ± 23.79, n=3 vs. 431 ± 68.13, n=7 unpaired t-test, p=0.03). In addition, we observed increased levels of interferon-gamma and Fas Ligand (5.149 ± 0.4775, n=3 vs.13.93 ± 1.52, n=7; unpaired t-test p=0.007), indicating NK cells from CTCL patients exhibited consistently elevated activation patterns as compared to normal donor NK cells. We then examined the expression pattern of the IL-15 receptor complex on NK cells in CTCL patients as compared to normal donors by RNA sequencing. There was a significant elevation in IL-15Rα (mean ± SEM of relative RNA in normal vs CTCL = 0.8677 ± 0.1018, n=3 vs. 1.772 ± 0.2055, n=7; p=0.03) and IL-15Rγ (57.02 ± 7.525, n=3 vs. 154.7 ± 12.14, n=7; p=0.001), while IL-15Rβ was also elevated (128 ± 23.68, n=3 vs. 223.2 ± 25.43, n=7; p=0.056). Next we evaluated protein levels of phosphorylated signal transducer and activator of transcription 5 (p-STAT5) in fresh whole blood as the surrogate marker of IL-15 signaling. Preliminary findings demonstrate an increase in p-STAT5 in CTCL patients as compared to normal donors (mean ± SEM of fluorescent intensity in normal donors vs CTCL patients =1506 ± 90.82, n=5 vs. 1270 ± 50.59, n=4; unpaired t-test; p=0.07). These data suggest that NK cell activation is enhanced in patients with CTCL, including MF patients with disease localized to the skin. Further investigations aimed at understanding the disconnect between NK cell numbers, activation, and disease control in CTCL patients are warranted. Download : Download high-res image (197KB) Download : Download full-size image Disclosures Porcu: Kiowa: Research Funding; Miragen: Research Funding; Celgene: Research Funding; Tetralogic: Research Funding; Innate Pharma: Research Funding; Kura: Research Funding; Galderma: Research Funding; Cell Medica: Research Funding. William: Miragen: Consultancy, Honoraria.

Fate of T Cells and their Secretory Proteins During the Progression of Leprosy.

Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Ridley and Jopling classified the disease into five polar forms, Tuberculoid (TT) and Lepromatous (LL), in between two forms of the disease Borderline tuberculoid (BT), Borderline (BB) and Borderline lepromatous (BL) are laid. The tuberculoid type (BT/TT) leprosy patients show good recall of cellmediated immune (CMI) response and Th1 type of immune response, while lepromatous leprosy (LL) patients show defect in cell-mediated immunity to the causative agent and Th2 type of immune response. Due to distinct clinical and immunological spectra of the disease, leprosy attracted immunologists to consider an ideal model for the study of deregulations of various immune reactions. Recent studies show that Tregs, Th3 (TGF-β, IL-10), IL-35 producing Treg immune response associated with the immune suppressive environment, survival of bugs. IL-17 producing Th17 immune response associated with tuberculoid leprosy and play protective role. γδ T cells also increased from tuberculoid to lepromatous pole of leprosy. In this review, we will discuss the role of various subtypes of T-cell and their cytokines in the pathogenesis of leprosy.

High Incidence of Pulmonary Tuberculosis in ART Naive Remunerated Blood Donors with Human Immunodeficiency Virus Type-1 Infection: Possible Role of Iron Overload

Iron overload is reported to be associated with immune alterations and increased susceptibility to infections. HIV infection is characterized by progressive immunodeficiency leading to invasion by opportunistic pathogens. It was of interest to find out if disease course in HIV type-1 infection could have any relation with alteration in body iron status among individuals with history of oral iron intake. A follow-up study of immunologic and virologic markers in relation to disease progression was undertaken on asymptomatic HIV-1 positive blood donors with history of oral iron intake (subgroup I) compared to those without such history (subgroup II). High serum iron was associated with elevated levels of Th2 category of cytokines, heightened immune activation, faster decline in CD4 + T lymphocyte count and higher viral set point. Pulmonary tuberculosis (PT) was the most common AIDS related illness (ARI) (>70%) recorded among subgroup I compared to non-PT category of ARI. Median ARI free duration (months) was shorter among those who developed PT compared to those developing non-PT category of ARI i.e. 30 (95% CI as 26,32) versus 67(95% CI as 60,71) in subgroup I and 47 (95% CI as 42,49) versus 80 (95% CI as 72,87) in subgroup II (P P < 0.001 for PT versus non-PT in both subgroups). The present study indicates that body iron overload resulting from excess intake of iron may be associated with qualitative defects in cell mediated immunity at early stage of HIV-1 infection that may facilitate subsequent acquisition of pulmonary tuberculosis, shorter ARI free duration and reduced survival.

Skin Manifestations in Patients with Adult-onset Immunodeficiency due to Anti-interferon-gamma Autoantibody: A Relationship with Systemic Infections.

Adult-onset immunodeficiency due to anti-interferon-γ autoantibody is an emerging acquired immunodeficiency with frequent skin manifestations. A retrospective chart review was conducted and identified 41 patients with the syndrome. Skin involvement was detected in 33 (80%) patients, 15 (45%) with infective skin diseases and 27 (82%) with reactive skin disorders. Reactive lesions were mostly neutrophilic dermatoses, e.g. Sweet syndrome. Of note, the presence of neutrophilic dermatoses was highly associated with infections of other sites. An adjusted odds ratio for the existence of infections in patients with neutrophilic dermatoses was 14.79 (95% CI: 5.13, 42.70; p < 0.001). Moreover, neutrophilic dermatoses were significantly correlated with opportunistic infections observed in those with defects in cell-mediated immunity including non-tuberculous mycobacterium and disseminated fungal infection. The odds ratio for opportunistic infections in the presence of neutrophilic dermatoses was 12.35 (95% CI: 5.00, 30.55; p <0.001). Thus, the presence of neutrophilic dermatoses in patients with the syndrome can signal opportunistic infections that warrant physician attention.

Features and outcomes of immunoglobulin therapy in patients with Good syndrome at Thailand's largest tertiary referral hospital.

Good syndrome (GS) is an adult-onset immunodeficiency characterized by coexisting thymoma and hypogammaglobulinemia. Clinical course after treatment with intravenous immunoglobulin (IVIg) has rarely been reported. To investigate and report the clinical course and outcomes of GS patients after treatment with IVIg at Thailand's largest national tertiary referral hospital METHODS: This retrospective chart review included patients diagnosed with GS and treated with IVIg during the 1 January 2005 to 31 December 2015 study period. Nine GS patients with a median age at diagnosis of 53 years were included. Pneumonia and sepsis were the most common clinical manifestations. Six infectious organisms suggestive of cell-mediated immunity defect occurred in six patients, including cytomegalovirus (CMV), Mycobacterium tuberculosis, Mycobacterium abscessus, Herpes simplex virus (HSV), Pneumocystis jirovecii, and Aspergillus. Mean serum IgG level was 317 mg/dL. Eight patients had very low to undetectable B-cells. Five patients had either low CD4 number or impaired T-cell function, and one patient had both. All patients received IVIg replacement therapy monthly at a dose of 0.4 g/kg. The mean trough IgG level was 881 mg/dL. After treatment with IVIg replacement, seven patients had favorable clinical outcomes. However, two patients expired due to septicemia. Clinical outcomes of patients with GS are more dependent on the severity of infections and associated hematologic and autoimmune diseases than on the severity of thymoma itself. Therefore, early recognition and prompt IVIg replacement may change the natural course of this condition and may be successful in keeping the patient infections free.

Possible role of interleukin-17 and macrophage migration inhibitory factor in cutaneous warts.

Cutaneous warts (CW), or verrucae, are benign proliferation of skin that result from infection with human papilloma viruses. Cellular immune reactivity plays a significant role in wart regression. The aim of this study was to elucidate the cellular immune status of patients with CW through measurements of their serum levels of interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF,) and, identify the possible role of IL-17 and MIF in CW. We assessed serum IL-17 and MIF levels in patients with different forms of CW and compare the results with controls. Serum levels of IL-17 and MIF were measured using commercially available ELISA assay kits in 60 patients with CW and 20 healthy controls. Serum levels of IL-17 and MIF were significantly lower in patients with CW when compared with the controls (P-value <.01, <.05, respectively). There was nonsignificant correlation between IL-17 and MIF. Low IL-17 and MIF levels may have a contributory role in occurrence, maintenance, severity, and recurrence of different types of CW which depend mainly on the defect of cell-mediated immunity. This may shed new light on nontraditional strategies for the future medical treatments of CW through regulation of IL-17 and MIF.

A Pilot Study of the Prevalence of Anal Human Papillomavirus and Dysplasia in a Cohort of Patients With IBD.

Defective cell-mediated immunity increases the risk of human papillomavirus-associated anal dysplasia and cancer. There is limited information on anal canal disease in patients with IBD. The purpose of this study was to assess anal/vaginal human papillomavirus and anal dysplasia prevalence in patients with IBD. Patients had an anal examination before routine colonoscopy. The study was conducted at a tertiary IBD referral center. We studied a convenience sample of sexually active male and female patients with IBD who were not on biological therapy. Anal examination, anal and vaginal human papillomavirus testing, anal cytology, and high-resolution anoscopy/biopsy were carried out. Anal and vaginal human papillomavirus types, anal cytology, and biopsy grade were measured. Twenty-five male and 21 female evaluable participants, 31 with Crohn's disease, 14 with ulcerative colitis, and 1 with indeterminate colitis, were predominantly white (91.3%), treatment experienced (76.1%), an average age of 38.1 years (range, 22.0-66.0 y), and had an average length of IBD diagnosis of 9.3 years (range, 1.0-33.0 y). Eighteen (39.1%) had an abnormal perianal examination and 3 (6.5%) had an abnormal digital examination. Forty-one (89.1%) had anal human papillomavirus, 16 with a single type and 25 with multiple types (range, 2-5 types). Human papillomavirus type 16 was most common (65.2%), followed by human papillomavirus types 11 and 45 (37.0% each). Nineteen of 21 (90.5%) women had vaginal human papillomavirus. Overall, 21 (45.7%) had abnormal anal cytology. Thirty three (71.7%) had ≥1 anal biopsy (9 had multiple), with dysplasia diagnosed in 28 (60.9%) and high-grade and low-grade squamous intraepithelial lesions diagnosed in 4 (8.7%) and 24 (43.5%). No control group was included, and no detailed sexual history was taken. A high prevalence of anal and vaginal human papillomavirus and anal dysplasia was demonstrated in the study population outcomes. See Video Abstract at http://links.lww.com/DCR/A379.

Disseminated Nocardiosis in a Patient with Lepromatous Leprosy

Disseminated nocardiosis is a serious opportunistic infection with very high mortality, especially in individuals with defective cell mediated immunity. The use of immunosuppressant therapy is associated with increased risk of opportunistic infections and in south-east Asian countries where tuberculosis is widely prevalent, Nocardia is an often overlooked and under diagnosed pathogen, with clinically very similar presentations. Here we report a case of disseminated nocardiosis presenting as multifocal brain, in a patient with Lepromatous Leprosy, who was on immunosuppressive therapy for Type 2 Lepra reactions. An early diagnosis requires high index of suspicion and interventions like stereotactic brain surgery and is a determinant for positive clinical outcome.

Recurrent Vulvovaginal Candidiasis: Could It Be Related to Cell-Mediated Immunity Defect in Response to Candida Antigen?

Recurrent vulvovaginal candidiasis (RVVC) is a common cause of morbidity affecting millions of women worldwide. Patients with RVVC are thought to have an underlying immunologic defect. This study has been established to evaluate cell-mediated immunity defect in response to candida antigen in RVVC cases. Our cross-sectional study was performed in 3 groups of RVVC patients (cases), healthy individuals (control I) and known cases of chronic mucocutaneous candidiasis (CMC) (control II). Patients who met the inclusion criteria of RVVC were selected consecutively and were allocated in the case group. Peripheral blood mononuclear cells were isolated and labeled with CFSE and proliferation rate was measured in exposure to candida antigen via flow cytometry. T lymphocyte proliferation in response to candida was significantly lower in RVVC cases (n=24) and CMC patients (n=7) compared to healthy individuals (n=20, <0.001), but no statistically significant difference was seen between cases and control II group (P>0.05). Family history of primary immunodeficiency diseases (PID) differed significantly among groups (P=0.01), RVVC patients has family history of PID more than control I (29.2 vs. 0%, P=0.008) but not statistically different from CMC patients (29.2 vs. 42.9%, P>0.05). Prevalence of atopy was greater in RVVC cases compared to healthy individuals (41.3 vs. 15%, P=0.054). Lymphoproliferative activity and vaginal symptoms were significantly different among RVVC cases with and without allergy (P=0.01, P=0.02). Our findings revealed that T cells do not actively proliferate in response to Candida antigen in some RVVC cases. So it is concluded that patients with cell-mediated immunity defect are more susceptible to recurrent fungal infections of vulva and vagina. Nonetheless, some other cases of RVVC showed normal function of T cells. Further evaluations showed that these patients suffer from atopy. It is hypothesized that higher frequency of VVC in patients with history of atopy might be due to allergic response in mucocutaneous membranes rather than a functional impairment in immune system components.

Cytokines as biomarkers to monitoring the impact of multidrug therapy in immune response of leprosy patients

Leprosy or Hansen’s disease is a chronic infectious disease of the skin and nerves, caused by the intracellular bacilli Mycobacterium leprae. It is characterized by a spectrum of clinical forms depending on the host’s immune response to M. leprae. Patients with tuberculoid (TT) leprosy have strong cell-mediated immunity (CMI) with elimination of the bacilli, whereas patients with lepromatous (LL) leprosy exhibit defective CMI to M. leprae. Despite advances in the understanding of the pathogenesis of leprosy and the development of new therapeutic strategies, there is a need for the identification of biomarkers which be used for early diagnosis and to discrimination between different forms of the disease, as prognostic markers. Here, we analyzed the serum levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-γ and TNF in order to address the contribution of these cytokines in late phase of M. leprae infection, and the impact of multidrug therapy (MDT). Our results demonstrated that patients of LL group presented higher expression of serum levels of inflammatory cytokines before MDT, while TT patients presented a balance between inflammatory and regulatory cytokines. MDT changes the profile of serum cytokines in M. leprae infected patients, as evidenced by the cytokine network, especially in TT patients. LL patients displayed a multifaceted cytokine system characterized by strong connecting axes involving inflammatory/regulatory molecules, while TT patients showed low involvement of regulatory cytokines in network overall. Cytokines can be identified as good biomarkers of the impact of MDT on the immune system and the effectiveness of treatment.

Epidermodysplasia Verruciformis-A Genetic Disorder

verruciformis also known as Tree man disease. It is recognized as an inherited disorder with wide spread and persistent with human papilloma virus causes defect in cell mediated immunity. It is a rare, lifelong, cutaneous, autosomal recessive genetic disorder of the immune system manifested by (HPV) infection beginning in the early years of life. This disorder was first described by Lewandowsky and Lutz 1 in 1922 as an epidermal nevus. In 1939, Sullivan and Ellis2 described a close relationship between EV and high risk of skin cancer. In EV, there are mutations in the EVER1 or EVER2 genes on chromosome 17q25, which, due to a defect of cell-mediated immunity, lead to an abnormal susceptibility of the patients to a specific group of HPV genotypes known as EV HPV. Most of these are HPV 5 and 8; more rarely, HPV 14,17, 20 and 47, and all have oncogenic po-tential3 In the addition, there is a link with squamous cell carcinoma. A tree man syndrome is a rare disorder happening more frequently at a younger age in the general population. It is an unusual Geno dermatosis character-ized by an autosomal recessive inheritance pattern. Non-surgical therapies and surgical therapies are known to treat this disorder, but it is known to be lifelong disorder. Recent surgery was performed in Bangladesh which is known to be successful How to Cite this Article Pubmed Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. Verruciformis-A Genetic Disorder. SRP. 2017; 8(1): 71-75. doi:10.5530/srp.2017.1.12 Web Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. Verruciformis-A Genetic Disorder. http://www.sysrevpharm.org/?mno=302644566 [Access: March 28, 2021]. doi:10.5530/srp.2017.1.12 AMA (American Medical Association) Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. Verruciformis-A Genetic Disorder. SRP. 2017; 8(1): 71-75. doi:10.5530/srp.2017.1.12 Vancouver/ICMJE Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. Verruciformis-A Genetic Disorder. SRP. (2017), [cited March 28, 2021]; 8(1): 71-75. doi:10.5530/srp.2017.1.12 Harvard Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha (2017) Verruciformis-A Genetic Disorder. SRP, 8 (1), 71-75. doi:10.5530/srp.2017.1.12 Turabian Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. 2017. Verruciformis-A Genetic Reviews in Pharmacy, 8 (1), 71-75. doi:10.5530/srp.2017.1.12 Chicago Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. Epidermodysplasia Verruciformis-A Genetic Disorder. Systematic Reviews in Pharmacy 8 (2017), 71-75. doi:10.5530/srp.2017.1.12 MLA (The Modern Language Association) Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha. Epidermodysplasia Verruciformis-A Genetic Disorder. Systematic Reviews in Pharmacy 8.1 (2017), 71-75. Print. doi:10.5530/srp.2017.1.12 APA (American Psychological Association) Style S. Swati, K. Sowjanya, R. Lakuma, S. A. Sunaina, G. Srividya, V. Rohitha (2017) Verruciformis-A Genetic Reviews in Pharmacy, 8 (1), 71-75. doi:10.5530/srp.2017.1.12

No Difference in Antibody Responses to Tetanus Vaccine Among HIV-Exposed and -Unexposed Infants in Botswana

BackgroundIn Botswana, more than 10% of HIV-exposed, uninfected infants (HEU) are hospitalized or die in the first 6 months of life, largely due to infectious causes. Vaccine responses can act as a marker of the immune response to infectious antigens. Previous studies of antibody responses to vaccines in HEU have had conflicting results. We compared antibody titers to tetanus vaccine between HEU and HIV-unexposed infants (HUU), and explored whether tetanus antibody titers predicted risk of hospitalization in the first 2 years of life among HEU.Methods443 HIV-infected and 451 HIV-uninfected mothers and their 453 HEU / 457 HUU live-born infants were followed in a prospective observational study in Botswana (“Tshipidi”). Quantitative tetanus toxoid IgG was measured in plasma samples from 18-month-old infants. Geometric mean antibody titers (GMT) were compared between HEU and HUU infants, and between HEU infants who were or were not hospitalized by age 2.ResultsPlasma was available at 18 months for 39 HEU and 42 HUU infants. Within this subset, there were 15 hospitalizations (12 in HEU) [RR of hospitalization among HEU = 1.34 (P = 0.009)]. 73% of hospitalizations overall, and 83% in HEU, were due to infection (primarily pneumonia/bronchiolitis and gastroenteritis). Among infants who had received 3 or 4 doses of tetanus vaccine by 18 months, there were no significant differences in tetanus GMT between HEU and HUU (Fig A). Among HEU who had received 3 or 4 doses of tetanus vaccine by 18 months, there were no significant differences in tetanus GMT between infants who were hospitalized and infants who were not (Fig B).ConclusionIn this small sample of infants from Botswana, we did not identify differences in antibody responses to tetanus vaccine between HEU and HUU. Although HEU demonstrated an increased risk of hospitalization, response to tetanus vaccine did not appear to be a significant predictor of morbidity. It is possible that cell-mediated immune defects play a larger role than humoral immune defects in the increased susceptibility to infection among HEU.Disclosures All authors: No reported disclosures.