Immunosuppressive Disease Research Articles

Transcriptome analysis of chicken intraepithelial lymphocyte natural killer cells infected with very virulent infectious bursal disease virus

The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.

Genome-wide analysis of differentially expressed mRNAs, lncRNAs, and circRNAs in chicken bursae of Fabricius during infection with very virulent infectious bursal disease virus

BackgroundInfectious bursal disease virus (IBDV) causes acute, highly contagious, immunosuppressive, and lethal infectious disease in young chickens and mainly infects the bursa of Fabricius (BF). To investigate interactions between IBDV and its host, RNA sequencing was applied to analyze the responses of the differentially expressed transcriptional profiles of BF infected by very virulent IBDV (vvIBDV).ResultsIn total, 317 upregulated and 94 downregulated mRNAs were found to be significantly differentially expressed in infected chickens, compared to controls. Long non-coding RNA (lncRNA) and circular RNA (circRNA) alterations were identified in IBDV-infected chickens, and significantly different expression was observed in 272 lncRNAs and 143 circRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the functions of significantly dysregulated genes, which showed that the JAK-STAT signaling pathway, the NOD-like receptor signaling pathway, and apoptosis may be activated by IBDV infection. We predicted interactions between differentially expressed genes and produced lncRNA-mRNA and circRNA-miRNA-mRNA regulator network.ConclusionsThe present study identified the expression profiles of mRNAs, lncRNAs, and circRNAs during vvIBDV infection and provides new insights into the pathogenesis of IBDV and antiviral immunity of the host.

An optimized secretory expression system and immunogenicity evaluation for glycosylated gp90 of avian reticuloendotheliosis virus

Reticuloendotheliosis is an important immunosuppressive disease, associated with avian reticuloendotheliosis virus (REV) infection, and causes notable economic losses worldwide. Glycoprotein gp90 is an important structural protein of REV, and considered to be the most important immunogenic antigen, which can induce neutralizing antibodies against REV. In this study, an optimized suspension culture system was developed and applied to secretory express the immunogenic surface antigen gp90. To achieve an optimal glycosylation, the gp90 was designed to secretory expressed into the supernatant of the cell culture, which also occurs in the natural protein maturation procedure of REV. Serum-free culture medium was introduced to simplify the purification process and reduce the production costs. Based on the purified glycosylated gp90, an oil-emulsion subunit REV vaccine candidate was developed and evaluated in chickens. The subunit gp90-based vaccine induced fast immune responses, high levels of antibodies (REV-specific antibody, gp90-specific antibody, and neutralizing antibody against REV), and preferential T helper 2 (Th2) (interleukin-4 secretion) not Th1 (interferon-γ secretion) response. Furthermore, the viremia induced by REV infection was significantly reduced in chickens immunized with the glycosylated gp90. Overall, an optimized secretory expression system for glycosylated gp90 was developed, and the glycosylated gp90 obtained in this study retained good immunogenicity and could be an attractive vaccine candidate to protect chickens against REV horizonal infection.

New Insights Into Systemic Lupus Erythematosus Therapies: 2010-2020.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that may affect every organ. The multiple pathogenic mechanisms and heterogeneous phenotypes of SLE present unique challenges in the management of this complex disease. This article discusses new SLE therapies from the last 10 years. We will address new information in the realms of lifestyle interventions, antimalarials, nonsteroidal anti-inflammatory drugs, glucocorticoids, immunosuppressive disease modifying antirheumatic drugs, biological therapies, and other modalities as they pertain to SLE.

Asthma and COPD Are Not Risk Factors for ICU Stay and Death in Case of SARS-CoV2 Infection

BackgroundAsthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease.ObjectiveTo evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19).MethodsWe collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic.ResultsAmong patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death.ConclusionAsthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection.

S2278 What Happens When SARS-COV2 Infection Overlaps With Administration of Anti-TNF Therapy in an IBD Patient?

INTRODUCTION: COVID-19 is now a global pandemic and immunosuppression is widely suspected to be a risk factor for more severe outcomes. We present a worst-case scenario of COVID-19 establishing itself at the time of maintenance administration of anti-TNF therapy in a patient. CASE DESCRIPTION/METHODS: The patient is a 60-year-old female with a history of Rheumatoid Arthritis, Systemic Lupus Erythematosus, and ileocolonic inflammatory Crohn’s disease in remission on weekly adalimumab and methotrexate. She presented to the emergency department (ED) with one day of fevers and generalized myalgias and was discharged home with a diagnosis of influenza-like illness. She was asked to quarantine pending COVID-19 test results, which returned positive three days later. Her last dose of adalimumab was administered 5 days prior and methotrexate 7 days prior. The next day she developed gastrointestinal symptoms including diarrhea, nausea, emesis, and abdominal cramping, not consistent with her usual Crohn’s flares. She also noted new onset shortness of breath and returned to the ED. Vitals were Tmax 101.1F, BP 152/80, HR 109, RR 17, O2 Sat 99% on room air. CT scan of chest and abdomen revealed patchy lung consolidations, and colitis in the proximal sigmoid colon. Clostridium difficile stool test was negative, fecal calprotectin was normal at 19. She was treated with our COVID-19 hospitalization protocol, which consisted of hydroxychloroquine, azithromycin, and ascorbic acid. Supplemental oxygen was required for two days. She defervesced after day 4 of hospitalization and was discharged after day 5. DISCUSSION: This case provides some of the details in regard to timing of infection and administration of immunosuppressive therapy. Theoretically, immunosuppressed inflammatory bowel disease (IBD) patients are at the highest risk for morbidity and mortality from COVID-19. SARS-CoV-2 has an average incubation period of five days, we estimate our patient administered adalimumab and methotrexate during the pre-symptomatic post infection period (Figure 2). Although we expected her condition would deteriorate, within two days she improved with interventions recently shown to have no benefit in the treatment of COVID-19. We hypothesize that the adalimumab may have interfered with COVID-19’s aberrant immune response, leading to a less severe disease course. We are hopeful this case and additional outcomes studies will help clarify concerns about immunosuppressed populations during the pandemic.Table 1.: Laboratory TrendFigure 1.: CT ABDOMEN AND PELVIS.Figure 2.: TIMELINE.

Novel variant infectious bursal disease virus suppresses Newcastle disease vaccination in broiler and layer chickens

Newcastle disease (ND) is one of the most important avian diseases that seriously threaten the poultry industry worldwide. Sometimes vaccination might not effectively reduce ND occurrence in some poultry farms for unclear reasons. Infectious bursal disease (IBD) is one of the most important immunosuppressive diseases, and the novel variant IBD virus (IBDV) is threatening chicken farms in China. This study evaluated the influence of the novel variant IBDV (SHG19 strain) on immunization of ND vaccine (LaSota strain) in broiler and layer chickens. In commercial broilers, the hemagglutination inhibition antibody titers against LaSota strain were decreased by the prior infection of the novel variant IBDV. Pathological examination revealed that the novel variant IBDV severely damaged the key immune organs of the bursa and spleen, and the B lymphocytes in the bursa were severely destroyed, which was the primary reason involved in the immunosuppression on ND vaccination. Moreover, the novel variant IBDV dramatically reduced the BW of infected broilers by about 16% compared to that of control, which indicated huge economic losses. Furthermore, this study confirmed the immunosuppression induced by the novel variant IBDV in specific pathogen–free layer chickens. In this study, it was discovered that the novel variant IBDV could interfere with ND vaccination in both broilers and layers, which was one important factor involved in immune failure in poultry farms. This study therefore suggests the urgency to control the novel variant IBDV infection for healthy breeding.

小児におけるCOVID–19の特徴と救急診療上の注意点(Characteristics and considerations in the medical treatment for COVID–19 in children)

要旨 小児における新型コロナウイルス（SARS–CoV–2）による感染症（COVID–19）は，軽症患者が圧倒的に多く，重症化する割合や，死亡の割合は非常に小さい。重症化した小児では，喘息を含む慢性肺疾患，心血管系疾患，免疫抑制状態の患者が多く，基礎疾患をもつ小児では特に注意を要すると考えられている。最近，小児COVID–19の確定または疑い患者において，肺炎像がないにもかかわらず，長引く発熱，腹痛，心機能低下などを伴い，強い炎症反応を呈する症例が報告されているが，SARS–CoV–2感染との関連はまだ不明な点が多い。小児の特徴として不顕性感染が多く，家族内や地域，医療機関において感染源となることが懸念されている。救急医療の現場では不顕性感染の可能性を考慮した感染予防策が必要である。一方，感染予防対策としての外出制限や休校措置は，健康な小児に対し，予想を超える精神的・身体的な影響を及ぼしている可能性がある。身体症状を訴えて受診するなかに精神的なサポートを必要とする小児や，社会的に孤立し救急外来への受診が唯一の社会的接点になっている小児がいる可能性を考慮して，必要に応じソーシャルワーカーなど多職種と連携して対応することが重要である。

VACCINE-PREVENTABLE INFECTIONS AMONG SOLID ORGAN TRANSPLANT RECIPIENTS: A DATA-LINKED COHORT STUDY, AUSTRALIA, 2000-2015

Introduction: Infections are a common cause of morbidity and mortality among solid organ transplant recipients. Some infections are preventable with vaccination. Rates of these infections vary with immunosuppression, vaccination rates and baseline disease prevalence. Both adherence with and response to vaccination in this population are variable, and optimum vaccination strategies continue to be refined. We aimed to characterise the incidence and complications of vaccine-preventable infections in an Australian cohort of transplant recipients compared with the general population. Methods: Eligible participants received a solid organ transplant in New South Wales, Australia, in 2000-2015. Linkage was undertaken between transplant registries and the notifiable conditions information management system. Vaccine-preventable infections were laboratory confirmed diphtheria, Haemophilus influenzae type b, influenza, invasive pneumococcal disease, measles, mumps, pertussis, poliovirus, rubella and tetanus. Extracted information included infection type, date, clinical site, hospitalizations and deaths due to infection. Crude incidence rates were calculated for each infection from transplant date censored at first infection episode, death, loss to follow up or end of observation period (Dec 2016). Standardized incidence ratios (SIR) were calculated relative to Australian population notification rates, standardizing for gender, age (5-year categories) and calendar year. Results: Among 3,394 eligible recipients, 399 vaccine-preventable infections affected 339 (10%) recipients. Influenza was the most common vaccine-preventable infection with 352 notifications among 305 recipients. Influenza cases were much more common among transplant recipients than the general population (SIR 8.9, 95% CI 8.0-10.0, Table 1). In 36 cases (10%), hospitalization was required, and 2 deaths due to influenza were reported.There were 20 notifications of invasive pneumococcal disease (IPD) for 18 recipients. IPD occurred 10.2 times more often among transplant recipients than the general population (95%CI: 6.4-16.2). Most (n=13, 65%) cases were hospitalized, and one patient died from invasive pneumococcal disease. The excess burden of both influenza and IPD decreased over time (Figure 1).Cases of pertussis occurred only slightly more often than in the general population (SIR 1.5, 95%CI: 1.0-2.3). Of 26 cases, there was one reported hospitalization and no deaths due to pertussis. Only one case of mumps, and no other vaccine-preventable infections, were reported. Conclusion: Influenza and IPD occur more frequently among organ transplant recipients than the general population, with appreciable morbidity and mortality. Excess rates of influenza and IPD have decreased over time, which may reflect improvements in vaccination. Other vaccine-preventable infections were not associated with excess disease among transplant recipients. The need for appropriate recipient vaccination is emphasized. NSW Ministry of Health. NHMRC Postgraduate Scholarship GNT1168202.

Clinical outcome of SARS-CoV-2 infection in immunosuppressed children in Spain.

Limited information is available regarding SARS-CoV-2 infections in children with underlying diseases. A retrospective study of children less than 15 years old with primary or secondary immunosuppression infected with SARS-CoV-2 during March 2020 was performed. In this series, 8 immunocompromised patients with COVID-19 disease are reported, accounting for 15% of the positive cases detected in children in a reference hospital. The severity of the symptoms was mild-moderate in the majority with a predominance of febrile syndrome, with mild radiological involvement and in some cases with mild respiratory distress that required oxygen therapy. The rational and prudent management of these patients is discussed, evaluating possible treatments and options for hospitalization or outpatient follow-up.Conclusion: In our experience, monitoring of children with immunosuppression and COVID-19 disease can be performed as outpatients if close monitoring is possible. Hospitalization should be assessed when high fever, radiological involvement, and/or respiratory distress are present.What is Known:• SARS-CoV-2 infection is usually mild in children.What is New:• Outcome of immunosuppressed children with COVID-19 is generally good, with a mild-moderate course.

Metabolic Stress in the Transition Period of Dairy Cows: Focusing on the Prepartum Period.

Simple SummaryComplex pathways of metabolic adaptation occur in high-yielding dairy cows around calving. These adaptations require the redirection of nutrients to support the last stages of fetal growth and the commencement of lactation. Failure to adapt to these changes may result in the development of clinical disease in the postpartum period. Therefore, most existing literature is focused on studying the metabolic changes in the postpartum period. However, some of the risk factors associated with postpartum clinical disease can already be found in the prepartum period. This review describes adaptive changes occurring in prepartum high-yielding dairy cows, from drying off (40 to 60 days before parturition) until calving.All modern, high-yielding dairy cows experience a certain degree of reduced insulin sensitivity, negative energy balance, and systemic inflammation during the transition period. Maladaptation to these changes may result in excessive fat mobilization, dysregulation of inflammation, immunosuppression, and, ultimately, metabolic or infectious disease in the postpartum period. Up to half of the clinical diseases in the lifespan of high-yielding dairy cows occur within 3 weeks of calving. Thus, the vast majority of prospective studies on transition dairy cows are focused on the postpartum period. However, predisposition to clinical disease and key (patho)physiological events such as a spontaneous reduction in feed intake, insulin resistance, fat mobilization, and systemic inflammation already occur in the prepartum period. This review focuses on metabolic, adaptive events occurring from drying off until calving in high-yielding cows and discusses determinants that may trigger (mal)adaptation to these events in the late prepartum period.

Abstract 343: Identifying a novel and aggressive CD52+ve type of prostate cancer: Phenotype distinguishing biomarker and therapeutic target

Abstract Metastatic prostate cancer (PCa) and the development of CRPC are the major causes of mortality in PCa patients. The poor prognosis and failure of therapies in metastatic PCa could be associated to the heterogeneous nature of tumor cells. We previously showed that S100A4 protein drives the metastasis of PCa in preclinical models. On the basis of recent genomic data of >1000 patients, we now provide evidence that S100A4 in association with CD52 forms a unique and aggressive class of PCa in patients. The tumor genome data of patients show a direct correlation between S100A4 and CD52, a small glycoprotein expressed on T, B, NK, dendritic cells and monocytes. We posit that aggressive type of PCa cells during progression acquire immunosuppressive properties. Here, by employing a progressive panel of human PCa cell lines and primary prostate tumors and metastatic tumors, we show the presence of a subpopulation of PCa cells that express high levels of CD52 and S100A4. We were successful in isolating CD52+/S100A4+ subpopulation of aggressive PCa cells from DU145 (brain metastasis model) and PC3 (bone metastasis model). On analysis the CD52+/S100A4+ metastatic cells exhibited higher degree of invasiveness than the parental cells. These cells are characterized by the high expression of S100A4, VEGF and MMP9, phosphorylated-NFκB-p65 and phosphorylated-ERK. By using IHC, we observed that metastatic tumors (brain, bone, testis) exhibiting high S100A4 levels also exhibited high expression of CD52. A marked increase in the number of CD52+/S100A4+ metastatic PCa cells were found in brain in patient Met specimens, that well explains the increased number of such tumor cell types found in DU145 model (isolated from brain). We provide data showing that genetic suppression CD52 (by using siRNA) significantly reduces the growth, migration and invasive potential of metastatic cells. However, suppressing CD52 has no bearing on S100A4 expression. On the contrary, modulation of S100A4 expression could bring changes in the expression of CD52 in PCa cells. These data suggest a potential link between the S100A4 and immunosuppressive type PCa cells human disease. In conclusion, the novelty of this study is that we for the first time identified a new PCa subtype that is aggressive and resistant to existing therapies. Another novel finding is that we identified CD52 as a novel target for treating metastatic PCa. These findings warrant future clinical studies in investigating CD52+/S100A4+ signature as a biopsy biomarker to identify patients (at diagnosis) who are prone to develop metastasis (particularly bone metastasis). In addition our data opens the opportunity to develop new therapies targeting CD52/S100A4 for treating aggressive metastatic PCa which otherwise remains a non-treatable disease. Grant Support: R01CA193739 Citation Format: Adrian Pablo Mansini, Marina G. Ferrari, Arsheed Ganaie. Identifying a novel and aggressive CD52+ve type of prostate cancer: Phenotype distinguishing biomarker and therapeutic target [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 343.

Transmission Dynamics in Tuberculosis Patients With Human Immunodeficiency Virus: A Systematic Review and Meta-analysis of 32 Observational Studies.

There are large knowledge gaps on the transmission dynamics of Mycobacterium tuberculosis in settings where both tuberculosis and human immunodeficiency virus (HIV) are endemic. We aimed to assess the infectiousness of tuberculosis patients coinfected with HIV. We systematically searched for studies of contacts of both HIV-positive and HIV-negative tuberculosis index cases. Our primary outcome was Mycobacterium tuberculosis infection in contacts. Data on sputum smear and lung cavitation status of index cases were extracted from each study to assess effect modification. Secondary outcomes included prevalent tuberculosis and HIV in contacts of HIV-positive and HIV-negative index cases. Of 5255 original citations identified, 32 studies met inclusion criteria, including 25 studies investigating M. tuberculosis infection (Nparticipants = 36 893), 13 on tuberculosis (Nparticipants = 18 853), and 12 on HIV positivity (Nparticipants = 18 424). Risk of M. tuberculosis infection was lower in contacts of HIV-positive index cases (odds ratio [OR], 0.67, 95% confidence interval [CI], .58-.77) but was heterogeneous (I2 = 75.1%). Two factors modified this relationship: the lung cavitary status of the index case and immunosuppression (measured through CD4 counts or HIV or acquired immunodeficiency syndrome diagnoses) among index people living with HIV. Rates of HIV were consistently higher in contacts of coinfected index cases (OR, 4.9; 95% CI, 3.0-8.0). This was modified by whether the study was in sub-Saharan Africa (OR, 2.8; 95% CI, 1.6-4.9) or in another global region (OR, 9.8; 95% CI, 5.9-16.3). Tuberculosis patients coinfected with HIV are less infectious than HIV-uninfected cases when they have severe immunosuppression or paucibacillary disease. Contacts of coinfected index cases are almost 5 times more likely to also have HIV.

Ex vivo rescue of recombinant very virulent IBDV using a RNA polymerase II driven system and primary chicken bursal cells

Infectious Bursal Disease Virus (IBDV), a member of the Birnaviridae family, causes an immunosuppressive disease in young chickens. Although several reverse genetics systems are available for IBDV, the isolation of most field-derived strains, such as very virulent IBDV (vvIBDV) and their subsequent rescue, has remained challenging due to the lack of replication of those viruses in vitro. Such rescue required either the inoculation of animals, embryonated eggs, or the introduction of mutations in the capsid protein (VP2) hypervariable region (HVR) to adapt the virus to cell culture, the latter option concomitantly altering its virulence in vivo. We describe an improved ex vivo IBDV rescue system based on the transfection of an avian cell line with RNA polymerase II-based expression vectors, combined with replication on primary chicken bursal cells, the main cell type targeted in vivo of IBDV. We validated this system by rescuing to high titers two recombinant IBDV strains: a cell-culture adapted attenuated strain and a vvIBDV. Sequencing of VP2 HVR confirmed the absence of unwanted mutations that may alter the biological properties of the recombinant viruses. Therefore, this approach is efficient, economical, time-saving, reduces animal suffering and can be used to rescue other non-cell culture adapted IBDV strains.

Baseline use of angiotensin-converting enzyme inhibitor/AT1 blocker and outcomes in hospitalized coronavirus disease 2019 African-American patients.

The primary objective of this study is to determine the effect of baseline use of angiotensin-converting enzyme inhibitor (ACE-i)/AT1 blocker (ARB) on mortality in hospitalized coronavirus disease 2019 (Covid-19) African-American patients. The secondary objectives are, to determine the effect of baseline use of ACE-i/ARB on the need for mechanical ventilation, new dialysis, ICU care, and on composite of above-mentioned outcomes in the same cohort. In this retrospective study, we analyzed data using electronic medical records from all hospitalized Covid-19 African-American patients, who either died in the hospital or survived to discharge between 2 March and 22 May 2020. Patients were divided into two groups, those on ACE-i/ARB at baseline and those not on them. We used Pearson chi-square test for categorical variables, and Student's t test for continuous variables. We performed multiple logistic regression to test the primary and secondary objectives using SAS 9.4. Out of 531 patients included in the analysis, 207 (39%) were on ACE-i/ARB at baseline. Patients in ACE-i/ARB group were older (64 vs. 57 years, P < 0.001), and had higher prevalence of hypertension (96.6 vs. 69.4%, P < 0.001) and diabetes mellitus (55.6 vs. 34.9%, P < 0.001). There was no difference in sex, BMI, other comorbidities, and presenting illness severity among the groups. After adjustment of multiple covariates, there was no difference in outcomes between the two groups including mortality, need for mechanical ventilation, new dialysis, ICU care, as well as composite outcomes. Baseline use of ACE-i/ARB does not worsen outcomes in hospitalized Covid-19 African-American patients.

Malakoplakia of the gastrointestinal tract: clinicopathologic analysis of 23 cases

BackgroundMalakoplakia is an uncommon, tumor-like inflammatory disease characterized by impaired histiocytes that are unable to completely digest phagocytized bacteria. The genitourinary tract is the most common site of involvement, however, cases have also been described in the gastrointestinal tract, suggesting that it is the second most common site of involvement. This study investigates the clinical and histologic features of malakoplakia in the gastrointestinal tract.Case presentationFor 23 gastrointestinal specimens (biopsies and resections) from patients with a pathologic diagnosis of malakoplakia, we recorded the gender, age, location, primary diagnosis, endoscopic or surgical indication, endoscopic/gross impression and immune status (immunocompromised vs. immunocompetent).ConclusionMalakoplakia occurred throughout the length of the gastrointestinal tract with most of the cases located in the sigmoid colon and rectum (n = 10); other sites included the transverse and descending colon (n = 4), stomach/gastroesophageal junction (n = 4), appendix (n = 2), cecum (n = 1), small bowel (n = 1), and the peri-anal area (n = 1). Endoscopically, these lesions most commonly appeared as polyps (n = 10) or masses (n = 5), other clinical endoscopic impressions varied from a thickened area/fibrosis to mucosal erythema. Most patients were immunocompromised due to a disease state (e.g. organ transplantation, cancer diagnosis, autoimmune condition) and/or medication effect. Eight patients with malakoplakia were on immunosuppressive medications (8/23, 35%). Common immunosuppressed disease states included cancer (n = 9), autoimmune disease (n = 5), status post organ transplantation (n = 4), diabetes (n = 5), infection/sepsis (n = 3), and HIV/AIDS (n = 1). Some patients had multiple co-morbidities (i.e. diabetes and organ transplant). Twenty-one patients with malakoplakia were in an immunosuppressive state (21/23, 91%).

TOXOPLASMOSIS AND CONGENITAL DISTURBANCE

Toxoplasmosis is a disease caused by intracellular protozoan parasites called Toxoplasma gondii. The animal and human could suffer from infections through different routes involving diets, non-hygienic habit, contacts to soil, as well as blood transfusions and organs grafting. Some people with immune-compromised status are at a high risk of infection; examples of these groups are pregnant women, fetuses, and newborns. This study aimed to evaluate the role of Toxoplasma infection in the manifestation of abortions and other congenital disturbances among married women aged 18 to 45 years in Maysan city (in the south of Iraq). Inclusion criteria include the study group with a history of infection with Toxoplasma gondii (100 females) and for controls, those who were free from toxoplasmosis (100 females). Exclusion criteria were pregnant women, unmarried women, and those suffering from immunosuppressive diseases. The serum samples were tested for IgG and IgM against Toxoplasma gondii antigens by using the Biomerieux Mini VIDAS automated immunoassay system, which depended on the principle of Enzyme-Linked Fluorescent Assay (ELFA) technology. The study revealed that infected non-aborted women were 14 (14%), while non-infected non-aborted women were 24 (24%). Infected women with one case of abortion were sixty (60.0%), while non-infected women with one case of abortion were 40 (40.0%). The infected women who had two abortion cases and those infected ones who had more than two cases of abortions were 26 (26%) and 14 (14%), respectively. There was a statistically significant difference between infected and uninfected women regarding abortion (p 0.01). It has been found that there were highly significant differences between infected and non-infected women concerning anomalies and deliveries by cesarean sections (p-value = 0.001). There was a statically significant difference (p-value =0.01) between infected and non-infected women concerning their deliveries with or without premature babies.

The Impact of Immunosuppression on Chronic Kidney Disease in People Living With Human Immunodeficiency Virus: The D:A:D Study.

Relations between different measures of human immunodeficiency virus-related immunosuppression and chronic kidney disease (CKD) remain unknown. Immunosuppression measures included baseline, current, time-lagged and nadir CD4, years and percentage of follow-up (%FU) with CD4 ≤200 cells/μL, and CD4 recovery. CKD was defined as confirmed estimated glomerular filtration rate <60 mL/minute/1.73 m2. Of 33 791 persons, 2226 developed CKD. Univariably, all immunosuppression measures predicted CKD. Multivariably, the strongest predictor was %FU CD4 ≤200 cells/μL (0 vs >25%; incidence rate ratio [IRR], 0.77 [95% confidence interval [CI], .68-.88]), with highest effect in those at low D:A:D CKD risk (IRR, 0.45 [95% CI, .24-.80]) vs 0.80 [95% CI, .70-.93]). Longer immunosuppression duration most strongly predicts CKD and affects persons at low CKD risk more.

Listeria monocytogenes infections: Analysis of 41 patients

ObjectiveWe describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections. MethodsWe performed a retrospective study using positive isolation of Listeria monocytogenes from blood, cerebrospinal fluid, and other organic fluids. Electronic health records were used to determine the epidemiological and clinical features of infections caused by L. monocytogenes. Mortality and sepsis were considered dependent variables in the statistical analyses. ResultsWe included 41 patients in an observation period of 15 years (2003–2018), with an annual incidence rate of 1.3 cases per 100,000 population. Three main population profiles were identified: newborns, pregnant women, and other adults (17.1%, 12.2%, and 82.9%, respectively). Neuroinvasive infection was present in 17 patients (41.5%). In both univariate and multivariate analyses, neurological infections, whether meningoencephalitis, rhombencephalitis, or brain abscesses, were the main risk factors for severe forms of Listeria-related infections (odds ratio 1.8, 95% CI 1.52–2.14, p=0.01). Malignancies, whether solid tumors or hematological neoplasms, immunosuppression, and chronic diseases were not related to either mortality or severe clinical syndromes. ConclusionInfections caused by L. monocytogenes were uncommon but could cause severe sepsis and mortality, especially in susceptible populations. Our study focused on neurological involvement and severe invasive forms of listeriosis. Neuroinvasive forms were the most important risk factors for severe illness but not for mortality.

The 5-Ws of immunotherapy in head and neck cancer.

The immune checkpoint inhibitors, a class of drugs able to block immune suppressive pathways in order to prime an anticancer immunity, revolutionized standard of care in platinum-refractory recurrent and/or metastatic head and neck carcinoma (R/M HNSCC). The PD-1/ PD-L1 axis is involved in the genesis, maintenance and progression of HNSCC and represents the target of checkpoint inhibitors. HNSCC is an immunosuppressive disease with a high inflammatory component in tumor microenvironment. Recent clinical trials showed that only a small subset of patients really benefits from immunotherapy. This review aims to highlight the five W-points of immunotherapy: why immunotherapy is promising in HNSCC, what is currently available in daily clinical practice, when immunotherapy can be integrated into the therapeutic strategy, where it can be useful according to predictive response biomarker, who, among patients, could get the best benefit from immunotherapy and how improve the achieved results.