Altered Immune Status Research Articles

English

Diabetics exhibit a great frequency and severity of infection.Recovery of multidrug resistant Pseudomonas aeruginosa and ESBL producing Klebsiella and Escherichia coli are of serious concern. AIMS AND OBJECTIVES: The aims of the study are to establish the Bacteriological profile in Wagner's grades of foot ulcers in Diabetics and foot ulcers in Non-diabetics, Antibiogram of isolates. MATERIAL AND METHODS: A total of 265 samples were collected from two Study Groups. Pseudomonas aerugionasa isolates were subjected to screening of Amp - C β lactamase by disc antagonism test.Klebsiella species and Escherichia coli that were found to be resistant to first, second and third generation cephalosporins were confirmed for ESBL production by Disc Potentiation Test. RESULTS: More number of ulcers (111) were of Grade II in diabetics and the commonest risk factor was found to be Neuropathy (122). Nature of infection in foot ulcers was mostly polymicrobial (35.8%) in Diabetics where as it was only Monomicrobial (100%) in Non-diabetics. All the CONS isolated (59) from diabetic foot ulcers were sensitive to Linezolid and resistant to Penicillin. They were moderately resistant to Cephalosporins (68%) and Fluoroquinolones (59%).Ten of Escherichia coli (32.2%) and 26 of Klebsiella species (44.0%) were ESBL producers. 18 of Pseudomonas spp (27.2%) were positive for Amp C beta lactamase. CONCLUSION: Because of Neuropathy and the altered immune status in Diabetic patients, opportunistic and polymicrobial infections are common in Diabetic foot ulcers. Moreover these patients show Multi Drug Resistant patterns.

Identification and sequence analysis of Tapasin gene in guinea fowl

Aim: An attempt has been made to identify and study the nucleotide sequence variability in exon 5 - exon 6 regions of guinea fowl Tapasin gene. Materials and Methods: Blood samples were collected from randomly selected birds (12 guinea fowl birds) and Tapasin gene amplified using chicken specific primers designed from GenBank submitted sequences. Polymerase chain reaction conditions were standardized so as get only single amplicons. Obtained products were then cloned and sequenced; sequences were then analyzed using suitable software. Results: Amplicon size of the Tapasin gene in guinea fowl was same as reported in chicken with areas of transitions and transversions. The sequence variations reported in these coding sequences might have influence in the protein structure, which may be correlated with the increased immune status of the bird when compared with chicken breeds. Conclusion: Since Tapasin gene is an immunologically important gene, which plays an important role in the immune status of the bird. Sequence variations in the gene can be correlated with the altered immune status of the bird.

Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection.

Vitamin D has been recognised as a potent immunomodulator and its deficiency is common in different population groups including patients with diabetic foot infection. Diabetic foot infection reflects the altered immune status of the host. As cytokine regulation plays a significant role in infection and wound-healing processes, the present study aimed to evaluate the association between vitamin D status and inflammatory cytokine profiles in patients with diabetic foot infection. The serum concentrations of vitamin D (25-hydroxyvitamin D), IL-1β, IL-6, TNF-α and interferon-γ (IFN-γ) were measured in 112 diabetic foot infection cases and 109 diabetic controls. Severe vitamin D deficiency (25-hydroxyvitamin D concentration < 25 nmol/l) was more common in cases than in controls (48.2 v. 20.5%). Although age, duration of diabetes, HbA1C (glycosylated Hb) concentration and BMI were similar, cases had significantly higher concentrations of IL-6 (P≤ 0.001), IL-1β (P≤ 0.02) and TNF-α (P≤ 0.006) than controls. A significant negative correlation was also observed between 25-hydroxyvitamin D concentration and circulating concentrations of IL-1β (r -0.323; P≤ 0.001) as well as IL-6 (r -0.154; P≤ 0.04), but not between 25-hydroxyvitamin D and TNF-α and IFN-γ concentrations. Furthermore, a significant difference in IL-1β (P≤ 0.007) and IL-6 (P≤ 0.02) concentrations was observed in patients with severe 25-hydroxyvitamin D deficiency compared with patients with 25-hydroxyvitamin D concentration ≥ 25 nmol/l, and this difference was remarkable for TNF-α. In conclusion, severe vitamin D deficiency is associated with elevated inflammatory cytokine concentrations in diabetic patients, particularly in those with foot infection. A 25-hydroxyvitamin D concentration value < 25 nmol/l is suggested as the 'cut-off' for such immunological alterations in patients with diabetes mellitus.

Responses of the spleen to intraamniotic lipopolysaccharide exposure in fetal sheep.

Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis. Fetal sheep were exposed to IA LPS 5, 12, and 24 h and 2, 4, 8, or 15 d before delivery at 125 d of gestational age (term = 150 d). Splenic cytokine mRNA levels and cleaved caspase-3, CD3, and Foxp3 expression were evaluated. IA LPS increased interleukin (IL)1, IL4, IL5, and IL10 mRNA by twofold 24 h after injection. Interferon gamma increased by fivefold, whereas IL23 decreased 15 d post-LPS exposure. Cleaved caspase-3-positive cells increased 2 and 8 d after LPS exposure. CD3 immunoreactivity increased within 5 h with increased Foxp3-positive cells at 12 h. Intrauterine inflammation induced a rapid and sustained splenic immune response with persistent changes in the cytokine profile. This altered immune status may drive sustained inflammation and injury in other fetal organs.

Squamous Cell Cancer of the Rectum: A Case Report

Introduction: Primary squamous cell carcinoma (SCC) of the colon and rectum are rare malignancies accounting for less than 0.025% of all colonic malignancies. Most reported cases were strongly associated with HIV positive state, immunosuppressive therapy, inflammatory bowel diseases (IBD), and other chronic disease states. Mucosal metaplasia is believed to be the leading cause of this form of carcinoma. We present a patient with squamous cell carcinoma of the lower rectum who underwent neoadjuvant chemoradiation therapy and planned for abdominoperineal resection. A 72-year-old female presented for bright red blood per rectum. The patient had 6-7 bloody bowel movements before her presentation. She was also complaining of a “naggy” abdominal pain. She was hemodynamically stable and her physical exam was unremarkable. A colonoscopy was performed, which revealed a large malignant-appearing mass in the lower rectum at about 1 cm from the anal verge measuring at least 5 cm in size. Also, 2 flat polyps were found. Polypectomy was done and biopsies were taken. Given the large malignant-appearing rectal mass, a flexible sigmoidoscopy with endoscopic ultrasound was performed that demonstrated a 6x5-cm ulcerated mass in the distal rectum, located 1 cm above the anal margin staged initially to be T3N0M0. The pathology reported moderately differentiated squamous cell carcinoma. An extensive work-up did not show any other lesions in the chest or in the abdomen. However, a PET scan highlighted multiple liver lesions, but the ultrasound-guided FNA of 1 of these lesions came back negative for malignancy. Based on the pathology report, and given the very distal location of the rectal mass, the plan was to start with a neoadjuvant chemoradiation therapy followed by an abdominoperineal resection. Squamous cell carcinoma of the rectum is an extremely rare histopathological entity. Many questions regarding its histogenesis and biological behaviour remain unanswered, but several hypotheses have been suggested, including human papilloma virus infection, chronic underlying inflammatory disease processes, or altered immune status. Gynecological cancer is an important differential diagnosis in females with involvement of the genital organs. Nowadays, surgery is the treatment method of choice, and adjuvant radiation and chemotherapy are recommended in advanced stages of the disease. With a greater awareness among surgeons and pathologists, more cases may become known, leading to a better understanding of this tumor’s behavior.

MNos2 deletion and human NOS2 replacement in Alzheimer disease models.

Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

Altered immune status of circulating T lymphocytes during sepsis: children also.

Altered immune status of blood leukocytes is a general phenomenon observed in adult patients with sepsis or septic shock. This is also the case in children with septic shock for both T helper 1 and T helper 2 lymphocytes, as demonstrated by their reduced ex vivo cytokine production upon activation by phytohemagglutinin.

Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss

The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

Host immune status and response to hepatitis E virus infection.

Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available.

Quantitative Defects Of Cellular Immune Responses In Patients With Newly-Diagnosed Diffuse Large B-Cell Lymphoma

Altered immune status in non-Hodgkin lymphoma is characterized by undesired autoimmune phenomena and frequent occurrence of infections. The immune defects may be responsible for the initiation, maintenance and progression of malignant clone. We therefore evaluated immune effector cells between 35 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and 34 age- and sex- matched healthy controls using three-color flow cytometry. For patients with DLBCL, there were 19 males and 16 females with a mean age of 59.9 ± 15.6 years. There were 6, 17 and 13 patients with ECOG &gt; 2, stage III-IV and high intermediate to high International Prognostic Index, respectively. We found significant decreases in CD3+CD4+, CD4/CD8 ratio, CD4 central memory (CD4+CD45RO++CD27+) and B cells (Figure 1). From conditional logistic regression, only CD4/CD8 ratio showed significant association with being cases with the odds ratio of 0.29 (95% CI 0.12, 0.68). Disclosures: No relevant conflicts of interest to declare.

Could Infection Effect Cognitive Function in Schizophrenia ? : One Egyptian Center Study

ackground: Numerous viral infections, in utero or in childhood, have been associated with an increased risk of later developing schizophrenia. This may be explained by chronic infections or an altered immune status. Objectives: The present study aimed to measure levels of serum antibodies to some infectious agents in a sample of Egyptian patients with schizophrenia and to assess if there is correlation of cognitive functioning with this serum titer. Methods: the Arabic Version of Wechsler Adult Intelligence Scale Revised; selected subtests from Wechsler Memory Scale-Revised; Trail making test and Self-Assessment Scale of Cognitive Complaints in Schizophrenia were used to assess cognitive function in 102 newly diagnosed drug naive patients with schizophrenia and 124 healthy matched individuals. Solid phase enzyme immuno-assay (EIA) techniques were used to measure IgG class antibodies to Rubella virus, cytomegalovirus (CMV), Herpes simplex virus type 1&2 (HSV-1&2), and to Toxoplasma gondii (T. gondii) in the sera of the study individuals. Associations between serological exposure to selected infectious agents and cognitive function in schizophrenia were evaluated. Results: All studied infectious agents were more prevalent in patients with schizophrenia than in the control group. Higher anti-HSV1&2, and anti-Rubella IgG antibodies titers were significantly correlated with impaired cognitive tests, while anti-T. gondii IgG titer was insignificantly correlated with any of the neuro-cognitive tests. Conclusions: The higher prevalence of serum IgG antibodies to all analyzed infectious agents with higher titers within patients with schizophrenia emphasizes a possible role of infectious agents in the etiopatho-genesis of schizophrenia. The data indicates that not one specific agent might be responsible for schizophrenic symptoms. Impairment of the cognitive functions in patients with schizophrenia was associated with higher IgG titers to HSV1&2, and Rubella virus.

Differential microRNA expression in blood in multiple sclerosis

Background: microRNAs (miRNAs) regulate the expression of the genome at the post-transcriptional level. They play a role in autoimmunity and inflammation, and show potential for use as therapeutic targets in many diseases. With the recent detection of miRNAs in body fluids, the possibility for using miRNAs as diagnostic biomarkers has emerged. Objective: We assessed whether miRNAs contribute to the altered immune activation state in relapsing–remitting multiple sclerosis (RRMS) patients and investigated the possible use of miRNAs as diagnostic biomarkers in multiple sclerosis (MS). Methods: We performed global miRNA expression profiling analysis in peripheral blood mononuclear cells (PBMCs) and selected miRNAs were measured in plasma. We detected expression of miRNAs by real-time qPCR and compared results with cytokines related to inflammation and disease activity. Selected miRNAs were analyzed in PBMC subpopulations, after isolating them by magnetic bead separation. Results: We found that among validated miRNAs, let-7d correlated with the pro-inflammatory cytokine interleukin-1B. The miR-145 was 3-fold up-regulated in MS patients; its possible use as a diagnostic biomarker in PBMCs, plasma and serum was confirmed by ROC-curve analysis (Area under the curve (AUC) 0.785, p = 0.0004; 0.785, p = 0.004; 0.981, P < 0.0001, respectively). Conclusions: RRMS patients in remission had altered expression of miRNAs. We validated miR-145 as a potential diagnostic biomarker for the diagnosis of MS in blood, plasma and serum.

Blood Biomarkers Could Aid Prediction of Psychosis Risk

Blood Biomarkers Could Aid Prediction of Psychosis Risk

Immunological profile of Fanconi anemia: A multicentric retrospective analysis of 61 patients

In this study, the immunological status of 61 patients with Fanconi anemia (FA) with advanced marrow failure before hematopoietic stem cell transplantation was analyzed by assessing the phenotype of peripheral blood lymphocytes, serum immunoglobulin (Ig) levels, and inflammatory cytokines. In patients with FA, total absolute lymphocytes (P < 0.0001), B cells (P < 0.0001), and NK cells (P = 0.003) were reduced when compared with normal controls. T cells (CD3), that is, cytotoxic T cells, naïve T cells, and regulatory T cells, showed a relative increase when compared with controls. Serum levels of IgG (P < 0.0001) and IgM (P = 0.004) were significantly lower, whereas IgA level was higher (P < 0.0001) than in normal controls. TGF-β (P = 0.007) and interleukin (IL)-6 (P = 0.0007) levels were increased in the serum of patients when compared with controls, whereas sCD40L level decreases (P < 0.0001). No differences were noted in the serum levels of IL-1β, IL-2, IL-4, IL-10, IL-13, IL-17, and IL-23 between FA subjects and controls. This comprehensive immunological study shows that patients with FA with advanced marrow failure have an altered immune status. This is in accordance with some characteristics of FA such as the proinflammatory and proapoptotic status. In addition, B lymphocyte failure may make tight and early immunological monitoring advisable.

Late onset invasive pneumococcal disease in a liver transplanted patient: beyond the Austrian syndrome

Invasive disease caused by Streptococcus pneumoniae is a major cause of morbidity and mortality in high-risk individuals with severe comorbidities, including asplenia, chronic alcoholism, and altered immune status. The risk of invasive pneumococcal disease has been significantly higher in transplant patients compared with the general population. Here, we report an unusual case of a disseminated pneumococcal infection with meningitis, endocarditis, spondylodiscitis, and muscle abscess in an asplenic patient on chronic immunosuppressive therapy for liver transplantation performed 17years before.

Pathogenesis in immune thrombocytopenia: new insights.

Idiopathic (immune) thrombocytopenic purpura (ITP) is a common autoimmune disorder resulting in isolated thrombocytopenia. ITP can present either alone (primary) or in the setting of other conditions (secondary) such as infections or altered immune states. ITP is associated with a loss of tolerance to platelet antigens and a phenotype of accelerated platelet destruction and impaired platelet production. Although the etiology of ITP remains unknown, complex dysregulation of the immune system is observed in ITP patients. Antiplatelet antibodies mediate accelerated clearance from the circulation in large part via the reticuloendothelial (monocytic phagocytic) system. In addition, cellular immunity is perturbed and T-cell and cytokine profiles are significantly shifted toward a type 1 and Th17 proinflammatory immune response. Further clues into immune dysregulation in ITP may be gleaned from studies of secondary ITP. Some infections can induce antiplatelet Abs by molecular mimicry, and there may be common elements involved in breaking tolerance with other autoimmune disorders. There is also evidence for a genetic predisposition to both ITP and responsiveness to therapy, which may in part lie within immune-related genes. Lastly, treatment with immunomodulatory agents remains the mainstay of ITP therapies.

Pathogenesis in immune thrombocytopenia: new insights

AbstractIdiopathic (immune) thrombocytopenic purpura (ITP) is a common autoimmune disorder resulting in isolated thrombocytopenia. ITP can present either alone (primary) or in the setting of other conditions (secondary) such as infections or altered immune states. ITP is associated with a loss of tolerance to platelet antigens and a phenotype of accelerated platelet destruction and impaired platelet production. Although the etiology of ITP remains unknown, complex dysregulation of the immune system is observed in ITP patients. Antiplatelet antibodies mediate accelerated clearance from the circulation in large part via the reticuloendothelial (monocytic phagocytic) system. In addition, cellular immunity is perturbed and T-cell and cytokine profiles are significantly shifted toward a type 1 and Th17 proinflammatory immune response. Further clues into immune dysregulation in ITP may be gleaned from studies of secondary ITP. Some infections can induce antiplatelet Abs by molecular mimicry, and there may be common elements involved in breaking tolerance with other autoimmune disorders. There is also evidence for a genetic predisposition to both ITP and responsiveness to therapy, which may in part lie within immune-related genes. Lastly, treatment with immunomodulatory agents remains the mainstay of ITP therapies.

Mycobacterium chelonae hand infection following ferret bite

We present a case of hand infection caused by Mycobacterium chelonae. The patient was a 58-year-old woman with Type II diabetes mellitus and stage 4 chronic kidney disease. The infection occurred following a ferret bite and had not responded to oral antibiotics in the primary care setting. She developed signs of pyogenic flexor tenosynovitis of the index and middle fingers of her left hand. Laboratory parameters showed high C-reactive protein, raised erythrocyte sedimentation rate and leucocytosis. Ultrasound imaging confirmed the clinical diagnosis. Plain radiographs showed no osseous involvement. The infection was treated with surgical debridement and broad spectrum parenteral antibiotics. The intra-operative tissue specimens were initially negative on aerobic and anaerobic cultures. Following transient improvement of her inflammatory parameters and clinical signs, she developed a recurrence with added features of osteomyelitis of the index and middle finger metacarpal heads on repeat radiographs. A revision surgical debridement of the flexor tenosynovitis and osteomyelitis with specific long-term antibiotic cover has led to resolution of the infection. Extended cultures of the tissue specimens at the regional laboratory confirmed the causative organism to be M. chelonae. To our knowledge, this is the first reported case of M. chelonae infection resulting from a ferret bite. This case reminds us of the need for a high index of suspicion for infection with uncommon pathogens following animal bites, especially in patients with altered immune status.

Tuberculosis in nephrotic syndrome and chronic kidney disease: an appraisal

Tuberculosis (TB) affects man at all ages with its protean manifestations and children with renal diseases are no exception to it. Owing to altered immune status in nephrotic syndrome and chronic kidney disease (CKD), TB can be a very common co-morbid condition in endemic nation like India. The onset can be very insidious and subtle mimicking the primary condition especially in CKD and the diagnosis remains a challenge. A high index of suspicion usually guides the clinician to diagnose the condition. The basic modalities of diagnosis remain same as in general population yet the results have to be interpreted in the light of primary renal condition. The article tries to envisage the diagnosis and management of TB in children with concomitant CKD and nephrotic syndrome.

Exciting Developments in the Immunology of Fungal Infections

The last decade has brought significant advances in our understanding of antifungal immunity, which offer hope for the development of novel immunotherapeutics. In this commentary, we provide a snapshot of the protective innate and adaptive components of antifungal immunity and highlight several recent topics of interest, placing in context the three associated reviews in this issue of Cell Host & Microbe.