Immunodeficiency Type Research Articles

65 Year Old Patient with Common Variable Immunodeficiency: 3 Years Followup and Development of Lung Adeno Carcinoma, is it a Coincidence?

Common variable immunodeficiency(CVID) is a type of primary humoral immunodeficiency which is generally diagnosed at childhood. Recurrent sinopulmonary infections are early presentations of disease. Some of the patients are diagnosed in adulthood. In addition to frequent infections, autoimmune phenomena may occur in about 22% of patients. Most common autoimmune findings are autoimmune rombocytopenic purpura, hemolytic anemia rheumatoid arthritis and sicca syndrome. Splenomegaly, granulomatous infiltrations, lymphadenopathy may be seen in the course of the disease. Increased risk of malignancies is reported in CVID. Hodgkin lymphoma, most common, intestinal and uterine adeno carcinoma and rarely neuroendocrine tumors are reported with CVID. We report a 65 year-old woman who had diagnosed as rheumatoid artritis, Sjogren syndrome and idiopathic thrombocytopenic purpura. She wasdiagnosed as CVID at the age of 65. After IVIG therapy, rheumatologic diseases had stabile course, but she was diagnosed lung adenocarcinoma 3 year after her diagnosis.

Transethmoidal nasal meningocele and CSF fistula in a child with recurrent bacterial meningoencephalitis

Background Recurrent bacterial meningitis in children poses a considerable diagnostic challenge due to its multiple etiologies. Making an early diagnosis is crucial in preventing further episodes that could lead to a potentially life threatening condition, neurologic sequelae and psychological trauma due to multiple invasive investigations. Recurrent bacterial meningitis has multiple underlying conditions, but it is most frequently caused by anatomic intracranial or lumbosacral defects (encephaloceles, meningocele, temporal bone malformations, skull fracture, dermoid cyst of the lumbosacral spine). Other predisposing conditions are different types of immunodeficiency (immunoglobulin deficiency, complement deficiency, HIV, asplenia) and chronic infections of the middle ear and paranasal sinuses.

Immunoglobulin replacement therapy for primary immunodeficiencies.

Exogenous antibody therapy to protect patients against infections and toxins is over 100 years old, yet progress continues to be made in the manufacture, administration and application of this type of immunotherapy, known as therapeutic human immunoglobulin. For the majority of patients with primary immunodeficiencies, immunoglobulin replacement is the only life-saving therapy and treatment is life-long, since the vast majority of primary immunodeficiency patients have primary antibody failure. Successful treatment depends on multiple factors: the availability of products, the type of immunodeficiency and any comorbidities of the individual patient. Essential components include long-term follow-up, regular monitoring and a close relationship between the patient and the multidisciplinary clinical immunology team. In this article, we describe the current immunoglobulin products and the types of adverse reactions. We provide evidence for clinical decision-making regarding dosing, route of administration and location of therapy, highlighting current 'best practice' recommendations.

A fractional-order model of HIV infection: Numerical solution and comparisons with data of patients

In this paper, a fractional-order model which describes the human immunodeficiency type-1 virus (HIV-1) infection is presented. Numerical solutions are obtained using a generalized Euler method (GEM) to handle the fractional derivatives. The fractional derivatives are described in the Caputo sense. We show that the model established in this paper possesses non-negative solutions. Comparisons between the results of the fractional-order model, the results of the integer model and the measured real data obtained from 10 patients during primary HIV-1 infection are presented. These comparisons show that the results of the fractional-order model give predictions to the plasma virus load of the patients better than those of the integer model.

Long-lasting production of new T and B cells and T-cell repertoire diversity in patients with primary immunodeficiency who had undergone stem cell transplantation: a single-centre experience.

Levels of Kappa-deleting recombination excision circles (KRECs), T-cell receptor excision circles (TRECs), and T-cell repertoire diversity were evaluated in 1038 samples of 124 children with primary immunodeficiency, of whom 102 (54 with severe combined immunodeficiency and 48 with other types of immunodeficiency) underwent hematopoietic stem cell transplantation. Twenty-two not transplanted patients with primary immunodeficiency were used as controls. Only data of patients from whom at least five samples were sent to the clinical laboratory for routine monitoring of lymphocyte reconstitutions were included in the analysis. The mean time of the follow-up was 8 years. The long-lasting posttransplantation kinetics of KREC and TREC production occurred similarly in patients with severe combined immunodeficiency and with other types of immunodeficiency and, in both groups, the T-cell reconstitution was more efficient than in nontransplanted children. Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period. However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire. Overall, our data suggest that long-term B- and T-cell reconstitution was equally achieved in children with severe combined immunodeficiency and with other types of primary immunodeficiency.

Pulmonary tuberculosis in patients with chronic renal failure at Zagazig University Hospitals

The incidence of active TB and attendant mortality is increased in patients with impaired cellular immunity, such as HIV infected patients, solid organ and stem cell transplant recipients and patients with end-stage renal failure. The relative risk for TB varies with the type of immunodeficiency and mortality rates may be as high as 75%. End-stage renal disease (ESRD) and particularly uraemia is a known contributor to immunosuppression. The aim of this workThe aim of this work was to evaluate the increasing risk of pulmonary tuberculosis among patients with chronic renal failure and the impact of hemodialysis. Patients and methodsThis study was carried at both Nephrology Unit and Chest Department, Zagazig University Hospitals during the period from April 2012 to Jan 2013. The study included a total number of 140 patients with chronic renal failure (92 males and 48 females), with mean age of 49±6.4years. Patients were classified to three groups: Group 1: Included 40 Patients with chronic renal failure and not on dialysis. Group 2: Included 50 Patients with chronic renal failure and on regular hemodialysis three sittings per week for less than 1year. Group 3: Included 50 Patients with chronic renal failure and on regular hemodialysis three sittings per week for more than 1year. All patients were subjected to: history taking and medical evaluation including general and local examinations, routine laboratory investigations, Plain chest X-ray; Posteroanterior and lateral views for all patients, Sputum Ziehl–Neelsen staining and Sputum induction in patients who had chest X-ray suspecting pulmonary TB without expectoration and Tuberculin skin testing. Selected cases were subjected to fiberoptic bronchoscopy to obtain BAL for ZN staining. Results16 patients (11.4%) proved to have pulmonary tuberculosis by +ve ZN stain for acid fast bacilli in either sputum or BAL, 28 patients (20%) were suspected to have pulmonary tuberculosis by radiological suspension and −ve sputum ZN for acid fast bacilli, 6 patients (4.3%) proved to have extra-pulmonary TB while 90 patients (64.3%) were free from tuberculosis. There were no significant differences among different groups as regards infection by TB. ConclusionPatients with chronic renal failure are at increased risk for pulmonary and extra pulmonary tuberculosis and should be screened routinely and carefully for early detection of TB infection.

Фактори вродженого та адаптивного місцевого імунітету в дітей із первинними дефіцитами антитілоутворення

У 40 дітей із різними варіантами первинних імунодефіцитів (ПІД) антитілоутворення ви­вчалися фактори місцевого імунітету в слині. Установлено, що в слині всіх дітей із ПІД антитілоутворення порівняно з імунокомпетентними дітьми концентрація факторів адаптивного імунітету суттєво знижена. Недостатність адаптивного імунітету при ПІД антитілоутворення деякою мірою компенсується збільшеним рівнем факторів вродженого імунітету на слизових оболонках — вільного Sc, а також лактоферину при вибірковому імунодефіциті IgA. При ПІД антитілоутворення спостерігається збільшення рівня TNF-α в слині, що може свідчити про персистенцію місцевого запалення на слизових оболонках респіраторного тракту.

Common variable immunodeficiency – case report

Common variable immunodeficiency (CVID) or acquired hypogammaglobulinemia is the type of primary immunodeficiency. Deregulation of the immune system, leading to hypogammaglobulinemia, defective activation and proliferation of T cells and dendritic cells, and malfunction of the cytokines are observed in CVID. The clinical picture of CVID varies, any organ or system can be affected, therefore the diagnosis is often difficult and delayed and sometimes is not always possible. This article describes a twelve years old boy with all the clinical signs of immunodeficiency, as confi rmed by laboratory. The main treatment consists of life-long immunoglobulin substitution in intravenous or subcutaneous form.

Impfen bei Immundefekten oder medikamentöser Immunsuppression

Patients with immunodeficiency and patients under immunosuppressive therapy have an increased risk of infectious diseases. Vaccination strategies are needed to protect them from preventable diseases. The underlying disease and severity of the immune impairment may have influence on indications and contra-indications of vaccines. Inactivated vaccines can be administered safely according to the current recommendations of the Permanent Commission on Vaccinations of the Robert-Koch-Institut in Berlin, Germany (STIKO). Depending on the severity of the immune dysfunction, antibody response to vaccinations varies. Where possible, the antibody response following vaccinations should be tested. Previously, attenuated live vaccines were considered to be strictly contra-indicated in immunocompromised patients. Today, the administration of attenuated live vaccines is thought to be possible, depending on the degree and type of immunodeficiency or immunosuppression of the individual.

Occurrence of autoantibodies for gastrointestinal autoimmune diseases in children with common variable immune deficiency and selected IgA deficiency.

IntroductionSelected IgA deficiency (IgAD) and common variable immune deficiency (CVID) are humoral immunity deficiencies frequent in children. In both these types of immunodeficiency, autoimmune diseases are present in 20–30% of patients, but the disease profiles are different between adults and children. Autoimmune diseases of the gastrointestinal tract (IBD) and celiac disease are typical for children with IgAD and CVID. Diagnosis is based on clinical symptoms, histology of jejunum and antibodies often preceding the onset of disease. However, the diagnosis of IBD and celiac disease is difficult in immune deficiency patients due to weaker or absent production of antibodies, and different jejunum histology, particular in CVID patients.AimDetection of antibodies for autoimmune diseases in children with diagnosis of CVID and IgAD.Material and methodsThe study included 43 children with CVID and 63 children with IgAD diagnosis. Antibodies typical for celiac disease (for endomysium, tissue transglutaminase and gliadin) were tested in IgA class (CVID patients), IgG class (IgAD, CVID patients) and found in 16 patients (3 – CVID, 13 – IgAD).ResultsAntibodies for IBD (for Saccharomyces cerevisiae antigen – ASCA, goblet cells – Gab, neutrophil’s cytoplasm – ANCA, pancreatic cells – Pab) were noted in 17 patients (7 – CVID, 10 – IgAD). Celiac disease was diagnosed in two children with mild and unspecific clinical symptoms followed by introduction of a gluten-free diet. The remaining children with present antibodies but without clinical symptoms involving the gastrointestinal tract are under careful clinical observation with antibody assay every 6 months.ConclusionsThe antibodies are produced despite impaired humoral immunity but the level might be low so the lower limit of positive results is postulated.

Fungal Infections in Immunocompromised Travelers

Immunocompromised patients represent an increasing group of travelers, for business, tourism, and visiting friends and relatives. Those with severe cellular immunodeficiency (advanced human immunodeficiency virus infection and transplant recipients) display the highest risk of fungal infections. International travel is less risky in most other types of immunodeficiency (except those with neutropenia). A systematic visit in a travel clinic for immunocompromised patients traveling to the tropics ensures that the specific risks of acquiring fungal infections (and others) are understood. When immunocompromised hosts return to their area of residence, a nonbacteriologically documented, potentially severe, febrile pneumonia, with or without dissemination signs (skin lesions, cytopenia) should alert for travel-acquired fungal infection, even years after return. Localized subcutaneous nodule may be also ascribed to fungal infection. Finally, infectious diseases physicians should be aware of major clinical patterns of travel-acquired fungal infection, as well as the fungi involved, and risk factors according to the geographical area visited.

Stem Cell Transplantation for Primary Immunodeficiency Disease: Experience of a Singapore Hospital

We retrospectively analyzed the outcomes of hematopoietic stem cell transplantation in 7 patients with primary immunodeficiency diseases treated at the National University Hospital, Singapore, over the period from December 1996 to January 2010. The primary immunodeficiency diseases managed were X-linked hyperimmunoglobulin M syndrome (n = 3), severe combined immunodeficiency (n = 1), leukocyte adhesion deficiency type 1 (n = 1), chronic granulomatous disease (n = 1), and Wiskott-Aldrich syndrome (n = 1). The age of the patients ranged from 5 months to 17 years. Conditioning regimen depended on the type of immunodeficiency, whereas supportive treatment was tailored for differing pretransplant conditions. Eight stem cell transplantations were performed for 7 patients. Donors were HLA-matched sibling donors for 2 patients and unrelated donors for the rest. At the median follow-up of 8.6 years (range 2.2-15.0 years) as of December 2011, 6 patients were alive and cured of their primary diseases.

Severe adverse reactions after vaccination with Japanese BCG vaccine: a review

Japanese BCG vaccine has been admitted by the quality control of World Health Organization (WHO) as the safest BCG vaccine in the world. Even though, BCG, as a live bacterial vaccine, inevitably causes dissemination beyond vaccination site and regional lymph-nodes to various part of the body under certain special conditions. We tried to review the clinical features and immunological status of the cases in which "severe" adverse reactions had developed after vaccination with Japanese freeze-dried BCG vaccine prepared from BCG substrain Tokyo. "Severe" adverse reaction was arbitrarily defined as the adverse reactions of clinical significance developed beyond vaccination site and regional ipsilateral axillary lymph-nodes. By the extensive search of the literatures, 39 cases were identified since 1951 when vaccination with freeze-dried BCG vaccine became compulsory by the Tuberculosis Prevention Law in Japan. Incidence rate was calculated as 0.0182 cases per 100,000 vaccinations. Clinical manifestations of bone and joint were reported in 27 cases (multiple sites: 15 cases, single site: 12 cases), abnormalities in chest X-ray in 13 cases, skin manifestations in 17 cases, diseases in other sites or organs in 8 cases. Most of the cases had lesions in multiple organs. Among these 39 cases, 13 had been diagnosed to have some types of primary immunodeficiency (5 cases: chronic granulomatous disease (CGD); 4 cases: severe combined immunodeficiency (SCID); 4 cases: IFN-gamma receptor 1 deficiency). Further, unidentified defects in cellular immunity were reported in other 6 cases. Death was reported in 6 cases, but in two cases the causes of death were the infections due to different pathogens, namely, pulmonary abscess due to Staphylococcus sp. and bacteremia due to Pseudomonas aeruginosa, respectively, and in only one case death was evidenced as due to disseminated BCG infection by autopsy. All of 6 death cases had some type of immunodeficiency. Apart from fatal cases, outcome of "severe" adverse events were generally favorable and they were successfully treated by anti-tuberculosis therapy with or without surgical treatment for bone and joint lesions. Because the risk of "severe" adverse reactions is high among those of primary immunodeficiency, so it is advisable to avoid BCG vaccination during the first three months after birth when the detection of immunodeficiency is practically impossible.

Store-operated CRAC channels: function in health and disease

Elevation of cytosolic Ca(2+) levels through the activation of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels is involved in mediating a disparate array of cellular responses. These include secretion, metabolism and gene expression, as well as cell growth and proliferation. Moreover, emerging evidence points to the involvement of aberrant CRAC channel activity in human diseases, such as certain types of immunodeficiency and autoimmunity disorders, allergy, and inflammatory bowel disease. This article summarizes recent advances in understanding the gating and function of CRAC channels, their links to human disease and key issues for the development of channel blockers.

Maxiprep genomic DNA extractions for molecular epidemiology studies and biorepositories

Molecular epidemiology and genomic characterisation studies require the screening of large numbers of individuals to achieve statistical significance. Although many of the novel DNA extraction methods offer convenient, high-throughput capabilities, their use for the processing of larger sample volumes becomes very expensive. We are currently compiling the Mexican Genomic DNA Collection in order to address specific health priorities through molecular techniques. Our approach employs a low-cost laundry detergent based DNA extraction technique that maximizes DNA yield and quality. We have optimised four different modalities (maxiprep, midiprep, miniprep and microprep) for two different sources (leukocyte concentrates and whole blood). Our optimised protocol produces 4.5 mg of DNA from 15 ml of blood-bank discarded leukocyte concentrates with spectrophotometric quality, genomic integrity and PCR suitability that rivals that of phenol-chloroform extracted samples. We present evidence of many PCR applications that we have carried out on samples extracted with this technique including Killer-cell Immunoglobulin-like Receptor genotyping, Short Tandem Repeat profiling as well as nucleic acid screening for hepatitis B and human immunodeficiency type-1 viruses. This paper highlights many of the advantages that this DNA extraction technique provides over existing methodologies, whether it is used to establish large genomic DNA collections (as was our main intention) or as a routine DNA extraction method for PCR applications.

First report of the absence of viral load in testicular sperm samples obtained from men with hepatitis C and HIV after washing and their subsequent use

Human immunodeficiency virus and hepatitis C infections are sexually transmitted diseases that require sperm samples to be pretreated to eliminate the viral presence before their safe use in assisted reproduction treatments. In this report we describe our experience with sperm washing protocols applied to sperm cells from testicular biopsies as well as the results obtained in subsequent assisted reproduction treatments on seropositive males that are also azoospermic.

Low-level HIV-1 replication and the dynamics of the resting CD4+T cell reservoir for HIV-1 in the setting of HAART

BackgroundIn the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells.MethodsHere we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART.ResultsBy comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model.ConclusionThe intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.

Human immunodeficiency type-1 virus (HIV-1) infection in serodiscordant couples (SDCs) does not have an impact on embryo quality or intracytoplasmic sperm injection (ICSI) outcome

To evaluate the embryo quality in our program for human immunodeficiency type-1 virus (HIV-1) serodiscordant couples (SDCs) with the male infected in comparison with a tubal-factor infertility control group. Retrospective case-control study. Instituto Valenciano de Infertilidad, Valencia, Spain. Thirty SDC and 79 control couples without HIV-1 infection attending for intracytoplasmic sperm injection (ICSI). Only first cycles were considered. Controlled ovarian hyperstimulation and ICSI in both groups; sperm wash, nested polymerase chain reaction (PCR) in semen sample, and capacitation by swim-up after thawing the semen sample in the SDC group; and sperm capacitation by swim-up after thawing the semen sample in the control group. ICSI procedure and embryo characteristics (fertilization, cleavage, embryo morphology, and development) and cycle outcome (ongoing pregnancy and miscarriage rates). Fertilization and cleavage rates were similar between the groups. On days 2 and 3 of embryo development, very similar embryo features were found between the groups. There was no difference in mean number of optimal embryos on day 3. When embryos were cultured up to 5-6 days, a significant increase in embryo blockage was found in the SDC group compared with the control group. The mean number of optimal blastocysts on day 6 was comparable in both groups. No difference was found regarding the number of cryopreserved and transferred embryos or implantation, pregnancy, multiple pregnancy, or miscarriage rates between the groups. HIV-1 infection in SDCs with infected males does not appear to have a significantly negative impact on embryo development or ICSI outcome.

Estimation of Human Herpesvirus 8 Prevalence in High-Risk Patients by Analysis of Humoral and Cellular Immunity

Immunocompromized individuals, such as patients with end-stage renal disease, transplant recipients, and HIV-infected patients, are at increased risk of acquiring human herpesvirus (HHV)-8 associated infectious complications. The prevalence of HHV-8 infection generally is determined by detection of immunoglobulin G. However, because serological assays differ greatly, estimations on the actual HHV-8 prevalence vary considerably. HHV-8-specific cellular and humoral immunity were analyzed in 128 controls, 73 patients on dialysis, 67 transplant recipients, and 69 HIV-infected patients with the use of flow cytometry and indirect immunofluorescence microscopy. A higher seroprevalence (from 13.7% to 44.9%) was confirmed for all groups of immunocompromised individuals as compared with healthy controls (3.9%). Among immunocompetent individuals, as little as 12.5% had HHV-8 reactive T-cell frequencies greater than the detection limit. In line with a higher seroprevalence in immunosuppressed patients, HHV-8-specific T cells were detectable in 30.1% of dialysis patients, 20.9% of transplant recipients, and 24.6% of HIV-infected individuals. When combining the individual presence of either HHV-8-specific antibodies or T cells or both, the prevalence of HHV-8 infection approached 15.6% in healthy individuals and 41.1%, 40.3%, and 55.1% in dialysis patients, transplant recipients, and HIV-infected individuals, respectively. The exclusive serological analysis considerably underestimates the prevalence of HHV-8 infection in all study groups. Thus, the combined quantitation of both humoral and cellular immunity may instead be a superior method to assign the individual HHV-8 status. Moreover, this study suggests that the relative contributions of humoral and cellular immunity in control of HHV-8 may be different depending on the type of immunodeficiency.

Pulmonary and Sinusal Changes in 45 Patients With Primary Immunodeficiencies

The aims of the study were 1) to identify and quantify pulmonary changes in subjects affected by agammaglobulinemia (AG), and common variable immunodeficiency (CVID) and 2) to assess the incidence, type, and degree of chronic sinusitis and their relation to pulmonary changes. Forty-five patients affected by AG (18) and CVID (27) underwent computed tomography of lungs and paranasal sinuses. Of 45 patients, 26 (57.7%) had pulmonary changes, more frequent among CVID than AG patients (P = 0.37). Bronchiectases were detected in 7 of 12 AG and in 9 of 14 CVID; the difference is not statistically significant (P = 0.53). Computed tomographic findings of chronic sinusitis were detected in 41 of 45 patients. There was no statistically significant difference between AG and CVID patients. Bronchial and sinusal abnormalities did not correlate in 11 patients followed longitudinally. On computed tomography, the type and severity of lung lesions do not correlate either with the type of immunodeficiency or with the severity of the sinusal involvement.