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Acute Cervical Longitudinally Extensive Transverse Myelitis in a Child With Lipopolysaccharide-Responsive-Beige-Like-Anchor-Protein (LRBA) Deficiency: A New Complication of a Rare Disease.

Front Pediatr. 2020;8:580963

Authors: Chinello M, Mauro M, Cantalupo G, Talenti G, Mariotto S, Balter R, De Bortoli M, Vitale V, Zaccaron A, Bonetti E, Di Carlo D, Barzaghi F, Cesaro S

Abstract
Lipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder (PID) that can cause a common variable immunodeficiency (CVID)-like disease. The typical features of the disease are autoimmunity, chronic diarrhea, and hypogammaglobulinemia. Neurological complications are also reported in patients affected by LRBA deficiency. We describe a 7-year old female with an acute cervical longitudinally extensive transverse myelitis (LETM) as a feature of LRBA deficiency. This is the first case of LETM associated with LRBA deficiency described in literature.

PMID: 33178652 [PubMed]

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Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation.

Asia Pac Allergy. 2020 Oct;10(4):e37

Authors: Lai YW, Tan TC

Abstract
Good syndrome (GS) is a primary immunodeficiency (PID) that presents in middle aged to older adults with features of thymoma, hypogammaglobulinemia, CD4 T lymphopenia, inverted CD4/CD8+ ratio, and impaired T-cell mitogen proliferative responses. We present a patient, a 62-year-old female, who first presented with disease manifestation of acute hepatitis from hepatitis B virus (HBV) reactivation, which was subsequently complicated by recurrent hospitalizations for recurrent pneumonia and concomitant Helicobacter pylori and cytomegalovirus enteritis. She was later found to have thymoma and hypogammaglobulinemia and was diagnosed with GS. Although the well-known importance of T cell is in directing B-cell responses in the immunopathology of thymoma, low levels of natural killer and CD4+ γδ T cells may also be the cause of both low immune surveillance of tumor development and weak clearance of viral infection. Hence, the temporal sequence of opportunistic infections following HBV reactivation and thymoma discovery may reflect a loss of immune surveillance as the first manifestation of PID.

PMID: 33178562 [PubMed]

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Newborn Screening for SCID and Other Severe Primary Immunodeficiency in the Polish-German Transborder Area: Experience From the First 14 Months of Collaboration.

Front Immunol. 2020;11:1948

Authors: Giżewska M, Durda K, Winter T, Ostrowska I, Ołtarzewski M, Klein J, Blankenstein O, Romanowska H, Krzywińska-Zdeb E, Patalan MF, Bartkowiak E, Szczerba N, Seiberling S, Birkenfeld B, Nauck M, von Bernuth H, Meisel C, Bernatowska EA, Walczak M, Pac M

Abstract
In 2017, in the Polish-German transborder area of West Pomerania, Mecklenburg-Western Pomerania, and Brandenburg, in collaboration with two centers in Warsaw, a partnership in the field of newborn screening (NBS) for severe primary immunodeficiency diseases (PID), mainly severe combined immunodeficiency (SCID), was initiated. SCID, but also some other severe PID, is a group of disorders characterized by the absence of T and/or B and NK cells. Affected infants are susceptible to life-threatening infections, but early detection gives a chance for effective treatment. The prevalence of SCID in the Polish and German populations is unknown but can be comparable to other countries (1:50,000-100,000). SCID NBS tests are based on real-time polymerase chain reaction (qPCR) and the measurement of a number of T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and beta-actin (ACTB) as a quality marker of DNA. This method can also be effective in NBS for other severe PID with T- and/or B-cell lymphopenia, including combined immunodeficiency (CID) or agammaglobulinemia. During the 14 months of collaboration, 44,287 newborns were screened according to the ImmunoIVD protocol. Within 65 positive samples, seven were classified to immediate recall and 58 requested a second sample. Examination of the 58 second samples resulted in recalling one newborn. Confirmatory tests included immunophenotyping of lymphocyte subsets with extension to TCR repertoire, lymphoproliferation tests, radiosensitivity tests, maternal engraftment assays, and molecular tests. Final diagnosis included: one case of T-BlowNK+ SCID, one case of atypical Tlow BlowNK+ CID, one case of autosomal recessive agammaglobulinemia, and one case of Nijmegen breakage syndrome. Among four other positive results, three infants presented with T- and/or B-cell lymphopenia due to either the mother’s immunosuppression, prematurity, or unknown reasons, which resolved or almost normalized in the first months of life. One newborn was classified as truly false positive. The overall positive predictive value (PPV) for the diagnosis of severe PID was 50.0%. This is the first population screening study that allowed identification of newborns with T and/or B immunodeficiency in Central and Eastern Europe.

PMID: 33178177 [PubMed – in process]

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Failure of immunological competence: when to suspect?

J Pediatr (Rio J). 2020 Nov 08;:

Authors: Mariz FP

Abstract
OBJECTIVES: To draw physicians’ attention to the different warning signs of diseases of innate errors of immunity.
DATA SOURCES: A non-systematic review of the literature was carried out in the PubMed, LILACS, and SciELO databases, in addition to consultation of reference textbooks.
SUMMARY OF THE FINDINGS: It is known that the lack of immunological competence observed in patients with innate errors of immunity diseases causes particularly serious and/or recurrent infections. However, manifestations related to autoimmunity, inflammation, allergies, and neoplasms can also occur. Aiming at the early identification of these patients, a list of warning signs for innate errors of immunity was created, in which the need for intravenous antibiotics or prolonged antibiotics use to control infection, growth deficit, and positive family history for this group of diseases are considered the most sensitive. Regarding non-infectious manifestations, early onset, difficulty in controlling with the usual treatments, atypical presentations or association with other warning signs are noteworthy, and investigation for innate errors of immunity in these situations is recommended.
CONCLUSIONS: This article highlights the importance of considering this group of diseases even in the face of patients with non-infectious manifestations. Disclosure of innate errors of immunity diseases, especially to non-specialists, is essential for early diagnosis and, consequently, for the reduction of these patients’ morbidity and mortality.

PMID: 33176165 [PubMed – as supplied by publisher]

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Unknown Cytomegalovirus Serostatus in Primary Immunodeficiency Disorders: A New Category of Transplant Recipients.

Transpl Infect Dis. 2020 Nov 10;:

Authors: Forlanini F, Dara J, Dvorak CC, Cowan MJ, Puck JM, Dorsey MJ

Abstract
BACKGROUND: Cytomegalovirus (CMV) serostatus of recipient (R) and donor (D) influences hematopoietic stem cell transplant (HSCT) outcome. However, it is not a reliable indicator of CMV infection in primary immunodeficiency disorder (PIDD) recipients who are unable to make adequate antigen specific immunoglobulin (Ig) or who receive intravenous Ig (IVIg) prior to testing.
OBJECTIVE: Since no data exist on PIDD with unknown CMV serostatus, we aimed to evaluate the relationship between pre-HSCT recipient and donor serostatus and incidence of CMV infection in recipients with unknown serostatus.
METHODS: A retrospective analysis of all pediatric PIDD HSCTs (2007-2018) was performed at University of California San Francisco. Recipients were separated into categories based on pre-transplant serostatus: 1) seropositive (R(+)), 2) seronegative (R(-)), 3) unknown serostatus (R(x)). Patients with pre-HSCT active CMV viremia were excluded.
RESULTS: 90 patients were included, 69% male. The overall incidence of CMV infection was 20%, but varied in R(+), R(-), and R(x) at 80%, 0%, and 14%, (p-value=0.0001). Similarly, 5-year survival differed among groups, 60% R(+),100% R(-), and 90% of R(x) (p-value=0.0045). There was no difference in CMV reactivation by donor serostatus (p-value=0.29), however faster time to clearance of CMV was observed for R(x)/D(+) group (median 9.5 days (IQR 2.5-18), p-value=0.024).
CONCLUSION: We identify a novel group of recipients, R(x), with an intermediate level of survival and CMV incidence post-HSCT, when compared to seropositive and seronegative recipients. No evidence of CMV transmission from D(+) in R(-) and R(x) was observed. We believe R(x) should be considered as a separate category in future studies to better delineate recipient risk status.

PMID: 33169931 [PubMed – as supplied by publisher]

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[Important issues in long-term hematological cancer survivors].

Rinsho Ketsueki. 2020;61(9):1035-1047

Authors: Ishida Y

Abstract
A literature review of the data of hematological cancer survivors revealed that both the cumulative proportion and burden of late effects change according to the attained age, primary cancer, and type of treatment. I selected neurocognitive dysfunction, cardiovascular disease, endocrinological dysfunction, musculoskeletal dysfunction, subsequent immunodeficiency, and reproductive dysfunction as representative late effects. I accordingly explained the characteristics of secondary cancers as the most life-threatening late effects and compared the late effects between survivors who did and did not undergo hematopoietic stem cell transplantation, respectively. The main goals of my educational lecture are as follows: (1) to highlight important late effects in hematological cancer survivors and their risk factors; (2) to discuss primary secondary cancers and explain their characteristics (e.g., frequency, incubation periods, and risk factors); (3) to characterize late effects after hematopoietic stem cell transplantation; and (4) to use representative long-term follow-up guidelines if necessary.

PMID: 33162497 [PubMed – in process]

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PROMIS-29 survey confirms major impact of fatigue on health-related quality of life in common variable immunodeficiency.

Immunol Res. 2020 Nov 08;:

Authors: Zhang S, Kline M, Fuleihan RL, Consortium U, Scalchunes C, Sullivan KE, Jongco AM

Abstract
Health-related quality of life (HRQOL) is an emerging topic of interest in patients with immunodeficiency. Information about HRQOL in common variable immunodeficiency (CVID) is limited. The primary objective was to compare primary immunodeficiency disease (PIDD) patients with and without common variable immunodeficiency (CVID) on HRQOL domains using Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey data from the United States Immunodeficiency Network (USIDNET) registry. The primary endpoint variables were scores on 7 HRQOL domains. The USIDNET registry was used to select patients with baseline PROMIS-29 data collected between 2015 and 2018. Descriptive statistics, Fisher’s exact test, and Student’s two-sample t test were used to compare patients with CVID versus patients with non-CVID on demographic and clinical characteristics. The single-sample t test was used to compare sample means to the normed population mean of 50. A general linear model approach to multiple regression with backward selection was used to remove factors that did not contribute significant information to the multivariable models, while controlling for multiple testing. Potential explanatory variables included group (CVID/non-CVID), sex, age, and BMI. Among 184 PIDD patients, 146 (79%) were diagnosed with CVID. Patients had a mean (SD) age of 53 (13.8), were predominantly female (83%), and were Caucasian (98%). PROMIS-29 results revealed a significant effect of group (CVID/non-CVID) on the anxiety, fatigue, and social participation domains, with fatigue being the most statistically significant. Fatigue, anxiety, and social participation may be key factors influencing HRQOL among patients with CVID. Future prospective longitudinal studies using PROMIS-29 will be needed to confirm these findings and to determine the mechanisms through which these factors develop in CVID, and how they can be improved.

PMID: 33161558 [PubMed – as supplied by publisher]

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Differences of SARS-CoV-2 serological test performance between hospitalized and outpatient COVID-19 cases.

Clin Chim Acta. 2020 Nov 04;:

Authors: Wolf J, Kaiser T, Pehnke S, Nickel O, Lübbert C, Kalbitz S, Arnold B, Ermisch J, Berger L, Schroth S, Isermann B, Borte S, Biemann R

Abstract
BACKGROUND: Serological severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays differ in the target antigen specificity, e.g. of antibodies directed against the viral spike or the nucleocapsid protein, and in the spectrum of detected immunoglobulins. The aim of the study was to evaluate the performance of two different routinely used immunoassays in hospitalized and outpatient COVID-19 cases.
METHODS: The test characteristics of commercially available spike1 protein-based serological assays (Euroimmun, EI-assays), determining IgA or IgG and nucleocapsid-based assays (Virotech, VT-assays) determining IgA, IgM or IgG were compared in 139 controls and 116 hospitalized and outpatient COVID-19 cases.
RESULTS: Hospitalized COVID-19 patients (n=51; 115 samples) showed significantly higher concentrations of antibodies against SARS-CoV-2 and differed from outpatient cases (n=65) by higher age, higher disease severity scores and earlier follow up blood sampling. Sensitivity of the two IgG assays was comparable in hospitalized patients tested ≥ 14 days (EI-assay: 88%, CI95% 67.6-99.9; VT-assay: 96%, CI95% 77.7-99.8). In outpatient COVID-19 cases sensitivity was significantly lower in the VT-assay (86.2%, CI95% 74.8-93.1) compared with the EI-assay (98.5%, CI95% 90.6-99.9). Assays for IgA and IgM demonstrated a lack of specificity or sensitivity.
CONCLUSIONS: Our results indicate that SARS-CoV-2 serological assays may need to be optimized to produce reliable results in outpatient COVID-19 cases who are low or even asymptomatic. Assays for IgA and IgM have limited diagnostic performance and do not prove an additional value for population-based screening approaches.

PMID: 33159952 [PubMed – as supplied by publisher]

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