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Viruses. 2021 Mar 12;13(3):470. doi: 10.3390/v13030470.

ABSTRACT

Although the antibody response induced by primary vaccination with Fel-O-Vax^® FIV (three doses, 2-4 weeks apart) is well described, the antibody response induced by annual vaccination with Fel-O-Vax^® FIV (single dose every 12 months after primary vaccination) and how it compares to the primary antibody response has not been studied. Residual blood samples from a primary FIV vaccination study (n = 11), and blood samples from cats given an annual FIV vaccination (n = 10), were utilized. Samples from all 21 cats were tested with a commercially available PCR assay (FIV RealPCR^TM), an anti-p24 microsphere immunoassay (MIA), an anti-FIV transmembrane (TM; gp40) peptide ELISA, and a range of commercially available point-of-care (PoC) FIV antibody kits. PCR testing confirmed all 21 cats to be FIV-uninfected for the duration of this study. Results from MIA and ELISA testing showed that both vaccination regimes induced significant antibody responses against p24 and gp40, and both anti-p24 and anti-gp40 antibodies were variably present 12 months after FIV vaccination. The magnitude of the antibody response against both p24 and gp40 was significantly higher in the primary FIV vaccination group than in the annual FIV vaccination group. The differences in prime versus recall post-vaccinal antibody levels correlated with FIV PoC kit performance. Two FIV PoC kits that detect antibodies against gp40, namely Witness^® and Anigen Rapid^®, showed 100% specificity in cats recently administered an annual FIV vaccination, demonstrating that they can be used to accurately distinguish vaccination and infection in annually vaccinated cats. A third FIV PoC kit, SNAP^® Combo, had 0% specificity in annually FIV-vaccinated cats, and should not be used in any cat with a possible history of FIV vaccination. This study outlines the antibody response to inactivated Fel-O-Vax^® FIV whole-virus vaccine, and demonstrates how best to diagnose FIV infection in jurisdictions where FIV vaccination is practiced.

PMID:33809232 | DOI:10.3390/v13030470

Int J Mol Sci. 2021 Mar 4;22(5):2551. doi: 10.3390/ijms22052551.

ABSTRACT

Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups-a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease.

PMID:33806322 | DOI:10.3390/ijms22052551

Cell Mol Immunol. 2021 Apr 1. doi: 10.1038/s41423-020-00626-z. Online ahead of print.

ABSTRACT

In addition to susceptibility to infections, conventional primary immunodeficiency disorders (PIDs) and inborn errors of immunity (IEI) can cause immune dysregulation, manifesting as lymphoproliferative and/or autoimmune disease. Autoimmunity can be the prominent phenotype of PIDs and commonly includes cytopenias and rheumatological diseases, such as arthritis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS). Recent advances in understanding the genetic basis of systemic autoimmune diseases and PIDs suggest an at least partially shared genetic background and therefore common pathogenic mechanisms. Here, we explore the interconnected pathogenic pathways of autoimmunity and primary immunodeficiency, highlighting the mechanisms breaking the different layers of immune tolerance to self-antigens in selected IEI.

PMID:33795850 | DOI:10.1038/s41423-020-00626-z

Klin Lab Diagn. 2021 Mar 30;66(3):160-165. doi: 10.51620/0869-2084-2021-66-3-160-165.

ABSTRACT

Common variable immunodeficiency (CVID) is a variant of primary immunodeficiency in which inhibition of antibody production is formed due to disorders of intercellular interaction affecting cellular elements of both innate and adaptive immune responses. A feature of CVID is the late start and variability of clinical minifestation. These arguments determine the purpose of the study: to identify the dynamics of changes in the cellular parameters of the adaptive and innate immune response depending on the duration and severity of the infectious manifestation of CVID. In this regard, a retrospective analysis of medical histories and dynamic observation of fifteen patients with CVID were carried out. Selection of specific parameters of cellular indices of factors of innate resistance and adaptive immunity was carried out on the basis of systemic-functional approach of immunodiagnostics. It is shown that in patients with CVID -mediated hypogammaglobulinemia and infectious phenotype of clinical manifestation, enhancement of quantitative and functional potentials of T-link effector cells of adaptive immunity is recorded against the background of reduction of number of regulatory T-helpers. With a more severe clinical course of the disease, the number of CD3+HLA DR + limphocytes is lower than with a more favorable version, there is a tendency to decrease the number of these cells, as well as the number of peripheral Treg with an increase in the length of the disease. Cellular components of innate immunity are characterized by a decrease in neutrophil activity, inhibition of antigen-presenting monocyte activity, the number and cytotoxicity of natural killers. At the same time, the tendency to decrease the cytolytic potential of NK with an increase in the length of illness and statistically significant differences depending on the severity of the manifestation of the infectious phenotype of CVID was recorded. The obtained results determine the importance of evaluating the cellular link of the immune system in patients with CVID, including as a prognostic criterion for the severity of the course.

PMID:33793115 | DOI:10.51620/0869-2084-2021-66-3-160-165

Clin Exp Immunol. 2021 Mar 31. doi: 10.1111/cei.13600. Online ahead of print.

ABSTRACT

CTLA-4 haploinsufficiency (CHAI) and LRBA deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunologic, and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science, and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and Western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (p<0.001) and in LATAIE, consanguineous parents (p<0.001) were more common. In CHAI patients the rates of granulomas (p<0.001), malignancies (p=0.001), atopy (p=0.001), cutaneous disorders (p<0.001), and neurologic (p=0.002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (p=0.002), pneumonia (p=0.006), ear-nose-throat disorders (p<0.001), organomegaly (p=0.023), autoimmune enteropathy (p=0.038), and growth failure (p<0.001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD19+ B cells (14.0% vs. 38.4%, p<0.001), natural killer (NK) cells (21% vs. 41.1%, p<0.001), IgG (46.9% vs. 41.1%, p=0.291), and IgA (54.5% vs. 44.7%, p=0.076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biologic immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.

PMID:33788257 | DOI:10.1111/cei.13600

Medicine (Baltimore). 2021 Apr 2;100(13):e20866. doi: 10.1097/MD.0000000000020866.

ABSTRACT

INTRODUCTION: DOCK8 deficiency is a primary immunodeficiency characterized by recurrent infections, severe allergic disease, and autoimmunity. Here, we report a patient with DOCK8 deficiency that was initially presented as systemic lupus erythematosus (SLE) without recurrent infections and treated with hematopoietic stem cell transplantation (HSCT).

PATIENT CONCERNS: A 16-month-old boy with a previous history of eczema developed high fever and hand and foot swelling. Over time, multiple purpura, oral ulcers, and oliguria developed with a persistent fever. His laboratory findings showed anemia, thrombocytopenia, and coagulopathy with a high level of C-reactive protein (CRP). No definite pathogens were identified. The complement fractions C3, C4, and CH50 were low. Autoantibodies including antinuclear antibody (ANA) and anti-ds DNA antibody were positive. He definitively satisfied the 2015 ACR/SLICC revised criteria for the diagnosis of SLE (7 points out of 16); therefore, he was treated with a steroid. Lupus nephritis was confirmed by renal biopsy later. Considering the early-onset SLE, partial exome sequencing was performed.

DIAGNOSIS: One heterozygous missense variant, c.5536A>G (p.Lys1846Glu), which was inherited from his father, and heterozygous deletion of exon 1 to 8 inherited from his mother were found. Through the results of the genetic testing, the patient was confirmed to have DOCK8 deficiency.

INTERVENTIONS: At the age of 28 months, he received haploidentical HSCT from his mother as a donor.

OUTCOMES: Laboratory findings including complement fractions C3, C4, CH50, anti-ds DNA antibody, and the ANA became normal after HSCT. Currently, at 12 months post-HSCT, he is doing well, without any autoimmune features or infections.

CONCLUSIONS: DOCK8 deficiency can be presented as autoimmune disease such as SLE. Encountering a child diagnosed with SLE at a very young age, pediatricians should consider immunodeficiency syndrome including DOCK8 deficiency.

PMID:33787566 | DOI:10.1097/MD.0000000000020866

Immunol Res. 2021 Mar 30. doi: 10.1007/s12026-021-09186-4. Online ahead of print.

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves several organ systems. Although B cells play a key role in SLE pathogenesis, the mechanisms behind B cell dysregulation in SLE development remained controversial. Finding the modules containing highly co-expressed genes in B cells could explain biological pathways involved in the pathogenesis of SLE, which may further support the reasons for the altered function of B cells in SLE disease. A total of three microarray gene expression datasets were downloaded from Gene Expression Omnibus. SLE samples were prepared from the purified B lymphocyte cells of the patients who have not received immunosuppressive drugs as well as high dose immunocytotoxic therapies or steroids. A weighted gene co-expression network was then constructed to find the relevant modules implicated in the SLE progression. Among 17 identified modules, 3 modules were selected through mapping to STRING and finding the ones that had highly connection at the protein level. These modules clearly indicate the involvement of several pathways in the pathogenesis of SLE including viral infection, adaptive immune response, and innate immune response in B lymphocytes. The WGCN analysis further revealed the co-expressed genes involved in both innate and adaptive immune systems. Mix infections and primary immunodeficiency might also dysregulate B lymphocytes, which may facilitate SLE development. As such, identifying novel biomarkers and pathways in lupus would be of importance.

PMID:33786699 | DOI:10.1007/s12026-021-09186-4

Clin Exp Pediatr. 2021 Mar 25. doi: 10.3345/cep.2020.01270. Online ahead of print.

ABSTRACT

Population screening of newborns is an extremely important and informative diagnostic approach that allows early identification of babies who are predisposed to the development of a number of serious diseases. Some of these diseases are known and have effective treatment methods. Neonatal screening enables the early diagnosis and subsequent timely initiation of therapy. This helps to prevent serious complications and reduce the percentage of disability and deaths among newborns and young children. Primary immunodeficiency diseases and primary immunodeficiency syndrome (PIDS) are a heterogeneous group of diseases and conditions based on impaired immune system function associated with developmental defects and characterized by various combinations of recurrent infections, development of autoimmune and lymphoproliferative syndromes (genetic defects in apoptosis, gene mutation Fas receptor or ligand), granulomatous process, and malignant neoplasms. Most of these diseases manifest in infancy and lead to serious illness, disability, and high mortality rates. Until recently, it was impossible to identify children with PIDS before the onset of the first clinical symptoms, which are usually accompanied by complications in the form of severe co-infections of a viral-bacterial-fungal etiology. Modern advances in medical laboratory technology have allowed the identification of children with severe PIDS, manifested by T- and/or B-cell lymphopenia and other disorders of the immune system. This review discusses the main existing strategies and directions used in PIDS screening programs for newborns, including approaches to screening based on excision of T-cell receptors and kappa-recombination excision circles, as well as the potential role and place of next-generation sequencing technology to increase the diagnostic accuracy of these diseases.

PMID:33781055 | DOI:10.3345/cep.2020.01270

Front Med (Lausanne). 2021 Mar 12;8:665475. doi: 10.3389/fmed.2021.665475. eCollection 2021.

ABSTRACT

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased frequency of infections and neoplasms. However, if the observed immunity dysregulation is secondary and pharmaceutically induced or there is a pre-existing, primary immunodeficiency that shares common pathogenetic pathways with SLE’s autoimmunity is not always clear. Herein, we present the case of a 39-year-old woman, that reached ESKD due to lupus nephritis. After an upper respiratory cytomegalovirus (CMV) infection and concomitant CMV reactivations the investigation revealed significant immunodeficiency. Not long after the initiation of intravenous immunoglobulin (IVIG) administration, patient received a cadaveric kidney transplant. IVIG was continued along with standard immunosuppression so that both recurrent infections and allograft rejection are avoided. Patient is closely monitored, and her post-transplant course is remarkably satisfying so far. ESKD patients with immunodeficiency syndromes should not be excluded by definition from kidney transplantation.

PMID:33777986 | PMC:PMC7994764 | DOI:10.3389/fmed.2021.665475

Respir Med Case Rep. 2021;33:101397. doi: 10.1016/j.rmcr.2021.101397. Epub 2021 Mar 24.

ABSTRACT

BACKGROUND: COVID-19 is a potentially critical infectious disease. Inflammatory response and disease severity may vary according to immune system status. The aim of this case series is to investigate different presentation of COVID-19 in immunocompromised patients.

METHODS: this is a single centre case series about 17 immunocompromised patients admitted to our respiratory department during the recent COVID-19 pandemic. White blood cell count, C reactive protein, interleukin 6, lymphocytic subpopulation count (CD4⁺, CD8⁺, CD20⁺) and immunoglobulin count (IgG, IgM, IgA) were measured at hospitalization.

RESULTS: the most common causes of immunosuppression observed in our severe COVID-19 population are hematological malignancies, immunosuppressant drugs for transplant, primary immunodeficiency and inflammatory bowel disease. Onset symptoms were fever (88%), cough (53%), dyspnoea (24%), asthenia (35%), anosmia and/or ageusia (17%), expectoration (12%). Compared to benign conditions, patients with malignancies show a lower lymphocytic count (490 vs 1100 cells/uL) and higher interleukin 6 (33 vs 13 pg/mL).

CONCLUSIONS: immunocompromised patients are at risk of adverse outcome from COVID-19. Hematological malignancies and anti-CD20 therapies induce a high risk. Primary immunodeficiency and classical immunosuppressant such as calcineurin inhibitors and antimetabolites share an intermediate risk.

PMID:33777690 | PMC:PMC7987579 | DOI:10.1016/j.rmcr.2021.101397