TREC and KREC Levels as a Predictors of Lymphocyte Subpopulations Measured by Flow Cytometry

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases, or malignancies. Early detection of other PID remains a challenge, particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappadeleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice. This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins. We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8, and CD19), IgA, IgM, and IgG analysis. A total of 839 samples were analyzed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70–0.76) for CD3, 0.74 (95% CI 0.71–0.77) for CD4 and 0.67 (95% CI 0.63–0.70) for CD8, respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69–0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r = 0.55, p < 0.01) and KREC with CD19 (r = 0.56, p < 0.01). In this study, promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis

TREC and KREC Levels as a Predictors of Lymphocyte Subpopulations Measured by Flow Cytometry

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases, or malignancies. Early detection of other PID remains a challenge, particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice. This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins. We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8, and CD19), IgA, IgM, and IgG analysis. A total of 839 samples were analyzed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70–0.76) for CD3, 0.74 (95% CI 0.71–0.77) for CD4 and 0.67 (95% CI 0.63–0.70) for CD8, respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69–0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r = 0.55, p &lt; 0.01) and KREC with CD19 (r = 0.56, p &lt; 0.01). In this study, promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis

Health-Related Quality of Life in Children and Adults with Primary Immunodeficiencies: A Systematic Review and Meta-analysis

BACKGROUND: Primary immunodeficiency disorders (PID) is a group of diseases that has been found to have an adverse impact on Quality of Life (QoL) and health related quality of life (HRQL). OBJECTIVE: To systematically assess available evidence on PID patients HRQL. METHODS: We performed a literature search of all studies reporting HRQL assessments in patients with PID published in English from inception to 11 April 2017 using MEDLINE and EMBASE. RESULTS: Out of 1699 articles, 37 met the inclusion criteria. HRQL was assessed by using a variety of generic instruments. CHQ-PF50 and SF-36 were the most frequently used (for children and adults, respectively). No PID-specific HRQL instruments were used for children. HRQL is significantly lower in PID adults (mean score difference -24.46, 95%CI, -34.57; -14.34) and children (-10.06, -12.95; -7.17) compared to the reference population and lower than in patients with other chronic conditions. There is a general agreement between child- and parent-reported data, although parents report child school-related HRQL as more impaired than children (6.19, 0.38; 11.99). Most studies were of low to moderate quality and had methodological limitations. CONCLUSION: Available evidence suggests that PID patients have a lower HRQL than healthy individuals and patients with other chronic conditions, including diabetes mellitus and juvenile idiopathic arthritis. No disease-specific instruments are available for children and few options are available for adults. This finding highlights the need for developing PID-specific instruments which would allow for a more sensitive evaluation of PID impact on patient health and psychological wellbeing, school/work and social activities

Statistical approaches in the studies assessing associations between human milk immune composition and allergic diseases: A scoping review

A growing number of studies are focusing on the associations between human milk (HM) immunological composition and allergic diseases. This scoping review aims to identify statistical methods applied in the field and highlight pitfalls and unmet needs. A comprehensive literature search in MEDLINE and Embase retrieved 13,607 unique records. Following title/abstract screening, 29 studies met the selection criteria and were included in this review. We found that definitions of colostrum and mature milk varied across the studies. A total of 17 out of 29 (59%) studies collected samples longitudinally, but only 12% of these used serial (longitudinal) analyses. Multivariable analysis was used in 45% of the studies, but statistical approaches to modelling varied largely across the studies. Types of variables included as potential confounding factors differed considerably between models. Discrimination analysis was absent from all studies and only a single study reported classification measures. Outcomes of this scoping review highlight lack of standardization, both in data collection and handling, which remains one of the main challenges in the field. Improved standardization could be obtained by a consensus group of researchers and clinicians that could recommend appropriate methods to be applied in future prospective studies, as well as already existing datasets