Health Related Quality of Life in Common Variable Immunodeficiency Diseases evaluated by different tools were mainly used to compare different schedules of immunoglobulins administration in cross-sectional or short-term longitudinal studies. We assessed the health related quality of life and psychological status of CVID patients in a longitudinal study over a six years period by a generic, not disease-specific instrument (SF-36), and the risk of depression/anxiety by GHQ-12. At baseline, 96 patients were enrolled. After one year, a second assessment on 92 patients and after six years a third assessment on 66 patients were performed. Eighteen patients died during the study time. Health Related Quality of Life was low, with mental health scales less affected than physical scales. Worsening in SF-36 scales between the first and the third assessment was found for the physical functioning, body pain, general health, social functioning, role-emotional, scales. General Health scale showed a worse score in comparison to patients with other chronic diseases. We showed by GHQ-12 assessment that about one third of patients were at risk of anxiety/depression at all observation times, a figure that reached two third of patients only considering the group of females. Over the 6-years, 11/66 patients worsened their general health condition, passing from “GHQ-negative” to “GHQ-positive”, and worsened in SF-36 scales. A decrement of 1-point in each of physical functioning, vitality, social functioning and mental health scales increased the risk of developing anxiety/depression from 3 to 5 per cent. A negative variation of physical functioning increased the risk of psychological distress. In a survival analysis with dichotomized variables, physical functioning scores < 50 were associated with a RR of 4.4 and social functioning scores <37.5 with a RR of 10.0. In our study, the clinical condition and not the different treatment strategies with immunoglobulins had a major role on deter

The 2017 International Union of Immunological Societies (IUIS) classification recognizes 3 hyper‐IgE syndromes (HIES), including the prototypic Job's syndrome (autosomal dominant STAT3‐loss of function) and autosomal recessive PGM3 and SPINK5 syndromes. Early diagnosis of PID can direct life‐saving or transformational interventions; however, it remains challenging owing to the rarity of these conditions. This can result in diagnostic delay and worsen prognosis. Within increasing access to “clinical‐exome” testing, clinicians need to be aware of the implication and rationale for genetic testing, including the benefits and limitations of current therapies. Extreme elevation of serum IgE has been associated with a growing number of PID syndromes including the novel CARD11 and ZNF341 deficiencies. Variable elevations in IgE are associated with defects in innate, humoral, cellular and combined immunodeficiency syndromes. Barrier compromise can closely phenocopy these conditions. The aim of this article was to update readers on recent developments at this important interface between allergy and immunodeficiency, highlighting key clinical scenarios which should draw attention to possible immunodeficiency associated with extreme elevation of IgE, and outline initial laboratory assessment and management.

Background: Patients with primary antibody deficiencies are at risk in the current COVID-19 pandemic due to their impaired response to infection and vaccination. Specifically, patients with common variable immunodeficiency (CVID) generated poor spike-specific antibody and T cell responses after immunization. Methods: Thirty-four CVID convalescent patients after SARS-CoV-2 infection, 38 CVID patients immunized with two doses of the BNT162b2 vaccine, and 20 SARS-CoV-2 CVID convalescents later and immunized with BNT162b2 were analyzed for the anti-spike IgG production and the generation of spike-specific memory B cells and T cells. Results: Spike-specific IgG was induced more frequently after infection than after vaccination (82% vs. 34%). The antibody response was boosted in convalescents by vaccination. Although immunized patients generated atypical memory B cells possibly by extra-follicular or incomplete germinal center reactions, convalescents responded to infection by generating spike-specific memory B cells that were improved by the subsequent immunization. Poor spike-specific T cell responses were measured independently from the immunological challenge. Conclusions: SARS-CoV-2 infection primed a more efficient classical memory B cell response, whereas the BNT162b2 vaccine induced non-canonical B cell responses in CVID. Natural infection responses were boosted by subsequent immunization, suggesting the possibility to further stimulate the immune response by additional vaccine doses in CVID.

Generic health status quality of life (QoL) instruments have been used in patients with common variable immune deficiency (CVID). However, by their nature, these tools may over- or underestimate the impact of diseases on an individual's QoL. The objective of this study was to develop and validate a questionnaire to measure specific-health-related QoL for adults with CVID (CVID_QoL). The 32-item content of the CVID_QoL questionnaire was developed using focus groups and individual patient interviews. Validation studies included 118 adults with CVID who completed Short Form-36, Saint George Respiratory Questionnaire, General Health Questionnaire-12, and EuroQol-5D questionnaire in a single session. Principal component and factor analysis solutions identified 3 scores to be similar in number and content for each solution. Validation of 3 factor scores was performed by construct validity. Reproducibility, reliability, convergent validity, and discriminant validity were evaluated. Matrices consisting of correlations between the 32 items in the CVID_QOL were calculated. Factor analysis identified 3 dimensions: emotional functioning (EF), relational functioning (RF), and gastrointestinal and skin symptoms (GSS). The instrument had good internal consistency (Cronbach's alpha, min. 0.74 for GSS, max. 0.84 for RF, n = 118) and high reproducibility (intraclass correlation coefficient, min. 0.79 for RF, max 0.90 for EF, n = 27). EF and RF scores showed good convergent validity correlating with conceptually similar dimensions of other study scales. Acute and relapsing infections had a significant impact on EF and RF. This study provides evidence of the reliability and construct validity of the CVID_QoL to identify QoL issues in patients with CVID that may not be addressed by generic instruments.

Background and Aim. Portal hypertension has been reported in association with acquired and primary immune deficiencies without a comprehensive description of associated spleno-portal axis abnormalities. Pathological mechanisms are poorly defined.Methods. Observational, single centre study with the aim of assessing the prevalence of spleno-portal axis abnormalities in an unselected cohort of 123 patients with primary antibody deficiencies and without known causes of liver diseases regularly followed up for a mean time of 18 ± 14 years. A cumulative period of 1867 patients-year was analysed. Clinical and immunological data, abdominal ultrasounds, CT scans, and endoscopy features were included in the analysis.Results. Twenty-five percent of patients with primary antibody deficiencies had signs of portal vein enlargement but only 4% of them had portal hypertension, with portal systemic collaterals. Liver biopsies showed liver sinusoids congestive dilatation, endothelization, and micronodularity fulfilling the criteria for noncirrhotic portal hypertension. Patients with portal vein enlargement had severe clinical and immunological phenotypes.Conclusions. In primary antibody deficient patients, infections, inflammations, splenomegaly, increased blood venous flow, and lymphocyte abnormalities contribute to establishment of liver damage possibly leading to noncirrhotic portal hypertension. Patients with primary antibody deficiency should be considered a good model to give insight into the pathological mechanisms underlying noncirrhotic portal hypertension.