The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives

Abstract

T he etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in depth, there are only a few reports on milder primary antibody deficiencies such as idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 patients with common variable immunodeficiency, 23 with idiopathic primary hypogammaglobulinemia and 21 with IgG subclass deficiency, as well as in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three groups of patients showed decreased memory B-and naïve T-cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T-cell frequency and expression of inducible T-cell costimulator and chemokine receptors were only significantly altered in patients with common variable immunodeficiency. Asymptomatic firstdegree family members of patients demonstrated similar, albeit intermediate, alterations in naïve and memory B-and T-cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B-cell composition. Furthermore, asymptomatic relatives showed decreased levels of CD4 + recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives than in healthy controls. We conclude that, in our cohort, the immunophenotypic landscape of primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients were found to have an intermediate phenotype for peripheral Band T-cell subsets.

What Are the Characteristics of the Upper Airway in Patients With Craniofacial Microsomia?

“…This contrasts with previous flow cytometric studies that detected Bcell defects in only 6% to 86% of patients with PADs, namely 77% to 86% in patients with CVID, 14,15,18,20,23,40,41 6% to 25% in patients with IgAdef, 19,35 and 30% in patients with selective IgG subclass deficiency (with or without IgAdef). 41 This high (Fig 3, A; light green for patients with IgAdef, intermediate green for patients with IgG/Adef, and dark green for patients with CVID); (2) their corresponding ESID IgAdef diagnosis (Fig 3, B), including IgAdef cases that fulfilled (black) or not (gray) the ESID criteria for IgAdef; and (3) CVID EUROclass classification subgroup (Fig 3, C), smB 1 CD21 normal , smB 1 CD21 lo , smB 2 CD21 normal , smB 2 CD21 lo , and B2 cells from lighter to darker violet. The here-defined PAD-1 to PAD-5 (Fig 3, A), IgAdef-1 and IgAdef-2 (Fig 3, B), and CVID-1 to CVID-6 (Fig 3, C) clusters identified by using the K-means algorithm, as well as the main characteristics of these groups, are depicted at the right side of each heat map.…”

Online yoga in myeloproliferative neoplasm patients: results of a randomized pilot trial to inform future research

“…Furthermore, advertising the study as a “symptom management study” as opposed to a “yoga study” could further help to reduce an entirely self-selected study sample interested in yoga or already physically active.Strategies for including patients with a broader range of depressive symptoms - A total of 37% of those ineligible for this study were ineligible due to reporting moderate-severe depression (according to PHQ-9 score ≥ 15). However, yoga may be beneficial for patients with moderate-severe depressive symptoms as yoga has been shown to improve depressive symptoms in other cancer patient populations [10–13] and cross-sectional work has identified a negative association between self-report yoga participation and reduced depressive symptoms in MPN patients [15]. Future studies should include a clinical psychologist/psychiatrist to oversee participants reporting moderate-severe depression (i.e., including them in the study population).Identify potential confounding factors - Medications/treatments that may affect symptoms were not recorded throughout the study by participants, however, it is possible that study participants started or stopped taking medications, or received new treatments (unbalanced between groups) during their participation in the study.…”

“…Strategies for including patients with a broader range of depressive symptoms - A total of 37% of those ineligible for this study were ineligible due to reporting moderate-severe depression (according to PHQ-9 score ≥ 15). However, yoga may be beneficial for patients with moderate-severe depressive symptoms as yoga has been shown to improve depressive symptoms in other cancer patient populations [10–13] and cross-sectional work has identified a negative association between self-report yoga participation and reduced depressive symptoms in MPN patients [15]. Future studies should include a clinical psychologist/psychiatrist to oversee participants reporting moderate-severe depression (i.e., including them in the study population).…”

“…In a survey of over 850 MPN patients, cross-sectional data demonstrated that 26% of MPN patients ( n = 220) reported participating in yoga and that self-reported yoga participation was significantly associated with an improved total symptom burden ( p = 0.02), reduced depressive symptoms ( p = 0.001), and improved quality of life (p = 0.02) [15]. Furthermore, a recent study by Huberty et al [16] explored a 12-week online yoga (OLY) intervention in MPN patients ( n = 38) and found yoga to be feasible (i.e., acceptable & practical), with average weekly self-reported yoga participation of ~ 50 min/week (60 min/week was prescribed) and a high rate of satisfaction (i.e., 68% satisfied or very satisfied and 75% found it helpful for coping with symptoms).…”

A novel IKAROS haploinsufficiency kindred with unexpectedly late and variable B-cell maturation defects

“…Peripheral blood B- and T-cell subsets were evaluated in the IKZF1 mutation carriers (subjects I:2, II:3 and II:4) and age-matched healthy control subjects, as previously described E3. In brief, cryopreserved PBMCs were stained with Fixable Viability Dye 506 (eBioscience, San Diego, Calif) and fluorescently labeled mAbs under saturation conditions.…”