A Comparison of Clinical and Immunologic Phenotypes in Familial and Sporadic Forms of Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency disease, and its prevalence varies significantly among different population. Minority of CVID patients present a familial aggregation suggesting a higher probability of heritable genetic defects. A total of 235 registered CVID patients were evaluated in this cohort study. Familial and sporadic patients were stratified, and demographic information, clinical records, laboratory and molecular data were compared among these two groups of patients. Multiple cases were identified in 12 families (30 patients) and sporadic presentation in 120 cases. The rate of parental consanguinity (83.3%) and clinical presentation of lymphoid malignancy (20.7%) were predominant in familial CVID patients, whereas significantly increased recurrent upper respiratory infections were recorded in sporadic patients (0.3 infections per year). Probands of familial group were presented with a higher severity score resulting in a profound mortality rate (41.7% after 30-year follow-up) comparing to the non-proband CVID patients in the same families with a lowered diagnostic delay. Familial CVID patients had a specific signature in clinical presentation and immunologic profile, and a high consanguinity in this group of patients suggests a Mendelian trait with an autosomal recessive inheritance pattern. Diagnosis of an index patient within a multiple case families significantly improves the diagnostic process and outcomes of the yet asymptomatic patients.

Primary antibody deficiencies in Turkey: molecular and clinical aspects

“…Although more than thirty genes have been linked to CVID, the genetic basis remains unclear in most cases, with only 2-10% of the patients having known monogenic disorders. Positive family history and parental consanguinity rates were changed according to countries; with a range20-80% of all CVID cases [12,13].…”

Rheumatologic complications in a cohort of 227 patients with common variable immunodeficiency

“…Common variable immunodeficiency (CVID) is the most frequent symptomatic type of human primary immunodeficiency diseases (PID) . CVID constitutes a large heterogeneous group of patients with antibody deficiencies, and a prevalence of 1:50 000‐1:20 000 has been estimated for the disease . However, due to variable presentations of the disease, lack of physician awareness and misdiagnoses in patients with CVID with atypical clinical manifestations, the prevalence of CVID in our country [registered in Iranian PID Registry (IPIDR)] is underestimated (~1:20 000).…”

“…However, due to variable presentations of the disease, lack of physician awareness and misdiagnoses in patients with CVID with atypical clinical manifestations, the prevalence of CVID in our country [registered in Iranian PID Registry (IPIDR)] is underestimated (~1:20 000). CVID is characterized by low levels of serum immunoglobulin (Ig), reduced specific antibody response to polysaccharide and/or protein antigens and increased episodes of infections during childhood or young adulthood . Immune dysregulation in patients with CVID results in lymphoproliferation, granulomatous disease, malignancy, allergy and a higher prevalence of inflammatory and autoimmune conditions .…”

Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients

“…Parental consanguinity and the autosomal recessive mode of inheritance are risk factors for primary immunodeficiency disorders. 9 , 12 , 13 In Rivoisy et al’s 14 study, CVID patients who had consanguineous parents had more severe complications like splenomegaly, granulomatous disease, and bronchiectasis. In our study, parental consanguinity and positive family history rates were 19.1% and 11.8%, respectively.…”