Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry

Abstract

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans’ syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients.

An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression

“…Even today, CVID diagnosis is based on exclusion criteria without any ndings considered pathognomonic of the disease. Timely diagnosis and prompt and effective treatment are extremely important for patients, reducing morbidity and mortality 19,20 . By comparing several classi ers, we were able to determine the optimal model for the data.…”

Activated PI3Kδ syndrome – reviewing challenges in diagnosis and treatment

“…Unfortunately, these do not include signs like autoimmunity or lymphoproliferation. Expertise in diagnosing IEIs is mostly confined to physicians specialized in managing primary immunodeficiencies, and diagnosing immune-related disorders may take up to ten years, as is the case with APDS ( 12 , 14 , 65 , 66 ), the discovery of the causative gene variants underlying APDS has helped shorten this delay. Given the sparsity and geographical distribution of clinical immunologists, there is a high probability of patients not being directly referred to a specialist.…”

Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

“…Polyclonal lymphoid infiltration is an expression of the immune dysregulation in CVID, presenting in various forms: persistent lymphadenopathies, non-infectious enteropathy, and splenomegaly are rather frequent; less commonly, liver infiltration with hepatomegaly, liver nodules, and lymphoid interstitial pneumonia [101]. As with the other non-infectious complications, lymphocytic infiltration is unaffected by immunoglobulin replacement therapy.…”

“…Splenomegaly can occur in adults and children; patients with hypersplenism and autoimmune thrombocythemia or autoimmune hemolytic anemia which previously required splenectomy can be treated with immunosuppressive drugs or antimetabolites [101,102].…”

“…Immunosuppressants such as azathioprine/mycophenolate/cyclophosphamide [197] may be moderately effective as second-line drugs and the risk-benefit ratio needs to be addressed with regard to infectious complications [86]. Severe refractory ITP/AIHA may be treated with immunosuppressive drugs or antimetabolites [101,102] and splenectomy is burdened by a high risk of sepsis. Immunoglobulin replacement therapy can be employed in SIgAD with particular caution; either administered by the subcutaneous route, or using IgA-depleted blood products.…”