Common variable immunodeficiency (CVID) is a diverse group of primary immune disorders characterized primarily by low antibody levels, leading to frequent infections as well as serious non-infectious complications like organ damage, autoimmunity, and even cancer.
These issues can significantly shorten life expectancy, but until recently, clinicians lacked reliable ways to predict which patients were at highest risk.
These issues can significantly shorten life expectancy, but until recently, clinicians lacked reliable ways to predict which patients were at highest risk.
A large multicenter study of 209 CVID patients (compared against healthy controls) has identified key biomarkers that strongly correlate with disease course and survival. Researchers focused on serum immunoglobulins, T-cell subsets (especially naive CD4+ T cells), B-cell/plasma cell defects, and natural killer (NK) cells.
Infectious complications, particularly recurrent respiratory infections, were closely tied to low serum immunoglobulins — especially IgA.
Non-infectious complications (such as splenomegaly, lymphadenopathy, interstitial lung disease, cytopenias, enteropathy, liver disease, and lymphoma) were more strongly linked to specific immune cell defects:
Late-onset combined immunodeficiency (LOCID) — marked by severe reduction in naive CD4+ T cells — emerged as a major risk factor for many of these complications.
A pronounced defect in classical CD27+ memory B cells (27MBC−), often accompanied by lower NK cells and IgM, was associated with higher risks of enteropathy and (together with LOCID and low IgA) liver disease.
Most importantly for patient prognosis:
Lower serum IgG, presence of LOCID, and especially the absence of CD27+ memory B cells were the strongest predictors of shorter survival and earlier death.
Genetic risk alleles associated with CVID did not independently predict outcomes in this cohort.
These biomarker profiles offer clinicians a practical toolset to stratify risk, guide closer monitoring, and tailor management for CVID patients. By identifying those at greatest risk of severe complications early, this approach could help improve long-term outcomes and quality of life in this challenging condition.
References:
https://www.jacionline.org/article/S0091-6749(25)01079-6/fulltext