Polyautoimmunity Reflecting Immune Dysregulation in Common Variable Immunodeficiency.

Background

Common variable immunodeficiency (CVID) is the most frequent symptomatic inborn error of immunity (IEI) in adulthood. Other than recurrent infections, CVID may present with non-infectious complications such as enteropathy, lymphoproliferation, malignancy, and autoimmune diseases. Patients could have a single autoimmune disease (monoautoimmunity) or two or more autoimmune diseases (overt polyautoimmunity). "Latent polyautoimmunity" corresponds to the presence of autoantibodies without a clinically evident autoimmune disease.

Methods

The aim of this retrospective study was to describe autoimmunity and polyautoimmunity in a population of 81 CVID adult patients, enrolled from January 2008 to July 2022 (mean follow-up: 8.5 years).

Results

We documented at least one autoimmune disorder in 40 patients (49.4%). Moreover, 15 subjects (37.5% of patients with autoimmunity and 18.5% of all CVID population) presented polyautoimmunity. Despite the humoral immune deficiency, we detected different autoantibodies in CVID patients with or without a concomitant autoimmune disease. In both groups with monoautoimmunity and polyautoimmunity, cytopenias were the most common manifestation. Conversely, enteropathy was recorded only in patients with polyautoimmunity (27%, p = 0.006). Patients with polyautoimmunity showed a significantly lower mean age at diagnosis (-12 years, p = 0.018) compared to those with monoautoimmunity. We documented a higher frequency of autoimmunity in CVID patients who had increased diagnostic (+5.6 years) and therapeutic (+7.2 years) delay (p = 0.093 and 0.054, respectively).

Conclusions

Polyautoimmunity is a frequent condition in patients affected by CVID. An early start of Ig replacement therapy could help prevent autoimmune complications.