The prevalence, clinical relevance and origin of autoantibodies in
patients with Common variable immunodeficiency on regular immunoglobulin
replacement therapy
Abstract
Background: Common variable immunodeficiency (CVID) is an inborn error
of immunity characterized by disturbed immunoglobulin production.
Despite of the terrain with severe antibody deficiency,
autoantibody-mediated autoimmune phenomena belong to the most frequent
autoimmune manifestation. However, many unresolved issues such as
prevalence, clinical relevance and origin of autoantibodies detected in
CVID patients receiving immunoglobulin replacement therapy (IRT) make
the diagnostics of autoimmune complications difficult. Methods: A
prospective observational study evaluating the spectrum of 38 different
autoantibodies in 38 CVID patients receiving IRT, and in the
immunoglobulin solutions used for IRT. Results: The study reveals a high
prevalence of anti-GAD (55.3%) and anti-TPO (68.4%) autoantibodes in
the cohort of 38 CVID patients on regular IRT. However, the titers of
anti-GAD (3.22 vs. 22 kU/L, p≤0.0001) and anti-TPO (109.7 vs. 713 kU/L,
p≤0.0001) were significantly lower compared to the newly diagnosed T1D
and AIT patients. Moreover, none of the CVID patients with detectable
antibodies manifested with T1D and only three patients became suspected
of having AIT. A high quantity of anti-GAD (3.24-24.48 kU/L) and
anti-TPO (123.6-156.55 kU/L) autoantibodies was found in immunoglobulin
solutions for IRT. Conclusions: The study finds a very high prevalence
of anti-GAD and anti-TPO autoantibodies in CVID patients receiving
regular IRT. Nevertheless, the presence of anti-GAD and anti-TPO is not
associated with the manifestation of the respective autoimmune disease.
As the high titers of both anti-GAD and anti-TPO were also found in the
therapeutics used for IRT, we suggest that the therapeutic
immunoglobulins are the source of this false positivity.