Negativity for Specific Autoantibodies in Patients with Type 1 Diabetes That Developed on a Background of Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by disturbed antibody production and a dysregulated immune system. Aside from recurrent infections, the most common complications of CVID are autoimmune complications, particularly autoimmune cytopenias. To date, type 1 diabetes mellitus (T1D) in combination with CVID has only been described as an unusual complication in several reports, but the true incidence of T1D with CVID remains unknown. We describe 2 patients with a combination of T1D and CVID with serious impairment of antibody production. We also provide a review of the available literature. T1D-specific insulin autoantibodies and autoantibodies to glutamic acid decarboxylase and tyrosine phosphatase IA2 were not detected in either of our patients at the time of diagnosis or during the course of the disease. In both cases, T1D manifestation and diagnosis preceded the discovery of CVID by several years. Following the diagnosis of immunodeficiency and the start of immunoglobulin substitution therapy, their clinical status improved, manifesting as a lower frequency of infections and improved T1D control, with decreased glycosylated hemoglobin A1c values. Based on these reported cases, we assume that T1D might be more frequent than previously reported in patients with CVID. To verify the actual incidence of T1D among CVID patients, we searched the European Society for Immunodeficiencies Registry database, and found 25 cases of T1D in 1,671 listed CVID patients, suggesting a higher occurrence of T1D among CVID patients than previously thought. Early diagnosis and treatment of immunodeficiency improve both the prognosis and the course of CVID, reduce the frequency and severity of infections and may contribute to better management of T1D.

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

“…Pituch‐Noworolska et al in 2013 evaluated autoantibodies in children with CVID and report that antibodies are produced despite impaired humoral immunity, but their level might be lower than immunocompetent individuals affected by autoimmunity. In another study, Milota et al described 2 patients with a combination of T1D and CVID with serious impairment of antibody production. Moreover, autoantibodies were not detected in these patients at the time of diagnosis or during the course of the disease.…”

Autoimmunity in Primary Antibody Deficiencies

“…The most prevalent autoimmune disorder in patients with CVID is autoimmune cytopenia, by far the most common occurring variably in 4-20% (ITP develop in 6-14% and AIHA in 5-7%), but pernicious anemia (1-9%), RA (1-10%), IBD (6-10%), SLE, autoimmune thyroid disease, hepatitis, vitiligo, psoriasis, Sjögren syndrome, and now primary biliary cirrhosis as well as inflammatory relapsing polychondritis have also less frequently been reported [6,69,70,71,72]. It should be noted that autoimmune disorders may be the first or at the time the only clinical manifestation of CVID diagnosis [73,74]. Two separate studies showed that 54% [75] and 62% [76] of subjected CVID patients had the first episode of ITP or AIHA prior to the diagnosis.…”

The prevalence, clinical relevance and origin of autoantibodies in patients with Common variable immunodeficiency on regular immunoglobulin replacement therapy – the results from a prospective observational study

“…Correspondingly, both T1D and AIT may develop in the abscence of speci c autoantibodies. The autoantibody negative cases comprise 3.5-19% from all T1D patiens (22,23), moreover, several seronegative T1D patients were also desribed amongst the CVID patients (10). Autoantibody negative AIT represents approximately 5% of all patients with AIT (24).…”

“…Despite the markedly impaired antibody production, diseases hallmarked by the presence of autoantibodies, such as Autoimmune hemolytic anemia (AIHA) or Immune thrombocytopenic purpura (ITP), are amongst the most commonly diagnosed autoimmune complications in CVID patients, found in up to 38.9% of patients (7,8). An increased prevalence of other autoimmune diseases associated with the tissue speci c autoantibodies in comparison to general population was also reported, such as Autoimmune thyroiditis (AIT) or Type 1 diabetes (T1D) revealed in 0.8-8.7%, and 0.8-7.1% of CVID patients respectively (7,9,10). The mainstay of CVID management is a regular, long-term immunoglobulin replacement therapy (IRT).…”