Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy

Abstract

The contribution of the decline in thymic activity for the emergence of autoimmunity is still debatable. Immune-competent adults submitted to complete thymectomy early in life provide a unique model to address this question. We applied here strict criteria to identify adults lacking thymic activity based on sjTREC levels, to exclude thymic rebound and/or ectopic thymuses. In agreement, they featured severe naïve CD4 T-cell depletion and contraction of T-cell receptor diversity. Notwithstanding this, there was neither increased incidence of autoimmune disease in comparison with age-matched controls nor significant changes in their IgG/IgA/IgM/IgE autoreactivity profiles, as assessed through extensive arrays. We reasoned that the observed relative preservation of the regulatory T-cell compartment, including maintenance of naïve regulatory CD4 T-cells, may contribute to limit the emergence of autoimmunity upon thymectomy. Our findings have implications in other clinical settings with impaired thymic activity, and are particularly relevant to studies of autoimmunity in ageing.

Fig 1. IgG autoantibody profiles.

Heatmap of serum IgG autoantibody reactivity in adults thymectomized early in infancy (T) and controls (C) clustered by autoantigen and subject group. Reactivity intensity was normalized and log2-transformed, and 121 autoantibodies meeting minimal net fluorescence intensity requirements are presented. Key color bar corresponds to quantified reactivity.

Fig 2. IgA autoantibody profile.

Heatmaps of serum IgA autoantibody reactivity in adults thymectomized early in infancy (T) and controls (C), clustered by autoantigen and subject group. Reactivity intensities were normalized and log2-transformed; and 121 IgA autoantibodies meeting minimal net fluorescence intensity requirements are presented. Key color bar corresponds to quantified reactivity.

Fig 3. IgM autoantibody profile.

Heatmaps of serum IgM autoantibody reactivity in adults thymectomized early in infancy (T) and controls (C), clustered by autoantigen and subject group. Reactivity intensities were normalized and log2-transformed; and 122 IgM autoantibodies meeting minimal net fluorescence intensity requirements are presented. Key color bar corresponds to quantified reactivity.

Fig 4. IgE autoantibody profiles.

Heatmaps of serum IgE autoantibody reactivities in adults thymectomized early in infancy (T) and controls (C) clustered by autoantigen and subject group. Reactivity intensities were normalized and log2-transformed, and 100 IgE autoantibodies meeting minimal net fluorescence intensity requirements are presented. Key color bars correspond to quantified reactivity.