Immune responses to self-antigens in asthma patients: clinical and immunopathological implications

Abstract

Asthma leads to chronic airway inflammation that shares pathological features of chronic rejection after lung transplantation. Due to significant role of autoimmunity in chronic rejection, we hypothesized that immunity to self-antigens may also be present in asthma. The goal was to define immune responses to self-antigens in patients with asthma. Blood and clinical data were collected from 99 asthmatics and 60 controls. Serum was analyzed for antibodies (Abs) to Collagen V (ColV) by ELISA and correlated with disease severity. Asthmatics' sera were tested in human protein array to determine immune responses to other self-antigens. Asthmatics had higher concentration of Abs to ColV (predominantly IgG isotype) compared to control (p < 0.01). These Abs correlated with severe asthma (p<0.01) and corticosteroid use (p=0.032). Additionally, Abs to novel self-antigens epidermal group factor receptor (EGFr), activin A type 1 receptor, and alpha-catenin (α-catenin) were detected in asthmatics. We conclude that Abs to self-antigens (ColV, EGFr, Activin A type 1 receptor, and α-catenin) are present in asthmatics sera correlating with clinical disease. Epithelial damage from airway inflammation during asthma may result in exposure of cryptic self-antigens or their determinants resulting in immune response to self-antigens and these may contribute to pathogenesis of asthma.

Lung Injury Combined with Loss of Regulatory T Cells Leads to De Novo Lung-Restricted Autoimmunity

“…Growing body of evidence supports the presence of lung-restricted immunity in patients with chronic lung disease (1–5). While the effects of lung-restricted antibodies in non-transplant patients remain unclear, they have been shown to significantly reduce allograft survival by causing both early (2–6) and chronic lung allograft rejection (36).…”

“…Patients with chronic lung disease can develop immunity against lung-restricted antigens (1). In fact, over one-third of patients with end-stage lung disease who are undergoing lung transplantation have pre-existing non-human leukocyte antibodies (nHLAbs) against lung-restricted self-antigens collagen type V (ColV) and k-alpha1 tubulin V (KAT) (2–5).…”

Lung-Restricted Antibodies Mediate Primary Graft Dysfunction and Prevent Allotolerance after Murine Lung Transplantation

“…A growing body of evidence supports the presence of lung-restricted immunity in patients with chronic lung disease (8)(9)(10)(11)44). Although the effects of lung-restricted antibodies in non-transplant patients remains unclear, they have been shown to significantly reduce the allograft survival by causing both early (8)(9)(10)(11)18) and chronic lung allograft rejection (45).…”

Update on lung transplantation: programmes, patients and prospects

“…As well as validated antigen targets like collagen V, the intracellular DAMP content released on necrotic cell death, especially where innate signalling molecules including activin A are strongly activated, may trigger the formation of reactive T-cells and autoantibodies [377,378]. Given that PGD can stimulate innate immunity which primes adaptive immunity, thereby shaping adaptive immunity-mediated T-and B cell effector pathways, it is perhaps not surprising that panels of acutely altered intracellular protein biomarkers correspond well to patterns of autoantibodies observed in chronic graft rejects [376].…”