NAA and Pulmonary Diseases
There has been much research focusing on the roles autoantibodies play in different types of pulmonary diseases. Although the research is not comprehensive and in-depth, the importance of autoantibodies is obvious in most pulmonary diseases.
- Pulmonary arterial hypertension (PAH)
- Chronic obstructive pulmonary disease (COPD)
- Interstitial lung diseases (ILDs)
Several autoantibodies have been reported in Pulmonary arterial hypertension (PAH), in particular Idiopathic pulmonary arterial hypertension (IPAH) and systemic sclerosis (SSc)-associated PAH (SSc-PAH). Some SSc clinical features are associated with subspecificities of anti-centromeric proteins (CENP)-A antibodies. Another research reported a unique case of PAH associated with anti-SSA/Ro antibodies in the absence of clinical signs of SS, which highlights the potential for further evaluation of anti-SSA/Ro antibodies as a possible PAH marker. Endothelin receptor type A (ETRA) autoantibodies are identified as a biomarker for mechanistic relevance in SLE. These autoantibodies may mediate PAH development in systemic lupus erythematosus (SLE). Anti-Ang receptor type-1 and anti-endothelin receptor type A antibodies are more frequent in SSc-PAH/connective tissue diseasePAH compared with other forms of pulmonary hypertension and may serve as predictive and prognostic biomarkers in SSc-PAH. Both antibodies may contribute to SSc-PAH via increased vascular endothelial reactivity and induction of pulmonary vasculopathy.
Table 1. Autoantibodies in different types of PAH
| Autoantibody | Type of PAH | Role |
|---|---|---|
|
Anti-CENP-A Anti-SSA/Ro Anti-U1 RNP Anti-ETRA Antifibrillarin Anti-EC Anti-dsDNA Antifibroblast |
SSc-PAH SSc-PAH CTD-PAH, SSc-PAH SLE-PAH, SSc-PAH SSc-PAH SSc-PAH CTD-PAH SSc-PAH, IPAH |
Unknown Unknown Unknown Unknown Upregulate adhesion molecules Activate EC, induce the expression of adhesion molecules, trigger apoptosis Upregulate adhesion molecules Activate fibroblasts, induce collagen synthesis |
Antibodies from sera of patients with SSc induce a pro-adhesive and proinflammatory response in normal fibroblasts. Patients with IPAH and PAH-SSc have IgG antifibroblast antibodies present in their sera which have distinct reactivity profiles under these two conditions. A two-dimension immunoblotting experiment showed that fibroblasts antigens which are recognized by serum IgG from IPAH and SSc-PAH patients include proteins involved in the regulation of cytoskeletal function, cell contraction, cell and oxidative stress, cell energy metabolism, and other pathways that play key roles in cell biology and maintenance of homeostasis. Although the specific membrane antigen targeted by these autoantibodies has not yet been determined, it is likely that the antibodies can react with membrane components, since they typically bind to unpermeabilized fibroblasts, thereby mediating the release of cytokines and growth factors, which in turn might contribute to the pathogenesis of vascular remodeling in PAH.
Chronic obstructive pulmonary disease (COPD) is a major public health problem affecting more than 200 million people worldwide and leading to millions of deaths annually. Autoantibodies are present in both COPD patients and in corresponding animal models, particularly those involving emphysema. Severe COPD with emphysema is associated with HLA II alleles which are associated with most autoimmune diseases. In animal models, autoantibodies of COPD can induce a COPD-like disease phenotype. In addition, COPD patients are characterized by increased numbers of B cells, plasma cells, and B cell-rich lymphoid follicles that correlate directly with disease severity, which support the role of autoantibodies in the development of COPD.
Fig.1. Proposed contribution of natural autoantibodies to chronic pulmonary diseases. (Fukushima, 2020)
Interstitial lung diseases (ILDs) are heterogeneous diseases that affect the lung parenchyma in a diffuse and multicompartmental manner, being characterized by different combinations of inflammation and fibrosis; the understanding of ILDs has increased dramatically in recent years. In a recent study aimed at evaluating the prevalence of occult CTD in all ILD patients presenting exclusively with respiratory symptoms, the most common autoantibodies were ANF, in 56%, rheumatoid factor (RF), in 31%, and anti-Ro, in 15%. Inflammatory myopathies were present in 50% of cases, and the histological pattern most associated with CTD is NSIP. An independent analysis of the data from that study shows that, of the 80 patients who showed no association with CTD at the end of the study period, 34 (42.5%) tested positive for ANF (7 of whom had ANF titer greater than or equal to 1:640) and 11 (16.3%) had a nucleolar pattern, which is highly specific for PSS. These findings strongly suggest the presence of occult CTD.
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Autoantibody has shown great potential in the application of different types of pulmonary diseases and has absorbed many researchers focusing on it. Creative Biolabs is professional in the field of antibodies and we also have extensive experience in autoantibody research. Based on years of accumulation, we have established a comprehensive autoantibody research platform providing various autoantibody relevant services and products:
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Reference:
- Fukushima, K.; et al. Natural Autoantibodies in Chronic Pulmonary Diseases. Int J Mol Sci. 2020, 21(3).
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