Home Immunity More immune system research needed to understand the pathobiology of PAH

More immune system research needed to understand the pathobiology of PAH



While research has examined the implications of the immune system and its contributions to pulmonary arterial hypertension, more research is needed to understand the pathobiology of the disease.

While the relationship between the immune system, autoimmunity, and pulmonary arterial hypertension (PAH) has been studied for years, the pathobiology of PAH requires further investigation, according to a review published in Pulmonary and therapeutic pharmacology.

PAH causes narrowing of the lumen of the small and medium pulmonary arteries and the development of occlusive cell damage in the precapillary pulmonary arterioles, resulting in irreversible pulmonary arterial remodeling. The disease results in increased infiltration of immune cells such as monocytes, macrophages, mast cells, dendritic cells (DC), CD4 + and CD8 + T cells, and B cells.

Of the group of conditions that make up PAH, idiopathic PAH (PAH) refers to PAH that is not associated with any identifiable cause. Associated PAH (APAH) is associated with human immunodeficiency virus, congenital heart disease, exposure to toxins and drugs, rheumatoid arthritis, telangiectasia, Raynaud’s phenomenon, systemic sclerosis, Systemic lupus erythematosus (SLE) and schistosomiasis. Hereditary / Familial PAH (HPAH) encompasses PAH caused by mutations in associated genes and includes patients with a family history of the disease.

Regardless of the cause and type of PAH, patients with PAH have significant inflammation with an infiltration of immune cells into their lungs. Elevated levels of inflammatory markers, primarily interleukin (IL) -6, IL-8, IL-10, and IL-12p70, found in the serum of patients with PAH are predictors of disease severity and patient survival.

Pulmonary vascular inflammation has also been observed in patients with PAH associated with SLE (PAH-LES). Immunosuppressive therapy has shown positive results for patients with PAH-SLE who present with inflammation, indicating inflammation and autoimmunity in these patients.

Recent preclinical studies examining the importance of adaptive immunity in patients with PAH have shown that the number of natural killer cells and their levels of function are reduced along with reduced expression of immunoglobin-like receptors. (Ig) killer cells. The number of blood plasmablasts has been found to increase in patients with IPAH over time, producing antibodies of the IgA isotype.

Infiltrating immune cells such as cytotoxic and helper T lymphocytes, B lymphocytes, neutrophils, monocytes and macrophages, natural killer cells, DCs and mast cells have been observed in lesions of the pulmonary vessels of patients with HTAP. Macrophage infiltration plays a key role in the pathogenesis of PAH by initiating inflammation, damaging endothelial cells, and secreting factors that induce arteriole musculization, such as vascular endothelial growth factor and factor growth derived from platelets.

The presence of autoantibodies against pulmonary endothelial cells and fibroblasts highlights the role of B cells in patients with PAH. High levels of plasmablasts and levels of IgA antibody production in patients with IPAH give rise to anti-endothelial cell IgA autoantibodies, indicating a role of autoimmunity and autoimmune damage in the pathogenesis of IPAH.

Effective treatment methods are essential for patients with PAH, as the disease can lead to heart failure and death within 2 to 3 years if not treated promptly. Current therapeutic approaches include cytokine treatments and the use of immunomodulatory drugs.

Future methods of treating patients with PAH could involve pharmacogenomic approaches, which would help identify people who may benefit from treatment. A possible direction of therapeutic interest involves clinical trials of combination pharmacotherapy of investigational targeted agents with traditional drugs.

Further research regarding the pathology of PAH, pathogenesis and the relationship between the 2, as well as the implications for other conditions, is needed to develop targeted therapies, appropriate diagnostics and prevention methods, concluded the authors.


Han Z, Li X, Cui X, Yuan H, and Wang H. The roles of the immune system and autoimmunity in pulmonary arterial hypertension: a review. Pulm Pharmacol Ther. Published online November 2, 2021. doi: 10.1016 / j.pupt.2021.102094