Evaluate the role of Epstein-Barr virus infection in PAH (Idiopathic and connective tissue disease).

This by obtaining a blood sample from the PAH patients undergoing right heart cathetrization as well as obtaining the endothelial cells from the balloon tipped catheters and extracting the EBV virus to detect its presence.

IgG, IgM and PCR for EBV tests will be done.

About Pulmonary Hypertension Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions combined with a variety of cardiovascular and respiratory diseases. It is defined by a mean pulmonary arterial pressure (mPAP) of more than 20 mmHg at rest (Humbert, M.et al., 2022).

Pulmonary arterial hypertension (PAH) is a condition characterized by vascular proliferation, leading to increased vascular resistance and right heart dysfunction. PAH may be idiopathic (Idiopathic Pulmonary Arterial Hypertension IPAH; previously known as primary pulmonary hypertension, PPH) or associated with other conditions or exposures, including connective tissue diseases, HIV infection, portal hypertension, and anorexigenic drug ingestion (Humbert, M.et al., 2022).

About Chronic active Epstein-Barr virus Chronic Active Epstein-Barr virus (CAEBV) disease is usually defined as a chronic illness lasting at least 6 months, an increased EBV level in either the tissue or the blood, and lack of evidence of a known underlying immunodeficiency. It may be associated with Burkitt lymphoma and nasopharyngeal carcinoma, Hodgkin lymphoma, peripheral T cell lymphoma, angioimmunoblastic T cell lymphoma, and extranodal NK/T cell lymphoma (Kimura et al., 2017).

CAEBV is characterized by an unusual pattern of anti-EBV antibodies and may be associated with cardiovascular abnormalities (Hashimoto et al., 2011).

Diagnosis of Epstein-Barr virus (EBV) infection is based on clinical symptoms and serological markers, including the following: immunoglobulin G (IgG) and IgM antibodies to the viral capsid antigen (VCA), heterophile antibodies, and IgG antibodies to the EBV early antigen-diffuse (EA-D) and nuclear antigen (EBNA-1)(Klutts JS. Et al., 2009).

Elevated levels of EBV DNA in the blood are more specific for CAEBV than elevated levels of EBV antibodies (Kimura H. et al., 2017).

Role of EBV in PAH The relationships between EBV and autoimmune diseases are complex and involve several mechanisms. A proposed scenario was the interrelation between genetic predisposition and EBV infection, a cross-reaction between self antigens and EBV viral proteins, the development of autoantibodies (anti-Sm or anti-Ro antibodies in SLE, anti-CCP antibodies in RA), an epitope-spreading process that can lead to the development of additional non-cross-reactive autoepitopes, and finally the clinical manifestations (Poole BD et al.,2006).

EBV has multiple impacts on host immunity and can adapt to its environment. For instance, EBV produces an IL-10-like cytokine, it can modulate IL-6 release, it induces the production of TNF-a by infected B cells, and it can inhibit apoptosis of infected B cells by the production of a Bcl-2 homolog. All these biological properties of EBV are relevant to, and can contribute to, the pathophysiology of autoimmune disorders (Toussirot É et al.,2008).

The pathophysiology of the development of PAH in CAEBV is unclear. It may be related to lymphocytic infiltration and the resultant damage to the pulmonary vascular endothelium caused by EBV infection or may occur secondary to the vascular damage caused by inflammatory reactions induced by EBV infection (Gotoh K. et al., 2008).

Another is EBV-induced high levels of inflammatory cytokines resulting in inflammatory change (Fujiwara M. et al., 2003).

Inclusion Criteria:

• Group 1 PAH (Idiopathic ) Group 1 PAH ( Connective tissue disease including SLE, Systemic sclerosis and mixed connective tissue disease) Above 18 years

Exclusion Criteria:

• Other Groups of Pulmonary hypertension Patients refusing written consent or participation

PAH patients (Idiopathic and connective tissue disease; inclusing SLE , systemic sclerosis and mixed connective tissue disease).

Control group: Healthy individuals only blood samples withdrawn