Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão

Abstract

Systemic Lupus Erythematosus (SLE) is a multifactorial inflammatory autoimmune disease caused by an immune dysfunction characterized by a breakdown of immune self-tolerance, activation of autoreactive T lymphocytes and B lymphocyte hyperactivity. The nucleotides and nucleoside adenine, such as ATP and adenosine, are key components in inflammatory and immune processes, including the modulation of lymphocyte functions. Their extracellular levels are regulated by ectoenzymes such as E-NTPDase which hydrolyzes ATP / ADP to AMP; E-5'-nucleotidase that degrades AMP to adenosine and E-adenosine deaminase (E-ADA) that converts adenosine to inosine. In this work, we determined the activity and expression of E-NTPDase, E-5'-nucleotidase expression, and E-ADA activity in lymphocytes, as well as ADA activity and nucleotide and nucleoside concentration in the serum of SLE patients. We also aimed to fill in some gaps we observed in the literature by writing a review article regarding purinergic signaling and SLE. Thirty-five patients from the University Hospital of Santa Maria (HUSM) with a diagnosis of SLE were selected, based on the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and 30 controls, from which blood samples were collected for the analyzes. The results showed an increase in the serum ATP concentration, possibly as a result of inflammation, and a decrease in adenosine levels in SLE patients. Increased activity (31%) and expression (37%) of E-NTPDase were observed in lymphocytes of SLE patients. The activity of E-ADA was also increased by approximately 42% in the lymphocytes of these patients. The serum ADA activity was reduced by 57%. Regarding the expression of E-5'-nucleotidase in lymphocytes of patients with SLE, no differences were observed. The increase observed in the activity and expression of E-NTPDase could represent a mechanism to help in the control of inflammation, since this enzyme exerts anti-inflammatory effects through the removal of ATP. However, increased E-ADA activity in lymphocytes could favor a Th1 response and limit the anti-inflammatory effects of adenosine. On the other hand, serum ADA has been shown to be decreased due to the impaired macrophage function present in these patients since most of the serum ADA comes from these cells. When we checked a gap in the literature regarding purinergic signaling and SLE, we decided to write a review on the topic to elucidate the effects of ATP and E-NTPDase on SLE and contribute to the understanding of SLE in this context. In view of this, we conclude that the NTPDase, ADA and the purinergic pathway play an important role in modulating the immune and inflammatory response in SLE patients.