RESUMO
INTRODUCTION: Systemic sclerosis (SSc) affects the connective tissue and leads to an abnormal fibrotic process in the skin and internal organs. Epidermal Growth Factor Receptor (EGFR) is able to induce cell proliferation and differentiation, and its expression is increased in SSc patients with pulmonary artery hypertension and in skin biopsies in patients with scleroderma. To date, no data on esophageal expression of EGFR are available in SSc patients. We aimed to evaluate whether the pro-fibrogenic pathways of SSc may affect EGFR expression in the esophagus. METHODS: A retrospective analysis included patients with SSc and control subjects suffering from gastroesophageal reflux symptoms. Endoscopic assessment and histopathologic analyses were performed in all subjects and the presence of microscopic esophagitis was used to distinguish patients with normal esophageal mucosa and subjects with non-erosive reflux disease. EGFR expression was measured in all subjects. RESULTS: A total of 35 patients with SSc were included, while the control group included 67 non-SSc patients. EGFR expression at the Z-line was higher in SSc patients than non-SSc patients in absence of microscopic esophagitis (median 65 %, IQR 56-71 % vs 42 %, IQR 37-54 %, p < 0.001). Microscopic esophagitis was found in 60 % of patients with SSc and 62.7 % of control patients, and EGFR expression was significantly higher in patients presenting microscopic esophagitis both in SSc and non-SSc patients. CONCLUSION: The EGFR hyperexpression may be due to SSc and/or reflux-related damage in patients with microscopic esophagitis. Further studies are warranted to answer open questions and provide a possible role of EGFR in terms of diagnosis, prognosis, and therapy.
Assuntos
Esofagite , Refluxo Gastroesofágico , Escleroderma Sistêmico , Humanos , Estudos Retrospectivos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/patologia , Receptores ErbBRESUMO
Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.