The Behaviour of Serum Survivin in Patients With Lupus Nephritis.

Background: Systemic lupus erythematosus (SLE) is a chronic, multi phenotypic, autoimmune inflammatory disease and renal involvement significantly worsens its prognosis. Apoptosis dysregulation plays a key pathogenic role. Survivin, a protein from the apoptosis inhibitors family, has been considered a promising strategy in cancer therapy and evaluated as one of the regulatory pathways in the scenario of immune-mediated disorders. Objective: This study aims to explore survivin behaviour in SLE patients with lupus nephritis (LN), assessing its potential as a therapeutic and prognostic biomarker. Methods: 297 SLE patients were classified based on the American College of Rheumatology (ACR) 1997 criteria, from 2000 to 2015. In a cross-sectional study, the serum level of survivin was measured by an ELISA test and compared between 200 SLE individuals and healthy controls. In a longitudinal cohort, 97 patients with active LN had the concentration of survinin measured, before and after treatment with cyclophosphamide pulse therapy. Results: The serum concentration of survivin was significantly lower in the SLE group than in healthy controls, regardless of concomitant NL or disease activity. The longitudinal evaluation revealed a significant reduction in survivin serum level after treatment. However, survivin rates were not able to discriminate groups that achieved remission from those that maintained nephritis activity. Conclusion: Our study suggests that survivin levels in SLE patients are lower than in the general population. Even so, its use as a biomarker in SLE seems limited, not reflecting disease activity or response to LN treatment, as in other contexts.

Clinical and laboratory evaluation of sicca complaints: distinctive aspects of primary, secondary and non-Sjogren syndrome.

BACKGROUND: Sjögren Syndrome (SS) is a systemic autoimmune disease with a wide spectrum of manifestations that can lead to misdiagnosis. This study describes and compares demographic, clinical, serological, and histopathological data from subjects with SS and non-Sjögren Syndrome (NSS). It also details specific features within the primary SS (pSS) and secondary SS (sSS) groups identifying sub-groups. METHODS: The sample included individuals referred to an academic medical center in Brazil for investigation of SS from 2012 to 2020. Patients were retrospectively classified as primary SS (pSS), secondary SS (sSS), or NSS, based on the American-European Consensus Group criteria (AECG-2002), after multi-professional clinical and laboratory evaluation. RESULTS: A total of 676 individuals were screened and 510 (75.4%) completed the assessments; 198 patients were classified as pSS, 149 as sSS, and 163 as NSS. Symptoms and glandular dysfunction tests were similar in the groups. Concerning pSS, extraglandular manifestations were present in 59% of patients; the elderly had more dry symptoms and peripheral neurological disorders; and 2.5% developed non-Hodgkin lymphoma. In sSS, each overlap promoted distinct clinical and laboratory variants. Several alternative diagnoses were identified as a cause of sicca complex in NSS group. CONCLUSIONS: The diagnosis of SS remains a challenge behind dryness. Up to 31% of the suspected cases had other conditions associated to the symptoms. Histopathological analysis of LSG and SSa determined the diagnostic. Aging in pSS and overlap disease in sSS were responsible for distinct phenotypes and characteristic sub-groups in SS.

Neurological and Inflammatory Manifestations in Sjögren's Syndrome: The Role of the Kynurenine Metabolic Pathway.

For decades, neurological, psychological, and cognitive alterations, as well as other glandular manifestations (EGM), have been described and are being considered to be part of Sjögren's syndrome (SS). Dry eye and dry mouth are major findings in SS. The lacrimal glands (LG), ocular surface (OS), and salivary glands (SG) are linked to the central nervous system (CNS) at the brainstem and hippocampus. Once compromised, these CNS sites may be responsible for autonomic and functional disturbances that are related to major and EGM in SS. Recent studies have confirmed that the kynurenine metabolic pathway (KP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating indoleamine 2,3-dioxygenase (IDO) in SS. This pathway interferes with serotonergic and glutamatergic neurotransmission, mostly in the hippocampus and other structures of the CNS. Therefore, it is plausible that KP induces neurological manifestations and contributes to the discrepancy between symptoms and signs, including manifestations of hyperalgesia and depression in SS patients with weaker signs of sicca, for example. Observations from clinical studies in acquired immune deficiency syndrome (AIDS), graft-versus-host disease, and lupus, as well as from experimental studies, support this hypothesis. However, the obtained results for SS are controversial, as discussed in this study. Therapeutic strategies have been reexamined and new options designed and tested to regulate the KP. In the future, the confirmation and application of this concept may help to elucidate the mosaic of SS manifestations.