Introduction
Systemic sclerosis (SSc) is an autoimmune disease characterized by microvascular dysfunction, multi-systemic fibrosis and autoantibodies production. Immune dysregulation, vasculopathy and collagen accumulation with fibrosis in the skin and internal organs lead to major complications that negatively affect quality of life [1]. Although the pathogenesis of SSc remains poorly understood, activation and dysregulation of B cells play a key role. In SSc patients, abnormal immunological mechanisms promote survival and activation of self-reactive B cells, able to secrete inflammatory mediators and/or profibrotic cytokines inducing collagen secretion by fibroblast. Noteworthy, both serum and skin of SSc patients displayed increased levels of B lymphocyte stimulator (BAFF), a B cell survival factor that supports autoreactive B cells and prevents their deletion [2]. B-cell activation causes polyclonal synthesis of immunoglobulins and release of circulating Immunoglobulin- (Ig-) free light chains in serum (sFLC). FLCs, produced in slight excess of heavy chains during the synthesis of intact Ig by plasma cells, have a short half-life of 2-6 h in serum, due to a rapid removal by the kidneys: more than 99% of sFLC, filtered by the glomerulus, is reabsorbed from the cells of the proximal convoluted tubule resulting in the traces amounts in the urine (10-30 mg/day) [3]. Therefore, in subjects with normal kidney function, their serum levels can be considered as a direct biomarker of B cell activity, which explains the growing interest of clinicians. More important, the well-demonstrated FLC contribution to inflammation in experimental disease models sparked a new light into their pathogenic role in different chronic autoimmune-based inflammatory diseases [4]. An increased level of polyclonal sFLC, described in several autoimmune diseases (ADs), may represent a reliable potential biomarker of disease evolution or remission [5]. In SSc high sFLC is independently associated with interstitial lung disease (ILD), activity and severity disease [6].
Inflammatory/autoimmune-related symptoms complained by corona virus disease 2019 (COVID-19) patients, reflect the strong pathogenetic association between the severe acute syndrome corona virus2 (SARS-CoV-2) infection and autoimmunity [7, 8]. COVID-19 subsequent effects of an inflammatory-immune dysregulation significantly impaired the management of chronic rheumatic diseases, including systemic sclerosis. Cytokines storm cascade virus-triggered raises the possibility of severe endotheliopathy with a higher risk, in SSc patients, of worsening progression into an endothelial dysfunction [9].
To our knowledge, only two reports assessed sFLC levels in SSc patients but none regarding urine FLC (u-FLC) and their potential role in the SSc [6, 10]
In this study, we aimed to analyze both serum and urine FLC levels in SSc patients in comparison healthy controls (HC) and to evaluate their correlations with activity and severity of disease.