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.