Free light chains of immunoglobulins in patients with systemic sclerosis: correlations with lung involvement and inflammatory milieu

Bosello, Silvia Laura; Basile, Umberto; Lorenzis, Enrico De; Gulli, Francesca; Canestrari, Giorgia; Napodano, Cecilia; Parisi, Federico; Pocino, Krizia; Mario, Clara Di; Tolusso, Barbara; Ferraccioli, Gianfranco; Gremese, Elisa

doi:10.1136/jclinpath-2017-204656

Cited by 19 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the oxidative stress observed in SSc could promote the differentiation of B-cell into plasmocytes and lead to an increased antibody production, and amongst them, autoantibodies. Consistent with this idea, the level of immunoglobulin light chains in sera was showed to be increased by 1.3 fold in SSc patients compared to healthy controls in 2 independent studies [46], [47].…”

Section: Ros and Autoimmunity In Sscsupporting

confidence: 57%

Implication of oxidative stress in the pathogenesis of systemic sclerosis via inflammation, autoimmunity and fibrosis

et al. 2019

View full text Add to dashboard Cite

Systemic sclerosis is an autoimmune disorder characterized by inflammation and a progressive fibrosis affecting the skin and visceral organs. Over the last two decades, it became clear that oxidative stress plays a key role in its pathogenesis. In this review, we highlighted the role of ROS in the various pathological components of systemic sclerosis, namely the inflammatory, the autoimmune and the fibrotic processes. We also discussed how these pathological processes can induce ROS overproduction, thus maintaining a vicious circle. Finally, we summarized the therapeutic approaches targeting oxidative stress tested in systemic sclerosis, in cells, animal models and patients.

show abstract

Section: Ros and Autoimmunity In Sscsupporting

confidence: 57%

Implication of oxidative stress in the pathogenesis of systemic sclerosis via inflammation, autoimmunity and fibrosis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Specifically, serum κ chains and κ/λ ratios were significantly higher in systemic sclerosis and correlated with disease activity. 11 Moreover, κ chains were significantly and strongly correlated with disease activity in Sjögren syndrome, and patients with systemic lupus erythematosus demonstrated elevated concentrations of serum FLC (mainly κ chains), with a strong inverse correlation having been found between the κ chain levels and the C3 levels. 11 , 12 CSF κ FLC levels have a high sensitivity and specificity for the diagnosis of MS, and they can predict conversion from a clinically isolated syndrome to MS. 15 – 17 …”

Section: Discussionmentioning

confidence: 94%

“…9 An increase in free light chain (FLC) production has been reported in several autoimmune diseases. [11][12][13][14][15][16][17] To the best of our knowledge, only 1 study has evaluated FLC levels in MG, and it reported an elevation of both κ FLC and λ FLC in their 34 study patients. 18 We hypothesized that κ FLC and λ FLC levels may be biomarkers for MG, especially for SN-MG for which diagnosis can be difficult.…”

mentioning

confidence: 97%

See 1 more Smart Citation

High κ free light chain is a potential biomarker for double seronegative and ocular myasthenia gravis

Wilf-Yarkoni

Alkalay

Brenner

et al. 2020

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

ObjectiveTo investigate the hypothesis that free light chain (FLC) sera levels could serve as a biomarker for myasthenia gravis (MG), especially for the subgroups of seronegative MG and ocular MG.MethodsSera from 73 patients with MG (20 seronegative for antiacetylcholine receptor [AChR] and anti–muscle-specific kinase and 53 positive for anti-AChR, which were clinically divided into 24 patients with ocular type, 45 with generalized type, and 4 with unequivocal clinical manifestation) and 49 healthy controls were studied for κ FLC and λ FLC levels with the Freelite human FLC kits.ResultsThe κ but not the λ levels of FLC were significantly increased in the patients with MG, including those with double seronegative MG and ocular MG, compared with the healthy controls. The specificity for double seronegative MG and ocular MG were both 98.0% when κ FLC was ≥25.0 mg/L. Increased κ FLC levels were not affected by the patient's sex, age at MG onset, the presence of thymic pathology, or different treatments.ConclusionsElevated serum κ FLC may serve as a biomarker for MG in suspected patients who are double seronegative and in those with only ocular manifestations when serology is inconclusive.Classification of evidenceThis study provides Class III evidence that high κ FLC levels distinguished patients with MG, including those who were double seronegative, from healthy controls.

show abstract

“…Oxidative stress and activation of the immune system are important mechanisms that are hypothesized to mediate associations of AP and chronic diseases, i.e., cardiovascular diseases. A modulation of the immune system may further lead to autoimmune diseases such as multiple sclerosis (Bosello et al 2018), rheumatoid arthrosis (Gottenberg et al 2007), or hypersensitivity-like responses (Redegeld et al 2002). The immune system evolves from a complex interplay of immune cells, biological structures, and processes to defend the organism against pathogens.…”

Section: Introductionmentioning

confidence: 99%

Air Pollution and Polyclonal Elevation of Serum Free Light Chains: An Assessment of Adaptive Immune Responses in the Prospective Heinz Nixdorf Recall Study

Ohlwein

Hennig

Lucht

et al. 2021

Environ Health Perspect

View full text Add to dashboard Cite

Background: Residential exposure to air pollution (AP) has been shown to activate the immune system (IS). Although innate immune responses to AP have been studied extensively, investigations on the adaptive IS are scarce. Objectives: The aim of this study was to investigate the association between short- to long-term AP exposure and polyclonal free light chains (FLC) produced by plasma cells. Methods: We used repeated data from three examinations ( : 2000–2003; : 2006–2008; and : 2011–2015) of the population-based German Heinz Nixdorf Recall cohort of initially 4,814 participants (45–75 y old). Residential exposure to total and source-specific particulate matter (PM) with an aerodynamic diameter of 10 or ( and respectively), nitrogen dioxide ( ), and particle number concentrations (accumulation mode; ) was estimated using a chemistry transport model with different time windows (1- to 365-d mean ± standard deviation) before blood draw. We applied linear mixed models with a random participant intercept to estimate associations between total, traffic- and industry-related AP exposures and log-transformed FLC, controlling for examination time, sociodemographic and lifestyle variables, estimated glomerular filtration rate and season. Results: Analyzing 9,933 observations from 4,455 participants, we observed generally positive associations between AP exposures and FLC. We observed strongest associations with middle-term exposures, e.g., 3.0% increase in FLC (95% confidence interval: 1.8%, 4.3%) per interquartile range increase in 91-d mean of ( ). Across the different pollutants, showed strongest associations with FLC, followed by and . Effect estimates for traffic-related exposures were mostly higher compared with total exposures. Although and estimates remained stable upon adjustment for PM, PM estimates decreased considerably upon adjustment for and . Discussion: Our results suggest that middle-term AP exposures in particular might be positively associated with activation of the adaptive IS. Traffic-related PM, , and showed strongest associations. https://doi.org/10.1289/EHP7164

show abstract

Free light chains of immunoglobulins in patients with systemic sclerosis: correlations with lung involvement and inflammatory milieu

Abstract: FLC levels are elevated in SSc and high levels are associated with lung involvement and with a higher degree of inflammation, supporting a possible role of B cell activation in the pathophysiology of the disease.

Cited by 19 publications

References 44 publications

Implication of oxidative stress in the pathogenesis of systemic sclerosis via inflammation, autoimmunity and fibrosis

Implication of oxidative stress in the pathogenesis of systemic sclerosis via inflammation, autoimmunity and fibrosis

High κ free light chain is a potential biomarker for double seronegative and ocular myasthenia gravis

Air Pollution and Polyclonal Elevation of Serum Free Light Chains: An Assessment of Adaptive Immune Responses in the Prospective Heinz Nixdorf Recall Study

Contact Info

Product

Resources

About