Serum immunoglobulin free light chains and their association with clinical phenotypes, serology and activity in patients with IgG4-related disease

Eduardo Martín-Nares,Teresa Romero-Maceda,Blanca Estela Santinelli-Núñez,Reynerio Fagundo-Sierra,Karla Calderón-Vasquez,Vanessa Saavedra-González,Gabriela Hernandez-Molina

doi:10.1038/s41598-021-81321-5

Abstract

The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren’s syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.

Highlights

The clinical utility of serum immunoglobulin free light chains in IgG4-related disease (IgG4-RD) is unknown
Κ/λ ratio; serum immunoglobulin free light chains (sFLC) levels correlated with systemic activity and their levels were modified by treatment with rituximab and abatacept, showing a sensitivity to c hange[4]
In this study we demonstrated that a substantial proportion of patients with IgG4-RD had high levels of sFLC, and their assessment may not be useful for distinguishing from other conditions, it may be valuable as a biomarker of disease activity and multiorgan and renal involvement

Summary

Introduction

The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Both tools had their limitations: IgG4 levels may be normal in up to a third of patients with IgG4-RD11,12 and could be elevated in other conditions that are typically part of the differential diagnosis with IgG4-RD such as pancreatic malignancies, Erdheim-Chester disease and systemic v asculitides[13,14,15,16]; whereas, oligoclonal plasmablasts had a better specificity and positive predictive value, but their determination by flow cytometry is not accessible Due to these shortcomings, different biomarkers have been proposed for IgG4-RD such as serum soluble IL-2 receptor, cc-chemokine ligand 18 and B cell-activating factor of the tumor necrosis factor family[17,18,19]

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