Immunoglobulin Free Light Chains in Severe Asthma Patient: could they be a new biomarker?
Caruso C.1*, Ciasca G.2, Baglivo I.3, Di Santo R.2, Gasbarrini A.3, Firinu D.4, Bagnasco D.5, Passalacqua G.5, Schiappoli M.6, Caminati M.7, Canonica G.W.8-9, Heffler E. 8-9, Crimi C.10, Intravaia R. 11, Basile V.12, Marino M.13, Colantuono S.1° and Del Giacco S4°.
° Senior authors
* Corresponding author
  1. UOSD DH Internal Medicine and Gastroenterology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
  2. Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, 00168 Rome, Italy.
  3. CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
  4. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
  5. Allergy and Respiratory Diseases, IRCCS Policlinico San Martino, University of Genoa, 16132 Genoa, Italy.
  6. Allergy and Asthma Unit, Verona University Hospital, Verona, Italy.
  7. Department of Medicine, Asthma, Allergy and Clinical Immunology Section, University of Verona, Verona, Italy.
  8. Personalized Medicine, Asthma and Allergy-IRCCS Humanitas Research Hospital, Via Alessandro Manzoni, 56, 20089 Rozzano, Italy.
  9. Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy.
  10. Respiratory Medicine Unit, Policlinico ”G. Rodolico-San Marco” University Hospital, Catania, Italy.
  11. Unit of Cardiology, University Hospital Paolo Giaccone, University of Palermo.
  12. Clinical Pathology Unit and Cancer Biobank, Department of research and Advanced Technologies, IRCCS Regina Elena National Cancer Institute, Rome , Italy
  13. Sezione di Patologia Generale, Dipartimento di Medicina e Chirurugia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario ”A. Gemelli” IRCCS, Rome, Italy.

Abstract

Background: Increasing evidence are available about the presence of increased serum concentration of Immunoglobulin (Ig) Free Light Chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease, disease severity and also an alternative approach to the treatment.
Methods: We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e. erythrocyte sedimentation rate, C-reactive protein) was detectable.
Results: FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization.
Conclusions: Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for disease severity.
Keywords: biomarker, free light chains, severe asthma, type 2 inflammation.