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Elevated serum polyclonal immunoglobulin free light chains in patients with severe asthma

Affiliation
Department of Translational Medicine ,Catholic University of the Sacred Heart ,University Hospital Agostino Gemelli Foundation IRCCS ,Rome ,Italy
Basile, Umberto;
Affiliation
Pharmacology ,Faculty of Medicine ,Catholic University of the Sacred Heart ,Rome ,Italy
Santini, Giuseppe;
Affiliation
Department of Laboratory Medicine and Pathology ,S. Agostino Estense Hospital ,Modena ,Italy
Napodano, Cecilia;
Affiliation
Department of Radiological Sciences ,University Hospital Agostino Gemelli Foundation IRCCS ,Rome ,Italy
Macis, Giuseppe;
Affiliation
Clinical Pathology Unit ,San Pietro Fatebenefratelli Hospital ,Rome ,Italy
Pocino, Krizia;
Affiliation
Clinical Biochemistry Laboratory ,IRCCS ,Bambino Gesù Children’s Hospital ,Rome ,Italy
Gulli, Francesca;
Affiliation
Respiratory Unit ,S. Andrea Hospital ,University of Piemonte Orientale ,Vercelli ,Italy
Malerba, Mario;
Affiliation
National Heart and Lung Institute ,Faculty of Medicine ,Imperial College London ,London ,United Kingdom
Bush, Andrew;
Affiliation
National Heart and Lung Institute ,Faculty of Medicine ,Imperial College London ,London ,United Kingdom
Adcock, Ian M.;
Affiliation
Pharmacology ,Faculty of Medicine ,Catholic University of the Sacred Heart ,Rome ,Italy
Montuschi, Paolo

Background: Inflammation plays a pivotal role in the pathophysiology of asthma. Free light chains (FLC) can cause inflammation by mast cell antigen-activation. Serum immunoglobulin (Ig) FLC κ, but not λ, were shown elevated in adult males with asthma. We sought to investigate if serum Ig FLC concentrations are affected by asthma severity and their relationships with inflammatory outcomes. Methods: By using immunoassays, we measured serum κ and λ Ig FLCs in 24 severe persistent asthma patients, 15 patients with moderate persistent asthma, 15 steroid-naïve mild persistent asthma patients and 20 healthy control subjects in a cross-sectional observational study. Total and specific serum IgE concentrations, fractional exhaled nitric oxide (F E NO), lung function, peripheral blood eosinophils and neutrophils, and C reactive protein (CRP) were also measured. Results: Serum κ FLC concentrations were elevated in severe asthma patients compared mild asthma patients ( p < 0.05) and healthy subjects ( p < 0.05). Serum λ FLCs were higher in severe asthma patients than in healthy subjects ( p < 0.05) and correlated with blood eosinophil counts (percentage, κ: r = 0.51, p = 2.9678 −6 ; λ: r = 0.42, p = 1.7377 −4 ; absolute values, κ: r = 0.45, p = 6.1284 −5 ; λ: r = 0.38, p = 7.8261 −4 ), but not with total or specific serum IgE. In severe asthma patients, serum Ig FLC correlated with serum CRP (κ: r = 0.33; p = 0.003; λ: r = 0.38, p = 8.8305 −4 ) and blood neutrophil cell counts (percentage, κ: r = 0.31; p = 0.008; λ: r = 0.29, p = 0.01; absolute values, κ: r = 0.40; p = 3.9176 −4 ; λ: r = 0.40, p = 4.5479 −4 ), were elevated in subjects with blood eosinophilia (≥300 cells/µL) ( n = 13) compared with non-eosinophilic subjects ( n = 10) (κ: 19.2 ± 1.2 mg/L versus 12.1 ± 1.3 mg/L, p < 0.001; λ: 27.2 ± 2.6 mg/L versus 16.8 ± 2.5 mg/L, p < 0.01), but were similar in atopic ( n = 15) versus nonatopic subjects ( n = 9) (κ: p = 0.20; λ: p = 0.80). Serum FLC were negatively correlated with lung function tests, including forced expiratory volume in one second (FEV1) (κ: r = −0.33; p = 0.0034; λ: r = −0.33; p = 0.0035), and FEV 1 /forced vital capacity ratio (κ: r = −0.33; p = 0.0034; λ: r = −0.33; p = 0.0036). Conclusion: Serum Ig FLCs are elevated in severe asthma adults and might represent new surrogate markers of inflammation. The pathophysiological implications of these findings require further research. This study was approved by the ethics committee of the University Hospital Agostino Gemelli Foundation and Catholic University of the Sacred Heart (approval number P/1034/CE2012).

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License Holder: Copyright © 2023 Basile, Santini, Napodano, Macis, Pocino, Gulli, Malerba, Bush, Adcock and Montuschi.

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