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A research group based in Utrecht, in the Netherlands, has published a series of articles exploring the association and potential function of FLCs in allergic responses. The early studies (employing mouse models) reported that FLC molecules exhibiting antigen specificity could mediate mast cell-dependent hypersensitivity-like reactions [799]. Passive administration of FLCs was reported to cause mast cell activation and acute broncho-constriction, while use of a 9-mer peptide (“F991”: sequence derived from Tamm-Horsfall protein) that binds to FLC, abrogated FLC-induced symptoms [800]. The authors of this latter study also measured sFLCs in adult humans and found higher κ (but not λ) sFLC concentrations in asthmatics (n=31). For patients with hypersensitivity pneumonitis and idiopathic pulmonary fibrosis, FLC concentrations were reported to be elevated in both serum and bronchoalveolar lavage fluid with histochemistry identifying FLC-positive B-cells and plasma cells in patients’ lungs [801]. Similarly, in patients with chronic rhinosinusitis, elevated FLC concentrations were found in nasal secretions, particularly if nasal polyps were present, and histology identified FLC-positive cells in nasal polyp tissue. However, increases in sFLC concentrations were not statistically significant [802].

In a study performed by another research group, children with atopic dermatitis (n=73) were found to have significantly higher sFLC concentrations compared with controls [803]. ELISA measurement of sFLCs [804] indicated significant elevations of κ sFLC but not λ sFLC in infants with atopic dermatitis (n=25), while treatment with dietary oligosaccharides reduced concentrations of both light chains. sFLC concentrations have also been reported to be raised in infants with cows’ milk allergy [804], while in casein-sensitised mice, serum levels were raised and symptoms could be reduced by the FLC binding peptide F991 [805].