Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect

• Published in: European journal of medical genetics Vol. 59; no. 4; pp. 219 - 222
• Main Authors: Sala, Pierguido, Colatutto, Antonio, Fabbro, Dora, Mariuzzi, Laura, Marzinotto, Stefania, Toffoletto, Barbara, Perosa, Anna R, Damante, Giuseppe
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01.04.2016
• Subjects: Amino Acid Sequence - genetics; Female; Humans; Humoral immune defects; Immunity, Humoral - genetics; Immunofixation electrophoresis; Immunoglobulin kappa-Chains - genetics; Immunoglobulin lambda-Chains - genetics; Immunoglobulins; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - pathology; Kappa chains; Kappa light chain deficiency; Lambda chains; Lymphocytes - pathology; Medical Education; Middle Aged; Immunoglobulins; Kappa chains; Humoral immune defects; Kappa light chain deficiency; Lambda chains; Immunofixation electrophoresis
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2016.02.003

Abstract Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens.